Safety, Tolerability, Pharmacokinetics, and Pharmacodynam... | NCT03186989 | Trialant
NCT03186989
Sponsor
Ionis Pharmaceuticals, Inc.
Status
Completed
Last Update Posted
Apr 8, 2025Actual
Enrollment
46Actual
Phase
Phase 1
Conditions
Mild Alzheimer's Disease
Interventions
IONIS MAPTRx
Placebo
Countries
Canada
Finland
Germany
Netherlands
Sweden
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03186989
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
ISIS 814907-CS1
Secondary IDs
ID
Type
Description
Link
NL60032.000.16
Other Identifier
CCMO
2016-002713-22
EudraCT Number
Brief Title
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease
Official Title
A Randomized, Double-Blind, Placebo-Controlled Study, Followed by an Open-Label Extension, to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 814907 in Patients With Mild Alzheimer's Disease
Acronym
Not provided
Organization
Ionis Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Mar 2025
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
Oct 12, 2017Actual
Primary Completion Date
May 12, 2022Actual
Completion Date
May 12, 2022Actual
First Submitted Date
Jun 6, 2017
First Submission Date that Met QC Criteria
Jun 13, 2017
First Posted Date
Jun 14, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Oct 31, 2023
Results First Submitted that Met QC Criteria
Mar 20, 2025
Results First Posted Date
Apr 8, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Feb 16, 2023
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Apr 8, 2025Actual
Last Update Submitted Date
Mar 20, 2025
Last Update Posted Date
Apr 8, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Ionis Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
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
Yes
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-MAPTRx in patients with Mild Alzheimer's Disease.
Detailed Description
This was a randomized, double-blind, placebo-controlled study in 46 participants, followed by an Open-Label Extension. This study consisted of two parts:
Part 1: a randomized, double-blind, placebo-controlled multiple ascending dose period in participants with Mild Alzheimer's Disease, followed by Part 2: the open-label, long-term extension period.
Conditions Module
Conditions
Mild Alzheimer's Disease
Keywords
Mild Alzheimer's Disease
ISIS 814907
Memory Loss
Alzheimers
MAPT
Tau
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 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
46Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1: Cohort A: ISIS 814907 10 mg
Experimental
Participants received 10 milligrams (mg) ISIS 814907 diluted in 20 milliliters (mL) artificial cerebrospinal fluid (CSF), intrathecally, every four weeks (Q4W) on Days 1, 29, 57, and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Part 1: Cohort B: ISIS 814907 30 mg
Experimental
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Part 1: Cohort C: ISIS 814907 60 mg
Experimental
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Part 1: Cohort D: ISIS 814907 115 mg
Experimental
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, every 12 weeks (Q12W) on Days 1 and 85 in Part 1 of the study.
Drug: IONIS MAPTRx
Part 1: Pooled Placebo
Placebo Comparator
Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
IONIS MAPTRx
Drug
IONIS MAPTRx injections.
Part 1: Cohort A: ISIS 814907 10 mg
Part 1: Cohort B: ISIS 814907 30 mg
Part 1: Cohort C: ISIS 814907 60 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
From first dose of study drug up to Week 37 in Part 1
Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
From first dose of study drug up to Week 64 in Part 2
Secondary Outcomes
Measure
Description
Time Frame
CSF Trough Concentration of ISIS 814907
Pre dose on Day 85 in Part 1 and Day 337 in Part 2
Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-intrathecal (IT) bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria for Part 1:
Males or females aged 50-74 years, inclusive, at the time of informed consent
Diagnosed with mild Alzheimers disease, including CSF biomarkers consistent with this diagnosis
Body Mass Index BMI ≥ 18 and ≤ 35 kg/m2 and total body weight > 50 kg (110 lbs)
Able and willing to meet all study requirements, including toleration for MRI scans, blood draws and lumbar punctures, travel to Study Center and participation in all procedures and measurements at study visits
Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the patient to select trial visits and to be available to the Study Center by phone if needed
Reside within 4 hours travel of the Study Center
Exclusion Criteria for Part 1:
Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer
Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study
Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures
Inclusion Criteria for Part 2:
Must have completed the Treatment Evaluation and Post-Treatment Periods in Part 1
Exclusion Criteria for Part 2 (only applicable to participants in Cohorts A and B, as participants from Cohorts C and D will seamlessly transition to Part 2):
Treatment with another Study Drug, biological agent, or device within one-month of Screening or 5 half-lives of investigational agent, whichever is longer
Clinically significant medical condition which would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study
Use of a disallowed CNS-active or antipsychotic medication within 4 weeks prior to Screening punctures
Shulman M, Wu S, Ziogas N, Edwards A, Collins J, Lin L, Tien I, Curiale G, Li Y, Mummery C, Lane R, Junge C, Beaver J, Tian Y, Landen J, Bullain S, Gallagher D. Exploratory analyses of clinical outcomes from the BIIB080 phase 1b study in mild Alzheimer's disease. Nat Aging. 2026 Feb;6(2):445-453. doi: 10.1038/s43587-025-01031-9. Epub 2026 Feb 11.
