An Efficacy, Safety, Tolerability, Pharmacokinetics and P... | NCT02623699 | Trialant
NCT02623699
Sponsor
Biogen
Status
Completed
Last Update Posted
Jul 28, 2023Actual
Enrollment
176Actual
Phase
Phase 3
Conditions
Amyotrophic Lateral Sclerosis
Interventions
Tofersen
Placebo
Countries
United States
Australia
Belgium
Canada
Denmark
France
Germany
Italy
Japan
Poland
South Korea
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02623699
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
233AS101
Secondary IDs
ID
Type
Description
Link
2015-004098-33
EudraCT Number
Brief Title
An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
Official Title
A Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB067 Administered to Adult Subjects With Amyotrophic Lateral Sclerosis and Confirmed Superoxide Dismutase 1 Mutation
Acronym
VALOR (Part C)
Organization
BiogenINDUSTRY
Status Module
Record Verification Date
Jul 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 20, 2016Actual
Primary Completion Date
Jul 16, 2021Actual
Completion Date
Jul 16, 2021Actual
First Submitted Date
Nov 24, 2015
First Submission Date that Met QC Criteria
Dec 3, 2015
First Posted Date
Dec 8, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
May 17, 2023
Results First Submitted that Met QC Criteria
Jul 7, 2023
Results First Posted Date
Jul 28, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jul 15, 2022
Certification/Extension First Submitted that Passed QC Review
Jul 15, 2022
Certification/Extension First Posted Date
Jul 19, 2022Actual
Last Update Submitted Date
Jul 7, 2023
Last Update Posted Date
Jul 28, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
BiogenINDUSTRY
Collaborators
Name
Class
Ionis Pharmaceuticals, Inc.
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
No
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The primary objectives of Parts A and B of this study are to evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending doses of tofersen in adults with ALS and a documented superoxide dismutase 1 (SOD1) mutation. The primary objective of Part C of this study is to evaluate the clinical efficacy of tofersen administered to adults with ALS and a confirmed SOD1 mutation.
The secondary objective of Parts A and B of this study is to evaluate the effects of tofersen on levels of total SOD1 protein in the cerebrospinal fluid (CSF). The secondary objectives of Part C are to evaluate the safety, tolerability, pharmacodynamic (PD), and biomarker effects of tofersen.
Detailed Description
This is a 3-part study to examine the efficacy, safety, tolerability, PK, and PD of tofersen. Part A is the single ascending dose (SAD) component of the study, Part B is the multiple ascending dose (MAD) component of study and Part C is the fixed dose component of the study. Hence, the overall phase of development of the study is 1/2/3.
The study completed on 16 Jul 2021. In total, the study enrolled 176 participants, of which 108 enrolled in Part C.
Conditions Module
Conditions
Amyotrophic Lateral Sclerosis
Keywords
IONIS-SOD1Rx
SOD1
ALS
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
176Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A-SAD: Combined Placebo
Placebo Comparator
Participants will be administered tofersen-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Drug: Placebo
Part A-SAD: Cohort 1: Tofersen 10 mg
Experimental
Participants will be administered tofersen 10 mg once by intrathecal bolus injection on Day 1.
Drug: Tofersen
Part A-SAD: Cohort 2: Tofersen 20 mg
Experimental
Participants will be administered tofersen 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
Drug: Tofersen
Part A-SAD: Cohort 3: Tofersen 40 mg
Experimental
Participants will be administered tofersen 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Drug: Tofersen
Part A-SAD: Cohort 4: Tofersen 60 mg
Experimental
Participants will be administered tofersen 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Tofersen
Drug
Administered as specified in the treatment arm.
Part A-SAD: Cohort 1: Tofersen 10 mg
Part A-SAD: Cohort 2: Tofersen 20 mg
Part A-SAD: Cohort 3: Tofersen 40 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Parts A and B: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Part A: First dose up to Day 63; Part B: First dose up to Day 289
Parts A and B: Number of Participants With Clinically Significant Laboratory Abnormalities
Clinical laboratory assessments included hematology, chemistry, and urinalysis.
Part A: Up to Day 57; Part B: Up to Day 169
Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities
The criteria for clinically significant vital sign abnormalities include: Temperature: >38 degree Celsius (°C) or an increase from baseline of ≥1°C; Pulse: >120 beats per minute (bpm) or an increase from baseline of >20 bpm, <50 bpm or a decrease from baseline of >20 bpm; Systolic blood pressure (BP): >180 mmHg or an increase from baseline of >40 mmHg, <90 mmHg or a decrease from baseline of >30 mmHg; Diastolic BP: >105 mmHg or an increase from baseline of >30 mmHg, <50 mmHg or a decrease from baseline of >20 mmHg.
Part A: Up to Day 57; Part B: Up to Day 169
Parts A and B: Number of Participants With Clinically Significant Physical Examination Abnormalities
Clinically significant physical examination abnormalities included weight decreased.
Part A: Up to Day 57; Part B: Up to Day 169
Secondary Outcomes
Measure
Description
Time Frame
Part B: CSF Levels of Total SOD1 Protein Concentration Ratio to Baseline
Total CSF SOD1 protein ratio to baseline was calculated.
Day 85
Part C: CSF Levels of Total SOD1 Protein Concentration Ratio to Baseline
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria: Part A and B
Weakness attributable to ALS and documented SOD1 mutation at Screening Visit 2.
