Study of ALXN1850 in Participants With Hypophosphatasia (... | NCT04980248 | Trialant
NCT04980248
Sponsor
Alexion Pharmaceuticals, Inc.
Status
Completed
Last Update Posted
Dec 27, 2024Actual
Enrollment
15Actual
Phase
Phase 1
Conditions
Hypophosphatasia
Interventions
ALXN1850
Countries
United States
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Derived Section
Miscellaneous Info Module
Version Holder
NCT04980248
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
ALXN1850-HPP-101
Secondary IDs
Not provided
Brief Title
Study of ALXN1850 in Participants With Hypophosphatasia (HPP)
Official Title
A Phase 1, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALXN1850 in Adults With Hypophosphatasia
Acronym
Not provided
Organization
Alexion Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Nov 2024
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
Sep 28, 2021Actual
Primary Completion Date
Aug 24, 2022Actual
Completion Date
Aug 24, 2022Actual
First Submitted Date
Jul 23, 2021
First Submission Date that Met QC Criteria
Jul 23, 2021
First Posted Date
Jul 28, 2021Actual
Results Waived
Not provided
Results First Submitted Date
Jul 26, 2024
Results First Submitted that Met QC Criteria
Nov 8, 2024
Results First Posted Date
Dec 27, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Nov 8, 2024
Last Update Posted Date
Dec 27, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Alexion Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Not provided
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
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP.
Detailed Description
Not provided
Conditions Module
Conditions
Hypophosphatasia
Keywords
HPP
enzyme replacement therapy
low alkaline phosphatase
tissue-nonspecific alkaline phosphatase
TNSALP
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
15Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
ALXN1850
Experimental
Three experimental cohorts will be administered 3 dosages (low, medium, high) of ALXN1850, respectively, via IV infusion and/or SC over multiple administration intervals.
Biological: ALXN1850
Interventions
Name
Type
Description
Arm Group Labels
Other Names
ALXN1850
Biological
ALXN1850 will be administered as an IV infusion and via the SC route.
ALXN1850
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Day 1 up to Day 85
Secondary Outcomes
Measure
Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3
Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Confirmed clinical diagnosis of HPP
Not anticipated to require further treatment with enzyme replacement therapy to treat participant's HPP after study completion
Willing and able to follow protocol-specified contraception requirements
Willing and able to give informed consent
Exclusion Criteria:
Primary or secondary hyperparathyroidism or hypoparathyroidism
Fracture within 12 weeks of screening
Current or relevant history of unstable physical or psychiatric illness
Significant allergies
Asfotase alfa use within 6 months and/or positive for asfotase alfa antidrug antibody/neutralizing antibodies
Dahir KM, Shannon A, Dunn D, Voegtli W, Dong Q, Hasan J, Pradhan R, Pelto R, Pan WJ. Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia. J Bone Miner Res. 2024 Sep 26;39(10):1412-1423. doi: 10.1093/jbmr/zjae128.
Participants received 15 milligrams (mg) of ALXN1850 as a single intravenous dose, followed by 15 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
FG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
FG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG0005 subjects
FG0015 subjects
FG0025 subjects
Received at Least 1 Dose of Study Drug
FG0005 subjects
FG0015 subjects
FG0025 subjects
COMPLETED
FG0005 subjects
FG0015 subjects
FG0025 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
Baseline Characteristics Module
Baseline Analysis Population Description
The Safety Set included all participants who received any amount of study drug. Participants were analyzed according to the study drug received.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1
Participants received 15 mg of ALXN1850 as a single intravenous dose, followed by 15 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
BG001
Cohort 2
Denominators
Units
Counts
Participants
BG000
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Outcome Measures Module
Outcome Measures
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
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
TEAEs were defined as any adverse events (AEs) that began or worsened on or after the first dose of treatment until the final follow-up visit. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. TESAEs were defined as any serious AEs that began or worsened on or after the first dose of treatment until the final follow-up visit. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
The Safety Set included all participants who received any amount of study drug. Participants were analyzed according to the study drug received.