A total of 102 participants were screened and 46 participants with mild Alzheimer's disease were enrolled and randomized to receive ISIS 814907 or placebo in Part 1 (multiple ascending dose [MAD]). This study consists of two parts i.e., Part 1: MAD and Part 2: long-term extension (LTE). Out of 46 participants enrolled in Part 1, 33 participants who met the pre-specified eligibility criteria transitioned into Part 2.
Recruitment Details
The study was conducted at 12 investigative sites in the Germany, United Kingdom, the Netherlands, Sweden, Canada, and Finland from 23 August 2017 to 12 May 2022.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 milligrams (mg) ISIS 814907 diluted in 20 millilitres (mL) artificial cerebrospinal fluid (CSF), intrathecally, every four weeks (Q4W) on Days 1, 29, 57, and 85 in Part 1 of the study.
FG001
Part 1: Cohort B: ISIS 814907 30 mg
Periods
Title
Milestones
Reasons Not Completed
Part 1: MAD (Day 1 up to Week 36)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
Apr 27, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Other
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Other: Placebo
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg
Experimental
Participants from MAD Cohorts A, B, C that were placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Part 2: Late Start Cohort D + ISIS 814907 115 mg
Experimental
Participants from MAD Cohort D that were placebo-treated, received 115 mg ISIS 814907 diluted up in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Part 2: Early Start Cohort A + ISIS 814907 60 mg
Experimental
Participants from MAD Cohort A that were ISIS 814907 10 mg -treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Part 2: Early Start Cohort B + ISIS 814907 60 mg
Experimental
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Part 2: Early Start Cohort C + ISIS 814907 60 mg
Experimental
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Part 2: Early Start Cohort D + ISIS 814907 115 mg
Experimental
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Drug: IONIS MAPTRx
Part 1: Cohort D: ISIS 814907 115 mg
Part 2: Early Start Cohort A + ISIS 814907 60 mg
Part 2: Early Start Cohort B + ISIS 814907 60 mg
Part 2: Early Start Cohort C + ISIS 814907 60 mg
Part 2: Early Start Cohort D + ISIS 814907 115 mg
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg
Part 2: Late Start Cohort D + ISIS 814907 115 mg
ISIS 814907
Placebo
Other
Artificial CSF injections.
Part 1: Pooled Placebo
Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
Turku
Finland
St Josef Hospital
Bochum
Germany
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Bonn
53127
Germany
MVZ Mittweida Gbr
Mittweida
Germany
Universittsklinikum Ulm
Ulm
Germany
VU University Medical Center
Amsterdam
1081 HV
Netherlands
QPS Netherlands BV
Groningen
9713 AG
Netherlands
Minnesmottagningen
Mölndal
Sweden
Karolinska University Hospital Huddinge
Stockholm
Sweden
Royal Liverpool University Hospital
Liverpool
United Kingdom
University College London Hospitals NHS Foundation Trust
London
United Kingdom
Sheffield Institute for Translational Neuroscience (SITraN)
Sheffield
United Kingdom
Derived
Lane RM, Darreh-Shori T, Junge C, Li D, Yang Q, Edwards AL, Graham DL, Moore K, Mummery CJ. Onset of Alzheimer disease in apolipoprotein varepsilon4 carriers is earlier in butyrylcholinesterase K variant carriers. BMC Neurol. 2024 Apr 9;24(1):116. doi: 10.1186/s12883-024-03611-5.
Edwards AL, Collins JA, Junge C, Kordasiewicz H, Mignon L, Wu S, Li Y, Lin L, DuBois J, Hutchison RM, Ziogas N, Shulman M, Martarello L, Graham D, Lane R, Budd Haeberlein S, Beaver J. Exploratory Tau Biomarker Results From a Multiple Ascending-Dose Study of BIIB080 in Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. 2023 Dec 1;80(12):1344-1352. doi: 10.1001/jamaneurol.2023.3861.