A forced vital capacity (FVC) ≥50% of predicted value as adjusted for sex, age, and height (from the sitting position). Participants with stable FVC <50% but ≥45%, whose FVC has not declined by more than 5% in the last 6 months may be considered for inclusion, at the discretion of the Investigator.
If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
Key Exclusion Criteria: Part A and B
History of or positive test result for human immunodeficiency virus.
History of, or positive test result at Screening, for hepatitis C virus antibody.
Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive hepatitis B surface antibody immunoglobulin G, and positive HBcAb) or vaccination (defined as positive anti-HBs) are eligible to participate in the study.
Treatment with another investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering ribonucleic acid, stem cell therapy, or gene therapy is allowed.
Current enrollment in any other interventional study.
Current or recent (within 1 month) use, or anticipated need, in the opinion of the Investigator, of copper (II) (diacetyl-bis (N4-methylthiosemicarbazone)) or pyrimethamine.
Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period.
Key Inclusion Criteria: Part C
Weakness attributable to ALS and confirmed SOD1 mutation at Screening Visit.
If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
If taking edaravone, participant must have initiated edaravone ≥60 days (2 treatment cycles) prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of this study.
Medically able to undergo the study procedures and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
Key Exclusion Criteria: Part C
History of or positive test result for human immunodeficiency virus.
Current hepatitis C infection (defined as positive hepatitis C virus [HCV] antibody and detectable HCV ribonucleic acid [RNA]). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (United States Centers for Disease Control and Prevention).
Current hepatitis B infection (defined as positive for HBsAg and/or anti-HBc). participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.
Current enrollment in any other interventional study.
Current or recent (within 1 month) use, or anticipated need, in the opinion of the Investigator, of copper (II) (diacetyl-bis(N4-methylthiosemicarbazone)) or pyrimethamine.
Current or anticipated need, in the opinion of the Investigator, of a DPS during the study period.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study included SAD (Part A), MAD (Part B) and pivotal portions (Part C). Total 176 participants were randomized: 20 into Part A, 50 into Part B including 2 participants who completed Part A, were randomized in Part B after 12-week washout period, hence 2 participants were analysed in both Parts A, B (for total of 68 in Parts A, B), Part C randomized 108 participants.
Recruitment Details
Participants were enrolled at the investigative sites in the Belgium, Canada, Denmark, France, Germany, Italy, Japan, United Kingdom, and the United States from 20 January 2016 to 16 July 2021.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
Participants will be administered tofersen-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Drug: Placebo
Part B-MAD: Cohort 5: Tofersen 20 mg
Experimental
Participants will be administered tofersen 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
Drug: Tofersen
Part B-MAD: Cohort 6: Tofersen 40 mg
Experimental
Participants will be administered tofersen 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
Drug: Tofersen
Part B-MAD: Cohort 7: Tofersen 60 mg
Experimental
Participants will be administered tofersen 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
Drug: Tofersen
Part B-MAD: Cohort 8: Tofersen 100 mg
Experimental
Participants will be administered tofersen 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Drug: Tofersen
Part C-Pivotal: Placebo
Placebo Comparator
Participants will be administered tofersen-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Drug: Placebo
Part C-Pivotal: Tofersen 100 mg
Experimental
Participants will be administered tofersen 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Drug: Tofersen
Part A-SAD: Cohort 4: Tofersen 60 mg
Part B-MAD: Cohort 5: Tofersen 20 mg
Part B-MAD: Cohort 6: Tofersen 40 mg
Part B-MAD: Cohort 7: Tofersen 60 mg
Part B-MAD: Cohort 8: Tofersen 100 mg
Part C-Pivotal: Tofersen 100 mg
BIIB067
QALSODY
Placebo
Drug
Administered as specified in the treatment arm.
Part A-SAD: Combined Placebo
Part B-MAD: Combined Placebo
Part C-Pivotal: Placebo
Parts A and B: Number of Participants With Clinically Significant Neurological Examination Abnormalities
Clinically significant neurological examination abnormalities included hyporeflexia.
Part A: Up to Day 57; Part B: Up to Day 169
Parts A and B: Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Abnormalities
Part A: Up to Day 57; Part B: Up to Day 169
Parts A and B: PK Parameter of BIIB067 in Plasma: Maximum Observed Concentration (Cmax)
Part A: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1; Part B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1 and 1, 2, 4, 6 hrs post-dose on Day 85
Parts A and B: PK Parameter of BIIB067 in Plasma: Time to Reach Maximum Observed Concentration (Tmax)
Part A: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1; Part B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1 and 1, 2, 4, 6 hrs post-dose on Day 85
Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
Parts A and B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1
Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast)
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Parts A and B: PK Parameter of BIIB067 in Plasma: Apparent Terminal Elimination Half-life (t1/2)
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Parts A and B: PK Parameters of BIIB067 in CSF Levels: Terminal Elimination Half-life (t1/2)
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
Part C: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score at Week 28
The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 (no function) to 4 (full function), for a total possible score of 48. Scores decline with disease progression. ALSFRS-R scores calculated at diagnosis can be compared to scores throughout time to determine the speed of progression. Higher scores represent better function, negative change from baseline indicates disease progression.
Baseline, Week 28 (Day 197)
Total CSF SOD1 protein ratio to baseline was calculated and LS Geometric Mean ratio to baseline was reported.
Week 28 (Day 197)
Part C: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
NfL is a biomarker whose concentration was assessed in plasma. Plasma NfL ratio to baseline was calculated.