Posted
Count of Participants
Participants
Day 1 up to Day 85
Adverse Events Module
Frequency Threshold
0
Time Frame
Baseline up to Day 85
Description
All-cause mortality is reported for all enrolled participants. Serious adverse events and other adverse events are reported in the Safety Set, which included all participants who received any amount of study drug. Participants were analyzed according to the study drug received.
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
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Browse Leaves
Not provided
Browse Branches
Not provided
Intervention Browse Module
No data available
No data is available for this block.
N/A
Intervention Model
Sequential Assignment
Intervention Model Description
Study participants will be enrolled into 3 cohorts in a sequential fashion.
Primary Purpose
Basic Science
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3
Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850
Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP at Week 1
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PPi at Week 1
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status
Baseline up to Day 85
Columbus
Ohio
43203
United States
Research Site
Nashville
Tennessee
37232
United States
Research Site
Austin
Texas
78744
United States
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
BG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
BG003
Total
Total of all reporting groups
5
BG0015
BG0025
BG00315
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00044.2± 12.44
BG00137.8± 12.52
BG00254.6± 9.07
BG00345.5± 12.80
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0003
BG0013
BG0025
BG00311
Male
BG0002
BG0012
BG0020
BG0034
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG0020
BG0030
Not Hispanic or Latino
BG0005
BG0015
BG0025
BG00315
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG0020
BG0030
Asian
BG0000
BG0010
BG0020
BG0030
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
Black or African American
BG0000
BG0010
BG0020
BG0030
White
BG0005
BG0015
BG0025
BG00315
More than one race
BG0000
BG0010
BG0020
BG0030
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0005
OG0015
OG0025
Title
Denominators
Categories
TEAEs
Title
Measurements
OG0003
OG0015
OG0024
TESAEs
Title
Measurements
OG0000
OG0010
OG0021
Secondary
Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3
The Pharmacokinetic (PK) Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, number analyzed signifies those participants who were evaluable for prespecified categories only.
Posted
Geometric Mean
Geometric Coefficient of Variation
micrograms/milliliter
Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0005
OG0015
OG0025
Title
Denominators
Categories
IV Dose
ParticipantsOG0005
ParticipantsOG0015
ParticipantsOG0025
Title
Measurements
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850
The PK Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*micrograms/milliliter
Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0004
OG0015
OG0024
Title
Denominators
Categories
Title
Measurements
OG000407± 38.3
OG0011010± 26.0
OG0022450± 33.6
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3
The PK Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, overall number of participants analyzed signfies those participants who were evaluable for this endpoint only and number analyzed signifies those participants who were evaluable for prespecified categories only.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*micrograms/milliliter
Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0005
OG0015
OG0024
Title
Denominators
Categories
SC Dose 1
ParticipantsOG0005
ParticipantsOG0015
ParticipantsOG0024
Title
Measurements
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850
The PK Set included all treated participants for whom the PK profile of ALXN1850 was adequately characterized. PK analyses was based upon the study drug received. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. As pre-specified, data are presented pooled for all participants who received study drug.
Posted
Geometric Least Squares Mean
90% Confidence Interval
Ratio
Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
ID
Title
Description
OG000
All Participants
Participants received 15, 45 or 90 mg of ALXN1850 as a single intravenous dose, followed by 15, 45 or 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG00015
Title
Denominators
Categories
15 mg
Title
Measurements
OG0000.286(0.105 to 0.782)
45 mg
Title
Measurements
OG0000.367(0.180 to 0.784)
90 mg
Secondary
Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1
The Pharmacodynamic (PD) Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
Posted
Mean
Standard Deviation
nanogram/milliliter
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0004
OG0014
OG0024
Title
Denominators
Categories
1 Week post Day 1 IV Dose
ParticipantsOG0001
ParticipantsOG0011
ParticipantsOG0021
Title
Measurements
Secondary
Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1
The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Number analyzed signifies those participants who were evaluable for the prespecified timepoints only.