Mummery CJ, Borjesson-Hanson A, Blackburn DJ, Vijverberg EGB, De Deyn PP, Ducharme S, Jonsson M, Schneider A, Rinne JO, Ludolph AC, Bodenschatz R, Kordasiewicz H, Swayze EE, Fitzsimmons B, Mignon L, Moore KM, Yun C, Baumann T, Li D, Norris DA, Crean R, Graham DL, Huang E, Ratti E, Bennett CF, Junge C, Lane RM. Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial. Nat Med. 2023 Jun;29(6):1437-1447. doi: 10.1038/s41591-023-02326-3. Epub 2023 Apr 24.
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
FG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
FG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, every 12 weeks (Q12W) on Days 1 and 85 in Part 1 of the study.
FG004
Part 1: Pooled Placebo
Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study.
FG005
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg
Participants from MAD Cohorts A, B, C that were placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
FG006
Part 2: Late Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were placebo-treated, received 115 mg ISIS 814907 diluted up in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
FG007
Part 2: Early Start Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg -treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
FG008
Part 2: Early Start Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
FG009
Part 2: Early Start Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
FG010
Part 2: Early Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
FG0006 subjects
FG0016 subjects
FG0029 subjects
FG00313 subjects
FG00412 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
COMPLETED
FG0006 subjects
FG0016 subjects
FG0028 subjects
FG00312 subjects
FG00411 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
Type
Comment
Reasons
Voluntary Withdrawal
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
Part 2: LTE (Week 37 to Week 101)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0054 subjects
FG0064 subjects
FG0073 subjects
FG0085 subjects
FG0097 subjects
FG01010 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
Voluntary Withdrawal
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
BG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
BG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
BG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1 and 85 in Part 1 of the study.
BG004
Part 1: Pooled Placebo
Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0006
BG0016
BG0029
BG00313
BG00412
BG00546
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
Title
Measurements
BG00063.5± 5.2
BG00165.0± 6.1
BG00265.6± 6.8
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0014
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
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
Part 1: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
Safety population included all participants who were randomised and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
From first dose of study drug up to Week 37 in Part 1
ID
Title
Description
OG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1 and 85 in Part 1 of the study.
OG004
Part 1: Pooled Placebo
Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study.
Units
Counts
Participants
OG0006
OG0016
OG0029
OG003
Title
Denominators
Categories
Mild
Title
Measurements
OG0003
OG0010
OG0025
OG003
Primary
Part 2: Number of Participants With Adverse Events That Are Related to Treatment With ISIS 814907
An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. A TEAE was defined as any AE that starts or worsens on or after the date of first dose of study treatment. TEAEs were categorised as mild, moderate, and severe to aid in severity assessment.
Safety population included all participants who were randomised and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
From first dose of study drug up to Week 64 in Part 2
ID
Title
Description
OG000
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg
Participants from MAD Cohorts A, B, C that were placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG001
Part 2: Late Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were placebo-treated, received 115 mg ISIS 814907 diluted up in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG002
Secondary
CSF Trough Concentration of ISIS 814907
PK population consisted of all participants who were randomized, received at least 1 dose of ISIS 814907, and had sufficient sampling (at least 1 evaluable post-Baseline PK sample) to permit PK evaluation. Overall number of participants analyzed is number of participants who received active treatment (ISIS 814907) in Part 1 or received active treatment in Part 2. As pre-specified in SAP, in case of very few participants in any active treatment groups, the analysis groups may have been pooled.
Posted
Mean
Standard Deviation
nanogram per millilitre (ng/mL)
Pre dose on Day 85 in Part 1 and Day 337 in Part 2
ID
Title
Description
OG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Secondary
Maximum Observed Drug Concentration (Cmax) of ISIS 814907 in Plasma
PK population consisted of all participants who were randomized, received at least 1 dose of ISIS 814907, and had sufficient sampling (at least 1 evaluable post-Baseline PK sample) to permit PK evaluation. Overall number of participants analyzed is number of participants who received active treatment (ISIS 814907) in Part 1 or received active treatment in Part 2. As pre-specified in SAP, in case of very few participants in any active treatment groups, the analysis groups may have been pooled.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-intrathecal (IT) bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
ID
Title
Description
OG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Secondary
Time Taken to Reach Maximal Concentration (Tmax) of ISIS 814907 in Plasma
PK population consisted of all participants who were randomized, received at least 1 dose of ISIS 814907, and had sufficient sampling (at least 1 evaluable post-Baseline PK sample) to permit PK evaluation. Overall number of participants analyzed is number of participants who received active treatment (ISIS 814907) in Part 1 or received active treatment in Part 2. As pre-specified in SAP, in case of very few participants in any active treatment groups, the analysis groups may have been pooled.