Baseline, Day 197 (Week 28)
Part C: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC) at Week 28
Vital capacity was measured by means of an SVC test, administered in the upright position.
Baseline, Week 28 (Day 197)
Part C: Change From Baseline in Handheld Dynamometry (HHD) Megascore as Measured by the HHD Device at Week 28
Quantitative muscle strength was evaluated using HHD, which tests isometric strength of multiple muscles using standard participant positioning. Sixteen muscle groups were evaluated in both upper and lower extremities. The muscle strength values were normalized to Z scores as (post-baseline measurements - mean)/SD and averaged to provide HHD overall megascore. The overall megascore was created by averaging all eight bilateral measurement Z scores, if no more than 10 (≤ 10) measures are missing. A negative change from baseline indicated decreased muscle strength.
Baseline, Week 28 (Day 197)
Part C: Time to Death or Permanent Ventilation
Time to Death or Permanent Ventilation is defined as the time to the earliest occurrence of one of the following events that were adjudicated by an independent committee: Death; Permanent ventilation (≥22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥21 consecutive days).
Baseline up to Week 28 (Day 197)
Part C: Time to Death
Baseline up to Week 28 (Day 197)
Part C: Number of Participants Experiencing AEs and SAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
First dose up to Day 236
La Jolla
California
92093
United States
California Pacific Medical Center
San Francisco
California
94115
United States
Mayo Clinic in Florida
Jacksonville
Florida
32224
United States
University of Miami School of Medicine
Miami
Florida
33136
United States
Bioclinica Research
Orlando
Florida
32806
United States
Emory University Hospital
Atlanta
Georgia
30322
United States
Northwestern University Feinberg School of Medicine
Chicago
Illinois
60611
United States
Johns Hopkins University
Baltimore
Maryland
21287
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Henry Ford Hospital
Detroit
Michigan
48202
United States
Mayo Clinic - Rochester
Rochester
Minnesota
55905
United States
Washington University School of Medicine
St Louis
Missouri
63110
United States
Neurology Associates, P.C.
Lincoln
Nebraska
68506
United States
Columbia University Medical Center
New York
New York
10032
United States
The Cleveland Clinic Foundation
Cleveland
Ohio
44106
United States
Providence ALS Center
Portland
Oregon
97213
United States
University of Pennsylvania
Philadelphia
Pennsylvania
19104
United States
New Orleans Center for Clinical Research/Volunteer Research Group, an AMR Company
Knoxville
Tennessee
37920
United States
Methodist Neurological Institute
Houston
Texas
77030
United States
Westmead Hospital
Westmead
New South Wales
2145
Australia
UZ Leuven
Leuven
3000
Belgium
University of Calgary - Health Sciences Centre
Calgary
Alberta
T2N 1N4
Canada
Research Site
Edmonton
Alberta
T6G 2G3
Canada
Sunnybrook Health Sciences Centre
Toronto
Ontario
M4N 3M5
Canada
Montreal Neurological Institute
Montreal
Quebec
H3A 2B4
Canada
Bispebjerg Hospital
Copenhagen
2400
Denmark
Hopital Pitie Salpetriere
Paris
75651
France
University of Ulm
Ulm
Baden-Wurttemberg
89081
Germany
ALS Center - Dept. of Neuroscience "Rita Levi Montalcini", University of Turin
Torino
10126
Italy
The University of Tokyo Hospital
Bunkyō City
Japan
Research Site
Fukuoka
Japan
Research Site
Kagoshima
Japan
Research Site
Shinjuku-ku
Japan
Research Site
Suita-Shi
Japan
Research Site
Warsaw
01684
Poland
Research Site
Yangsan
Gyeongsangnam-do
50612
South Korea
Research Site
Seoul
04763
South Korea
Research Site
London
Greater London
SE5 9RS
United Kingdom
Research Site
Sheffield
South Yorkshire
S10 2HQ
United Kingdom
Derived
Miller TM, Cudkowicz ME, Shaw PJ, Genge A, Sobue G, Bucelli RC, Chio A, Van Damme P, Ludolph AC, Glass JD, Andrews JA, Babu S, Benatar M, McDermott CJ, Salachas F, Bruneteau G, Al-Chalabi A, Amorin M, Nestorov I, Graham D, Lin L, Sun P, McNeill M, Malek S, Inra J, Garafalo S, Fradette S; VALOR and OLE Working Group. Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis. JAMA Neurol. 2026 Feb 1;83(2):115-125. doi: 10.1001/jamaneurol.2025.4946.
Miller TM, Cudkowicz ME, Genge A, Shaw PJ, Sobue G, Bucelli RC, Chio A, Van Damme P, Ludolph AC, Glass JD, Andrews JA, Babu S, Benatar M, McDermott CJ, Cochrane T, Chary S, Chew S, Zhu H, Wu F, Nestorov I, Graham D, Sun P, McNeill M, Fanning L, Ferguson TA, Fradette S; VALOR and OLE Working Group. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2022 Sep 22;387(12):1099-1110. doi: 10.1056/NEJMoa2204705.
Miller T, Cudkowicz M, Shaw PJ, Andersen PM, Atassi N, Bucelli RC, Genge A, Glass J, Ladha S, Ludolph AL, Maragakis NJ, McDermott CJ, Pestronk A, Ravits J, Salachas F, Trudell R, Van Damme P, Zinman L, Bennett CF, Lane R, Sandrock A, Runz H, Graham D, Houshyar H, McCampbell A, Nestorov I, Chang I, McNeill M, Fanning L, Fradette S, Ferguson TA. Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020 Jul 9;383(2):109-119. doi: 10.1056/NEJMoa2003715.