Posted
Mean
Standard Deviation
micromoles (uM)
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0004
OG0012
OG0021
Title
Denominators
Categories
1 Week post Day 1 IV Dose
ParticipantsOG0001
ParticipantsOG0011
ParticipantsOG0020
Title
Measurements
Secondary
Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1
The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
Posted
Mean
Standard Deviation
Ratio
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0004
OG0014
OG0024
Title
Denominators
Categories
1 Week post Day 1 IV Dose
ParticipantsOG0001
ParticipantsOG0011
ParticipantsOG0021
Title
Measurements
Secondary
Percent Change From Baseline in Plasma Concentration of PLP at Week 1
The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
Posted
Mean
Standard Deviation
percent change
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0004
OG0014
OG0024
Title
Denominators
Categories
1 Week post Day 1 IV Dose
ParticipantsOG0001
ParticipantsOG0011
ParticipantsOG0021
Title
Measurements
Secondary
Percent Change From Baseline in Plasma Concentration of PPi at Week 1
The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Number analyzed signifies those participants who were evaluable for prespecified timepoints only.
Posted
Mean
Standard Deviation
percent change
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0004
OG0012
OG0021
Title
Denominators
Categories
1 Week post Day 1 IV Dose
ParticipantsOG0001
ParticipantsOG0011
ParticipantsOG0020
Title
Measurements
Secondary
Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1
The PD Set included all treated participants for whom the PD profile of ALXN1850 was adequately characterized. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure only. Here, number analyzed signifies those participants who were evaluable for prespecified timepoints only.
Posted
Mean
Standard Deviation
percent change
Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0004
OG0014
OG0024
Title
Denominators
Categories
1 Week post Day 1 IV Dose
ParticipantsOG0001
ParticipantsOG0011
ParticipantsOG0021
Title
Measurements
Secondary
Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status
The Immunogenicity Analysis Set included all treated participants who received any study drug and who after the first dose had at least one reportable result in the ADA assay.
Posted
Count of Participants
Participants
Baseline up to Day 85
ID
Title
Description
OG000
Cohort 1
Participants received 15 mg as a single intravenous dose, followed by 15 mg subcutaneous at 1-week interval for 3 doses.
OG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
OG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
Units
Counts
Participants
OG0005
OG0015
OG0025
Title
Denominators
Categories
ADA Positive
Title
Measurements
OG0002
OG0010
OG0022
NAb Positive
0
5
0
5
3
5
EG001
Cohort 2
Participants received 45 mg of ALXN1850 as a single intravenous dose, followed by 45 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
0
5
0
5
5
5
EG002
Cohort 3
Participants received 90 mg of ALXN1850 as a single intravenous dose, followed by 90 mg of ALXN1850 as a subcutaneous injection at 1-week interval for 3 doses.
0
5
1
5
4
5
EG0000 affected5 at risk
EG0010 affected5 at risk
EG0021 affected5 at risk
EG0001 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Injection site bruising
General disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Injection site erythema
General disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0021 affected5 at risk
Injection site haemorrhage
General disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Injection site pruritus
General disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Injection site reaction
General disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected5 at risk
EG0020 affected5 at risk
Vessel puncture site bruise
General disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected5 at risk
EG0020 affected5 at risk
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Muscle tightness
Musculoskeletal and connective tissue disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected5 at risk
EG0021 affected5 at risk
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Headache
Musculoskeletal and connective tissue disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0012 affected5 at risk
EG0020 affected5 at risk
Dizziness
Musculoskeletal and connective tissue disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected5 at risk
EG0020 affected5 at risk
Coronavirus infection
Infections and infestations
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0022 affected5 at risk
Urinary tract infection
Infections and infestations
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Vulvovaginal mycotic infection
Infections and infestations
MedDRA version 25.0
Systematic Assessment
This AE is gender specific. So, the number of participants at risk is the female population only.