Posted
Median
Full Range
hours
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
ID
Title
Description
OG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Secondary
Terminal Elimination Half-life (t1/2λz) of ISIS 814907 in Plasma
PK population consisted of all participants who were randomized, received at least 1 dose of ISIS 814907, and had sufficient sampling (at least 1 evaluable post-Baseline PK sample) to permit PK evaluation. Overall number of participants analyzed is number of participants who received active treatment (ISIS 814907) in Part 1 or received active treatment in Part 2. As pre-specified in SAP, in case of very few participants in any active treatment groups, the analysis groups may have been pooled.
Posted
Geometric Mean
Geometric Coefficient of Variation
days
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
ID
Title
Description
OG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
Secondary
Areas Under the Plasma Concentration-time Curve From Zero Time (Predose) to 24 Hours After the IT Administration (AUC0-24h) of ISIS 814907
PK population consisted of all participants who were randomized, received at least 1 dose of ISIS 814907, and had sufficient sampling (at least 1 evaluable post-Baseline PK sample) to permit PK evaluation. Overall number of participants analyzed is number of participants who received active treatment (ISIS 814907) in Part 1 or received active treatment in Part 2. As pre-specified in SAP, in case of very few participants in any active treatment groups, the analysis groups may have been pooled.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hours per millilitre (ng*h/mL)
Pre-dose, 0.5, 1, 2, 3, 4, and 5 hours post-IT bolus injection on Day 85 in Part 1 and on Day 337 in Part 2
ID
Title
Description
OG000
Part 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG002
Part 1: Cohort C: ISIS 814907 60 mg
Time Frame
From first dose of study drug up to Week 37 in Part 1 and up to Week 64 in Part 2
Description
Safety population included all participants who were randomized and received at least 1 dose of study drug.
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 1: Cohort A: ISIS 814907 10 mg
Participants received 10 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
0
6
0
6
6
6
EG001
Part 1: Cohort B: ISIS 814907 30 mg
Participants received 30 mg ISIS 814907 diluted in 20 mL in artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
0
6
0
6
5
6
EG002
Part 1: Cohort C: ISIS 814907 60 mg
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
0
9
0
9
9
9
EG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, ev(Q12W) on Days 1 and 85 in Part 1 of the study.
0
13
0
13
12
13
EG004
Part 1: Pooled Placebo
Participants received 20 mL artificial CSF, intrathecally, as placebo on Days 1, 29, 57, and 85 for the 4-dose regimens, or on Days 1 and 85 for the 2-dose regimens in Part 1 of the study.
0
12
2
12
9
12
EG005
Part 2: Late Start Cohort A + Cohort B + Cohort C + ISIS 814907 60 mg
Participants from MAD Cohorts A, B, C that were placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
0
4
1
4
4
4
EG006
Part 2: Late Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were placebo-treated, received 115 mg ISIS 814907 diluted up in 20 mL artificial CSF, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
0
4
0
4
3
4
EG007
Part 2: Early Start Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg -treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
0
3
1
3
3
3
EG008
Part 2: Early Start Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
0
5
1
5
4
5
EG009
Part 2: Early Start Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
0
7
0
7
7
7
EG010
Part 2: Early Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
0
1
1
10
10
10
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Cerebrovascular accident
Nervous system disorders
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG0030 affected13 at risk
EG0041 affected12 at risk
EG0050 affected4 at risk
EG0060 affected4 at risk
EG0070 affected3 at risk
EG0080 affected5 at risk
EG0090 affected7 at risk
EG0100 affected10 at risk
Balance disorder
Nervous system disorders
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG003
Parkinsonism
Nervous system disorders
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG003
Aggression
Psychiatric disorders
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG003
Paranoia
Psychiatric disorders
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA20.0
Systematic Assessment
EG0000 affected6 at risk
EG0010 affected6 at risk
EG0020 affected9 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Lipoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Participants from MAD Cohort A that were ISIS 814907 10 mg -treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG003
Part 2: Early Start Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG004
Part 2: Early Start Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG005
Part 2: Early Start Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Units
Counts
Participants
OG0004
OG0014
OG0023
OG0035
OG0047
OG00510
Title
Denominators
Categories
Mild
Title
Measurements
OG0001
OG0010
OG0021
OG0031
OG0040
OG0052
Moderate
Title
Measurements
OG0000
OG0012
OG0021
OG003
Severe
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1 and 85 in Part 1 of the study.