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
FG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
FG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
FG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
FG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
FG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
FG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and pharmacokinetic (PK) review of Cohort 5.
FG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and superoxide dismutase 1 (SOD1) pharmacodynamic (PD) review of Cohort 6.
FG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
FG010
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
FG011
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
FG0005 subjects
FG0013 subjects
FG0023 subjects
FG0033 subjects
FG0046 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
COMPLETED
FG0005 subjects
FG0012 subjects
FG0023 subjects
FG0033 subjects
FG0046 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Type
Comment
Reasons
Consent Withdrawn
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Part B (Up to 289 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjectsParticipants who completed Part A did not enter Part B of the study.
FG0010 subjectsParticipants who completed Part A did not enter Part B of the study.
FG0020 subjectsParticipants who completed Part A did not enter Part B of the study.
FG0030 subjectsParticipants who completed Part A did not enter Part B of the study.
FG0040 subjectsParticipants who completed Part A did not enter Part B of the study.
FG00512 subjectsStarted indicates the number of participants who were enrolled into Part B of the study.
FG00610 subjectsStarted indicates the number of participants who were enrolled into Part B of the study.
FG0079 subjectsStarted indicates the number of participants who were enrolled into Part B of the study.
FG0089 subjectsStarted indicates the number of participants who were enrolled into Part B of the study.
FG00910 subjectsStarted indicates the number of participants who were enrolled into Part B of the study.
FG0100 subjects
FG0110 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part C (Up to 236 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjectsParticipants who completed Part B did not enter Part C of the study.
FG0060 subjectsParticipants who completed Part B did not enter Part C of the study.
FG0070 subjectsParticipants who completed Part B did not enter Part C of the study.
FG0080 subjectsParticipants who completed Part B did not enter Part C of the study.
FG0090 subjectsParticipants who completed Part B did not enter Part C of the study.
FG01036 subjectsStarted indicates the number of participants who were enrolled into Part C of the study.
FG01172 subjectsStarted indicates the number of participants who were enrolled into Part C of the study.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Intention-to-Treat (ITT) populations for parts A, B, and C included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Parts A, B, and C respectively. The demographics data reported for Part B arm groups included only the unique participants who were enrolled directly into Part B of the study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
BG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
BG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
BG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
BG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
BG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
BG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
BG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
BG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
BG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
BG010
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
BG011
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
BG012
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0005
BG0013
BG0023
BG0033
BG0046
BG00512
BG0069
BG0078
BG0089
BG00910
BG01036
BG01172
BG012176
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG0005
ParticipantsBG0013
ParticipantsBG0023
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0005
ParticipantsBG0013
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0005
ParticipantsBG0013
ParticipantsBG002
Race/Ethnicity, Customized
Not reported indicates that race data was not reported due to confidentiality regulations.
ALSFRS-R measures respiratory, bulbar function, gross, and fine motor skills. 12 questions, each scored from 0-4 (no-full function), for a total score of 48. Scores decline with disease progression. Higher scores represent better function.
Modified ITT (mITT) population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG001
Cerebrospinal Fluid (CSF) Levels of Total SOD1 Protein Concentration
Pharmacodynamic (PD) population is subset of ITT population with at least 1 post-dose PD measurement in Part B. mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part B and C arms groups.
Geometric Mean
Full Range
nanograms per milliliter (ng/mL)
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
Percentage Predicted Slow Vital Capacity (SVC)
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
Mean
Standard Deviation
percent predicted
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
ParticipantsBG002
Handheld Dynamometry (HHD) Megascore as Measured by the HHD Device
16 muscle groups were evaluated in upper, lower extremities. Muscle strength values were normalized to Z scores as (post-baseline measurements - mean)/standard deviation (SD), averaged to provide HHD overall megascore.
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG001
Neurofilament Light Chain (NfL) Concentration in Plasma
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment. This measure was only analyzed for Part C arms groups.
Geometric Mean
Full Range
picograms per mL (pg/mL)
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Parts A and B: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Posted
Count of Participants
Participants
Part A: First dose up to Day 63; Part B: First dose up to Day 289
ID
Title
Description
OG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
OG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0005
OG0013
OG0023
OG003
Title
Denominators
Categories
AEs
Title
Measurements
OG0002
OG0012
OG0023
OG003
Primary
Parts A and B: Number of Participants With Clinically Significant Laboratory Abnormalities
Clinical laboratory assessments included hematology, chemistry, and urinalysis.
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Posted
Count of Participants
Participants
Part A: Up to Day 57; Part B: Up to Day 169
ID
Title
Description
OG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
OG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Primary
Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities
The criteria for clinically significant vital sign abnormalities include: Temperature: >38 degree Celsius (°C) or an increase from baseline of ≥1°C; Pulse: >120 beats per minute (bpm) or an increase from baseline of >20 bpm, <50 bpm or a decrease from baseline of >20 bpm; Systolic blood pressure (BP): >180 mmHg or an increase from baseline of >40 mmHg, <90 mmHg or a decrease from baseline of >30 mmHg; Diastolic BP: >105 mmHg or an increase from baseline of >30 mmHg, <50 mmHg or a decrease from baseline of >20 mmHg.