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected5 at risk
Hyperphosphataemia
Metabolism and nutrition disorders
MedDRA version 25.0
Systematic Assessment
EG0002 affected5 at risk
EG0010 affected5 at risk
EG0020 affected5 at risk
Decreased appetite
Metabolism and nutrition disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected5 at risk
EG0020 affected5 at risk
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Anaemia
Blood and lymphatic system disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Abdominal pain
Blood and lymphatic system disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Nausea
Blood and lymphatic system disorders
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected5 at risk
EG0020 affected5 at risk
Blood phosphorus increased
Investigations
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0010 affected5 at risk
EG0021 affected5 at risk
Gamma-glutamyltransferase increased
Investigations
MedDRA version 25.0
Systematic Assessment
EG0001 affected5 at risk
EG0010 affected5 at risk
EG0020 affected5 at risk
Haematuria
Renal and urinary disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0012 affected5 at risk
EG0020 affected5 at risk
Hyperphosphaturia
Renal and urinary disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Dry eye
Cardiac disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Breast discomfort
Reproductive system and breast disorders
MedDRA version 25.0
Systematic Assessment
This AE is gender specific. So. the number of participants at risk is the female population only.
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected5 at risk
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Hypertension
Vascular disorders
MedDRA version 25.0
Systematic Assessment
EG0000 affected5 at risk
EG0011 affected5 at risk
EG0020 affected5 at risk
Not provided
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Not provided
D008659
Metabolic Diseases
D009750
Nutritional and Metabolic Diseases
OG0005.31± 29.2
OG00113.5± 23.3
OG00232.4± 31.1
SC Dose 1
ParticipantsOG0005
ParticipantsOG0015
ParticipantsOG0025
Title
Measurements
OG0000.871± 43.8
OG0012.89± 59.4
OG0028.60± 43.5
SC Dose 2
ParticipantsOG0005
ParticipantsOG0014
ParticipantsOG0025
Title
Measurements
OG0000.815± 52.3
OG0012.38± 88.8
OG0026.33± 55.5
SC Dose 3
ParticipantsOG0005
ParticipantsOG0014
ParticipantsOG0024
Title
Measurements
OG0000.844± 75.2
OG0012.41± 97.4
OG0025.44± 145
OG000115± 42.2
OG001383± 58.1
OG0021110± 49.6
SC Dose 2
ParticipantsOG0005
ParticipantsOG0014
ParticipantsOG0024
Title
Measurements
OG000111± 58.5
OG001350± 83.3
OG002872± 65.5
SC Dose 3
ParticipantsOG0005
ParticipantsOG0014
ParticipantsOG0024
Title
Measurements
OG000115± 73.9
OG001367± 95.6
OG002881± 104
Title
Measurements
OG0000.368(0.0908 to 1.49)
OG000-18.300± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG001-7.600± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG002-49.460± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
1 Week post Day 29 SC Dose 3
ParticipantsOG0004
ParticipantsOG0014
ParticipantsOG0024
Title
Measurements
OG000-97.950± 164.0193
OG001-38.573± 26.4932
OG002-28.055± 17.3237
OG000-1.620± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG001-1.930± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
1 Week post Day 29 SC Dose 3
ParticipantsOG0004
ParticipantsOG0012
ParticipantsOG0021
Title
Measurements
OG000-0.813± 0.5970
OG001-1.505± 0.1202
OG002-2.040± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG000-8.570± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG001-16.070± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG002-15.260± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
1 Week post Day 29 SC Dose 3
ParticipantsOG0004
ParticipantsOG0014
ParticipantsOG0024
Title
Measurements
OG000-7.620± 5.3878
OG001-15.285± 6.2807
OG002-8.368± 6.3951
OG000-47.906± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG001-17.512± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG002-86.318± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
1 Week post Day 29 SC Dose 3
ParticipantsOG0004
ParticipantsOG0014
ParticipantsOG0024
Title
Measurements
OG000-33.895± 42.5254
OG001-69.049± 16.5385
OG002-70.515± 23.0447
OG000-53.821± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG001-70.956± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
1 Week post Day 29 SC Dose 3
ParticipantsOG0004
ParticipantsOG0012
ParticipantsOG0021
Title
Measurements
OG000-32.740± 23.0615
OG001-55.328± 1.7622
OG002-71.329± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG000-65.270± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG001-92.944± NAStandard deviation could not be calculated as there was only 1 evaluable participant.
OG002-91.323± NAStandard deviation could not be calculated as there was only 1 evaluable participant.