OG004
Part 2: Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG005
Part 2: Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG006
Part 2: Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG007
Part 2: Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated or placebo-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Units
Counts
Participants
OG0006
OG0016
OG0029
OG00312
OG0042
OG0055
OG0069
OG00711
Title
Denominators
Categories
Title
Measurements
OG0005.56± 2.12
OG0019.77± 3.46
OG0029.79± 3.42
OG0033.26± 1.24
OG0045.96± NAThe values were non-quantifiable \[NQ\] (50% of values were imputed i.e., NQ assigned zero concentration for one participant) which affected the calculation. Since only one participant had evaluable data SD was not estimable.
OG0058.22± 2.03
OG0066.61± 2.89
OG0077.82± 2.52
OG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1 and 85 in Part 1 of the study.
OG004
Part 2: Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG005
Part 2: Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG006
Part 2: Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG007
Part 2: Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated or placebo-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Units
Counts
Participants
OG0006
OG0016
OG0029
OG00313
OG0042
OG0055
OG0069
OG00712
Title
Denominators
Categories
Title
Measurements
OG00065.4± 203
OG001285± 50.5
OG002542± 148
OG003830± 879
OG004840± NAGeometric coefficient of variation was not estimable due to insufficient number of participants with events.
OG005323± 56.6
OG006524± 90.2
OG0071011± 130
OG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1 and 85 in Part 1 of the study.
OG004
Part 2: Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG005
Part 2: Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG006
Part 2: Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study
OG007
Part 2: Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated or placebo-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Units
Counts
Participants
OG0006
OG0016
OG0029
OG00313
OG0042
OG0055
OG0069
OG00712
Title
Denominators
Categories
Title
Measurements
OG0003.13(1.02 to 24.7)
OG0014.00(3.02 to 5.00)
OG0024.02(2.00 to 24.2)
OG0033.38(1.02 to 338)
OG0042.05(1.02 to 3.08)
OG0054.02(3.02 to 5.07)
OG0064.15(2.02 to 24.3)
OG0074.03(0.500 to 23.5)
OG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1 and 85 in Part 1 of the study.
OG004
Part 2: Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG005
Part 2: Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG006
Part 2: Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG007
Part 2: Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated or placebo-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Units
Counts
Participants
OG0006
OG0016
OG0029
OG00313
OG0042
OG0055
OG0069
OG00712
Title
Denominators
Categories
Title
Measurements
OG00019.4± 62.7
OG00138.0± 23.1
OG00234.8± 22.6
OG00342.5± 16.1
OG00410.7± NAGeometric coefficient of variation was not estimable due to insufficient number of participants with events.
OG00510.3± 8.99
OG00610.6± 16.3
OG00713.8± 54.0
Participants received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q4W on Days 1, 29, 57, and 85 in Part 1 of the study.
OG003
Part 1: Cohort D: ISIS 814907 115 mg
Participants received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1 and 85 in Part 1 of the study.
OG004
Part 2: Cohort A + ISIS 814907 60 mg
Participants from MAD Cohort A that were ISIS 814907 10 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG005
Part 2: Cohort B + ISIS 814907 60 mg
Participants from MAD Cohort B that were ISIS 814907 30 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG006
Part 2: Cohort C + ISIS 814907 60 mg
Participants from MAD Cohort C that were ISIS 814907 60 mg-treated or placebo-treated, received 60 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
OG007
Part 2: Cohort D + ISIS 814907 115 mg
Participants from MAD Cohort D that were ISIS 814907 115 mg-treated or placebo-treated, received 115 mg ISIS 814907 diluted in 20 mL artificial CSF, intrathecally, Q12W on Days 1, 85, 169, 253, and 337 in Part 2 of the study.
Units
Counts
Participants
OG0006
OG0016
OG0029
OG00313
OG0042
OG0055
OG0069
OG00712
Title
Denominators
Categories
Title
Measurements
OG000679± 119
OG0013638± 36.0
OG0026143± 92.4
OG0037120± 3066
OG00410523± NAGeometric coefficient of variation was not estimable due to insufficient number of participants with events.