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Posted
Count of Participants
Participants
Part A: Up to Day 57; Part B: Up to Day 169
ID
Title
Description
OG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
OG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Primary
Parts A and B: Number of Participants With Clinically Significant Physical Examination Abnormalities
Clinically significant physical examination abnormalities included weight decreased.
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Posted
Count of Participants
Participants
Part A: Up to Day 57; Part B: Up to Day 169
ID
Title
Description
OG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
OG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Primary
Parts A and B: Number of Participants With Clinically Significant Neurological Examination Abnormalities
Clinically significant neurological examination abnormalities included hyporeflexia.
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Posted
Count of Participants
Participants
Part A: Up to Day 57; Part B: Up to Day 169
ID
Title
Description
OG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
OG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Primary
Parts A and B: Number of Participants With Clinically Significant 12-lead Electrocardiograms (ECGs) Abnormalities
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B.
Posted
Count of Participants
Participants
Part A: Up to Day 57; Part B: Up to Day 169
ID
Title
Description
OG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
OG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
Primary
Parts A and B: PK Parameter of BIIB067 in Plasma: Maximum Observed Concentration (Cmax)
PK population is the subset of the ITT population (all randomized participants who received at least 1 dose or a part of 1 dose of study treatment) of participants with at least 1 post-dose PK measurement in Part A or B. Data was not collected for participants on Day 85 for Part A of the study.
Posted
Geometric Mean
Full Range
ng/mL
Part A: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1; Part B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1 and 1, 2, 4, 6 hrs post-dose on Day 85
ID
Title
Description
OG000
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG001
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG002
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG003
Part A-SAD: Cohort 4: BIIB067 60 mg
Primary
Parts A and B: PK Parameter of BIIB067 in Plasma: Time to Reach Maximum Observed Concentration (Tmax)
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B. Data was not collected for participants on Day 85 for Part A of the study.
Posted
Geometric Mean
Full Range
hours
Part A: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1; Part B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1 and 1, 2, 4, 6 hrs post-dose on Day 85
ID
Title
Description
OG000
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG001
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG002
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG003
Part A-SAD: Cohort 4: BIIB067 60 mg
Primary
Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h)
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Posted
Geometric Mean
Full Range
hour*ng/mL
Parts A and B: Pre-dose, 1, 2, 4, 6 hrs post-dose on Day 1
ID
Title
Description
OG000
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG001
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG002
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG003
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Primary
Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Posted
Mean
Standard Deviation
hour*ng/mL
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
ID
Title
Description
OG000
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG001
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG002
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG003
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Primary
Parts A and B: PK Parameter of BIIB067 in Plasma: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast)
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Posted
Mean
Standard Deviation
hour*ng/mL
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
ID
Title
Description
OG000
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG001
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG002
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG003
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Primary
Parts A and B: PK Parameter of BIIB067 in Plasma: Apparent Terminal Elimination Half-life (t1/2)
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Posted
Median
Inter-Quartile Range
hours
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
ID
Title
Description
OG000
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG001
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG002
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG003
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Primary
Parts A and B: PK Parameters of BIIB067 in CSF Levels: Terminal Elimination Half-life (t1/2)
PK population is the subset of the ITT population with at least 1 post-dose PK measurement in Part A or B.
Posted
Median
Inter-Quartile Range
hours
Part A: Pre-dose Day 1, Days 29 and 57; Part B: Pre-dose Days 1, 15, 29, 57 and 85; Day 106 and 169
ID
Title
Description
OG000
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
OG001
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG002
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG003
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
Primary
Part C: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Total Score at Week 28
The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 (no function) to 4 (full function), for a total possible score of 48. Scores decline with disease progression. ALSFRS-R scores calculated at diagnosis can be compared to scores throughout time to determine the speed of progression. Higher scores represent better function, negative change from baseline indicates disease progression.
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Posted
Least Squares Mean
Standard Error
score on scale
Baseline, Week 28 (Day 197)
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Secondary
Part B: CSF Levels of Total SOD1 Protein Concentration Ratio to Baseline
Total CSF SOD1 protein ratio to baseline was calculated.
PD population is the subset of the ITT population with at least 1 post-dose PD measurement in Part B.
Posted
Geometric Mean
95% Confidence Interval
ratio
Day 85
ID
Title
Description
OG000
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG001
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG002
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG003
Secondary
Part C: CSF Levels of Total SOD1 Protein Concentration Ratio to Baseline
Total CSF SOD1 protein ratio to baseline was calculated and LS Geometric Mean ratio to baseline was reported.
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Posted
Geometric Least Squares Mean
95% Confidence Interval
ratio
Week 28 (Day 197)
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Units
Counts
Participants
Secondary
Part C: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
NfL is a biomarker whose concentration was assessed in plasma. Plasma NfL ratio to baseline was calculated.
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Posted
Geometric Least Squares Mean
95% Confidence Interval
ratio
Baseline, Day 197 (Week 28)
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Units
Counts
Participants
Secondary
Part C: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC) at Week 28
Vital capacity was measured by means of an SVC test, administered in the upright position.
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Posted
Least Squares Mean
Standard Error
percent predicted
Baseline, Week 28 (Day 197)
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Units
Counts
Participants
Secondary
Part C: Change From Baseline in Handheld Dynamometry (HHD) Megascore as Measured by the HHD Device at Week 28
Quantitative muscle strength was evaluated using HHD, which tests isometric strength of multiple muscles using standard participant positioning. Sixteen muscle groups were evaluated in both upper and lower extremities. The muscle strength values were normalized to Z scores as (post-baseline measurements - mean)/SD and averaged to provide HHD overall megascore. The overall megascore was created by averaging all eight bilateral measurement Z scores, if no more than 10 (≤ 10) measures are missing. A negative change from baseline indicated decreased muscle strength.
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 28 (Day 197)
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Secondary
Part C: Time to Death or Permanent Ventilation
Time to Death or Permanent Ventilation is defined as the time to the earliest occurrence of one of the following events that were adjudicated by an independent committee: Death; Permanent ventilation (≥22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥21 consecutive days).
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Posted
Median
95% Confidence Interval
days
Baseline up to Week 28 (Day 197)
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Secondary
Part C: Time to Death
mITT population included all participants who met the prognostic enrichment criteria for rapid disease progression in Part C who were randomized and received at least 1 dose of study treatment.
Posted
Median
95% Confidence Interval
days
Baseline up to Week 28 (Day 197)
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Units
Counts
Participants
OG000
Secondary
Part C: Number of Participants Experiencing AEs and SAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Safety population included all participants in Part C who were randomized and received at least one dose of study treatment.
Posted
Count of Participants
Participants
First dose up to Day 236
ID
Title
Description
OG000
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
OG001
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
Time Frame
Part A: First dose up to Day 63; Part B: First dose up to Day 289; Part C: First dose up to Day 236
Description
Safety population included all randomized participants who received at least 1 dose or a part of 1 dose of study treatment (BIIB067 or placebo) in Part A or B. Safety population included all participants in Part C who were randomized and received at least one dose of study treatment. MedDRA version for Parts A and B: 22.0, Part C: 24.0
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A-SAD: Combined Placebo
Participants were administered BIIB067-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively.
0
5
0
5
2
5
EG001
Part A-SAD: Cohort 1: BIIB067 10 mg
Participants were administered BIIB067 10 mg once by intrathecal bolus injection on Day 1.
0
3
0
3
2
3
EG002
Part A-SAD: Cohort 2: BIIB067 20 mg
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
0
3
0
3
3
3
EG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
0
3
0
3
3
3
EG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
0
6
0
6
6
6
EG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
1
12
2
12
11
12
EG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
1
10
2
10
10
10
EG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
0
9
1
9
9
9
EG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
1
9
2
9
9
9
EG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
0
10
0
10
10
10
EG010
Part C-Pivotal: Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
0
36
5
36
34
36
EG011
Part C-Pivotal: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection.
1
72
13
72
68
72
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Cardiac failure congestive
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG0030 affected3 at risk
EG0040 affected6 at risk
EG0050 affected12 at risk
EG0061 affected10 at risk
EG0070 affected9 at risk
EG0080 affected9 at risk
EG0090 affected10 at risk
EG0100 affected36 at risk
EG0111 affected72 at risk
Faecaloma
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypothermia
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Impaired self-care
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Respiratory complication associated with device
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Myelitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fibula fracture
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Meningitis chemical
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Loss of consciousness
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lumbar radiculopathy
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Myelitis transverse
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Acute respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Atelectasis
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pneumonia aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Csf protein increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Csf white blood cell count increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Eosinophilia
Blood and lymphatic system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG0030 affected3 at risk
EG0040 affected6 at risk
EG0050 affected12 at risk
EG0060 affected10 at risk
EG0070 affected9 at risk
EG0080 affected9 at risk
EG0091 affected10 at risk
EG0100 affected36 at risk
EG0110 affected72 at risk
Atrial fibrillation
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gastrointestinal disorder
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gingival pain
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lip swelling
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Salivary hypersecretion
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Asthenia
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Chest pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fatigue
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Feeling abnormal
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Feeling hot
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Influenza like illness
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Infusion site bruising
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Infusion site swelling
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Oedema peripheral
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pain
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Peripheral swelling
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pyrexia
General disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dust allergy
Immune system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Ear infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Fungal skin infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gastric infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hordeolum
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Influenza
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Labyrinthitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Systemic viral infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Accident
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Foot fracture
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Head injury
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Joint injury
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Musculoskeletal procedural complication
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Nasal injury
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Post lumbar puncture syndrome
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Post procedural complication
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Post procedural contusion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Post procedural discomfort
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Post-traumatic pain
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Procedural anxiety
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Procedural complication
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Procedural dizziness
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Procedural headache
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Procedural nausea
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Subcutaneous haematoma
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Tibia fracture
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Vaccination complication
Injury, poisoning and procedural complications
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Blood phosphorus decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Csf protein increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Csf white blood cell count increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Csf white blood cell count positive
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Urine output decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Weight decreased
Investigations
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Diabetes mellitus inadequate control
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Type 2 diabetes mellitus
Metabolism and nutrition disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Muscle tightness
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dysaesthesia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Headache
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0022 affected3 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hyporeflexia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Migraine
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Muscle contractions involuntary
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Muscle spasticity
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Nerve compression
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Peroneal nerve palsy
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pleocytosis
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Depression
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Choking
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Respiratory symptom
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sleep apnoea syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sputum discoloured
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Upper respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Upper-airway cough syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Cold sweat
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Decubitus ulcer
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dermatitis allergic
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Miliaria
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Skin disorder
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Skin plaque
Skin and subcutaneous tissue disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Flushing
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypertension
Vascular disorders
MedDRA 24.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0005
OG0013
OG0023
OG0033
OG0046
OG00512
OG00610
OG0079
OG0089
OG00910
Title
Denominators
Categories
Pleocytosis
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0062
OG0071
OG0080
OG0090
Eosinophilia
Title
Measurements
OG0000
OG0010
OG0020
OG003
Blood Phosphorus Decreased
Title
Measurements
OG0000
OG0010
OG0020
OG003
CSF Protein Increased
Title
Measurements
OG0000
OG0010
OG0020
OG003
CSF White Blood Cell Count Increased
Title
Measurements
OG0000
OG0010
OG0020
OG003
CSF White Blood Cell Count Positive
Title
Measurements
OG0000
OG0010
OG0020
OG003
Gamma-Glutamyltransferase Increased
Title
Measurements
OG0000
OG0010
OG0020
OG003
Urine Output Decreased
Title
Measurements
OG0000
OG0010
OG0020
OG003
Participants were administered BIIB067 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1.
OG003
Part A-SAD: Cohort 3: BIIB067 40 mg
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0005
OG0013
OG0023
OG0033
OG0046
OG00512
OG00610
OG0079
OG0089
OG00910
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
OG0090
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0005
OG0013
OG0023
OG0033
OG0046
OG00512
OG00610
OG0079
OG0089
OG00910
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0051
OG0060
OG0070
OG0080
OG0091
Participants were administered BIIB067 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2.
OG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0005
OG0013
OG0023
OG0033
OG0046
OG00512
OG00610
OG0079
OG0089
OG00910
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0041
OG0050
OG0060
OG0070
OG0080
OG0090
OG004
Part A-SAD: Cohort 4: BIIB067 60 mg
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG005
Part B-MAD: Combined Placebo
Participants were administered BIIB067-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG006
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG007
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG008
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG009
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0005
OG0013
OG0023
OG0033
OG0046
OG00512
OG00610
OG0079
OG0089
OG00910
Title
Denominators
Categories
Maximum Increase From Baseline QTcF > 30 to 60 ms
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0053
OG0061
OG0072
OG0082
OG0093
Maximum Post-baseline QTcF > 480 to 500 ms
Title
Measurements
OG0000
OG0010
OG0020
OG003
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG004
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG005
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG006
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG007
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0036
OG00410
OG0059
OG0069
OG00710
Title
Denominators
Categories
Day 1
ParticipantsOG0003
ParticipantsOG0013
ParticipantsOG0023
ParticipantsOG0036
ParticipantsOG00410
ParticipantsOG0059
ParticipantsOG0069
ParticipantsOG00710
Title
Measurements
OG00064.94(38.8 to 159.0)
OG00175.06(43.0 to 144.0)
OG002202.09(174.0 to 236.0)
OG003
Day 85
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Participants were administered BIIB067 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3.
OG004
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG005
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG006
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG007
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0036
OG00410
OG0059
OG0069
OG00710
Title
Denominators
Categories
Day 1
ParticipantsOG0003
ParticipantsOG0013
ParticipantsOG0023
ParticipantsOG0036
ParticipantsOG00410
ParticipantsOG0059
ParticipantsOG0069
ParticipantsOG00710
Title
Measurements
OG0004.58(4.0 to 6.0)
OG0014.16(2.0 to 6.0)
OG0026.00(6.0 to 6.0)
OG003
Day 85
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
OG004
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG005
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG006
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG007
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0036
OG00410
OG0059
OG0069
OG00710
Title
Denominators
Categories
Title
Measurements
OG000879.86(550.8 to 1989.5)
OG0011027.18(879.2 to 1263.2)
OG0022873.77(2347.2 to 3543.4)
OG0035196.11(2410.2 to 10977.3)
OG0041009.85(372.8 to 2192.3)
OG0052875.13(541.1 to 6984.8)
OG0064289.16(1347.6 to 10637.1)
OG00711344.47(4025.5 to 26143.0)
OG004
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG005
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG006
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG007
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0036
OG00410
OG0059
OG0069
OG00710
Title
Denominators
Categories
Title
Measurements
OG000NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG001NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG002NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG003NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG004NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG005NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG006NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG007NA± NAData is not available as the concentration values were below the level of quantification and could not be quantified to estimate the AUC0-infinity values.
OG004
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG005
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG006
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG007
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0036
OG00410
OG0059
OG0069
OG00710
Title
Denominators
Categories
Title
Measurements
OG000NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG001NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG002NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG003NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG004NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG005NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG006NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG007NA± NADue to the large number of values below the level of quantification at various times, the last measurable concentration would have varied across individuals which makes this parameter not useful.
OG004
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG005
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG006
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG007
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0036
OG00410
OG0059
OG0069
OG00710
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG001NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG002NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG003NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG004NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG005NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG006NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG007NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the apparent terminal t1/2 values.
OG004
Part B-MAD: Cohort 5: BIIB067 20 mg
Participants were administered BIIB067 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection.
OG005
Part B-MAD: Cohort 6: BIIB067 40 mg
Participants were administered BIIB067 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5.
OG006
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG007
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0036
OG00410
OG0059
OG0069
OG00710
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
OG001NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
OG002NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
OG003NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
OG004NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
OG005NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
OG006NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
OG007NA(NA to NA)Data is not available as the concentration values were below the level of quantification and could not be quantified to estimate the terminal t1/2 values.
Units
Counts
Participants
OG00021
OG00139
Title
Denominators
Categories
Title
Measurements
OG000-8.1± 1.79
OG001-7.0± 1.42
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Joint rank test combining function and mortality were used for statistical inference and the estimates were from the Analysis of covariance (ANCOVA) for change from baseline. Multiple imputation was used to handle missing data for withdrawals other than death in the joint rank analysis. Multiple imputation was used to handle all missing data in the ANCOVA for change from baseline.
Joint rank
= 0.9689
Joint rank p-value was calculated from ANCOVA model which included treatment as fixed effect, adjusts for covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, and use of riluzole or edaravone.
least square (LS) mean difference
1.2
Standard Error of the Mean
2.22
2-Sided
95
-3.19
5.53
ANCOVA model included treatment as a fixed effect, adjusts for the covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, and use of riluzole or edaravone.
Superiority
Part B-MAD: Cohort 7: BIIB067 60 mg
Participants were administered BIIB067 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6.
OG004
Part B-MAD: Cohort 8: BIIB067 100 mg
Participants were administered BIIB067 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7.
Units
Counts
Participants
OG00012
OG00110
OG0029
OG0038
OG00410
Title
Denominators
Categories
Title
Measurements
OG0000.97(0.83 to 1.13)
OG0010.99(0.83 to 1.18)
OG0020.73(0.61 to 0.87)
OG0030.79(0.66 to 0.94)
OG0040.64(0.55 to 0.76)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Wilcoxon rank sum test
< 0.0001
Difference in LS geometric mean ratio
0.67
2-Sided
95
0.53
0.84
Superiority
OG000
OG002
Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Wilcoxon rank sum test
=0.0002
Difference in LS geometric mean ratio
0.75
2-Sided
95
0.60
0.95
Superiority
OG000
OG003
Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Wilcoxon rank sum test
=0.0641
Difference in LS geometric mean ratio
0.81
2-Sided
95
0.65
1.02
Superiority
OG000
OG004
Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
Wilcoxon rank sum test
<0.0001
Difference in LS geometric mean ratio
0.67
2-Sided
95
0.53
0.84
Superiority
OG00021
OG00139
Title
Denominators
Categories
Title
Measurements
OG0001.16(0.96 to 1.40)
OG0010.71(0.62 to 0.83)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The ANCOVA model included covariates for the corresponding baseline value i.e. log value, baseline disease duration since symptom onset, and use of riluzole or edaravone. Multiple imputation was used to handle missing data for withdrawals. Difference in LS geometric mean ratio to baseline (BIIB067:Placebo) was calculated.
ANCOVA
< 0.0001
The analysis was based on ANCOVA model with natural log transformed data. P-value for this secondary outcome measure (OM) is nominal as statistical significance was not met on the primary OM.
Difference in LS geometric mean ratio
0.62
2-Sided
95
0.49
0.78
Superiority
OG00021
OG00139
Title
Denominators
Categories
Title
Measurements
OG0001.20(0.94 to 1.52)
OG0010.40(0.33 to 0.48)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference in LS geometric mean ratio (BIIB067:Placebo) was calculated.
ANCOVA
P-value for this secondary OM is nominal as statistical significance was not met on the primary OM.
< 0.0001
The analysis was based on ANCOVA model with natural log transformed data. The model included covariates for the corresponding baseline value i.e. log value, baseline disease duration since symptom onset, and use of riluzole or edaravone.
Difference in LS geometric mean ratio
0.33
2-Sided
95
0.25
0.45
Superiority
OG00021
OG00139
Title
Denominators
Categories
Title
Measurements
OG000-22.20± 4.771
OG001-14.31± 3.557
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Joint rank test combining function and mortality were used for statistical inference and the estimates were from the ANCOVA for change from baseline. Multiple imputation was used to handle missing data for withdrawals other than death in the joint rank analysis. Multiple imputation was used to handle all missing data in the ANCOVA for change from baseline.
Joint rank
P-value for this secondary OM is nominal as statistical significance was not met on the primary OM.
= 0.3233
Joint rank p-value was calculated from ANCOVA model which included treatment as fixed effect, adjusts for covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, baseline SVC, and use of riluzole or edaravone.
LS mean difference
7.90
Standard Error of the Mean
5.829
2-Sided
95
-3.528
19.322
ANCOVA model included treatment as a fixed effect, adjusts for the covariates: Baseline disease duration since symptom onset, baseline ALSFRS-R total score, baseline SVC, and use of riluzole or edaravone.
Superiority
Units
Counts
Participants
OG00021
OG00139
Title
Denominators
Categories
Title
Measurements
OG000-0.37± 0.096
OG001-0.34± 0.073
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value for this secondary OM is nominal as statistical significance was not met on the primary OM.
= 0.8390
ANCOVA model included treatment as fixed effect and adjusts for following covariates: Baseline disease duration since symptom onset, baseline HHD overall megascore, and use of riluzole/edaravone. Missing data were handled using multiple imputation.
LS mean difference
0.02
Standard Error of the Mean
0.118
2-Sided
95
-0.207
0.255
Superiority
Units
Counts
Participants
OG00021
OG00139
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Not estimated due to insufficient number of participants with events.
OG001NA(NA to NA)Not estimated due to insufficient number of participants with events.
21
OG00139
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Not estimated due to insufficient number of participants with events.
OG001NA(NA to NA)Not estimated due to insufficient number of participants with events.