A Study of Alirocumab in Participants With Autosomal Domi... | NCT01604824 | Trialant
NCT01604824
Sponsor
Regeneron Pharmaceuticals
Status
Completed
Last Update Posted
Jun 17, 2020Actual
Enrollment
23Actual
Phase
Phase 2
Conditions
Hypercholesterolemia
Interventions
Alirocumab
Placebo
Countries
United States
France
Protocol Section
Identification Module
NCT ID
NCT01604824
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
R727-CL-1018
Secondary IDs
Not provided
Brief Title
A Study of Alirocumab in Participants With Autosomal Dominant Hypercholesterolemia (ADH) and Gain-of-Function Mutations (GOFm) of the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) Gene or Loss-of-Function Mutations (LOFm) of the Apolipoprotein (Apo) B Gene
Official Title
A Phase 2 Pilot Study With a Randomized Double-Blind Treatment Phase to Evaluate the Pharmacodynamics and Safety of Alirocumab in Patients With Autosomal Dominant Hypercholesterolemia and Gain-of-Function Mutations in 1 or Both Alleles of the PCSK9 Gene or Loss-of-Function Mutations in 1 or More Alleles of the Loss-of-Function Mutations B Gene
Acronym
Not provided
Organization
Regeneron PharmaceuticalsINDUSTRY
Status Module
Record Verification Date
Jun 2020
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
Feb 22, 2012Actual
Primary Completion Date
Jun 2, 2014Actual
Completion Date
Jul 28, 2017Actual
First Submitted Date
May 22, 2012
First Submission Date that Met QC Criteria
May 22, 2012
First Posted Date
May 24, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 20, 2015
Results First Submitted that Met QC Criteria
Jun 4, 2020
Results First Posted Date
Jun 17, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 24, 2015
Certification/Extension First Submitted that Passed QC Review
Jan 24, 2015
Certification/Extension First Posted Date
Jan 30, 2015Estimated
Last Update Submitted Date
Jun 4, 2020
Last Update Posted Date
Jun 17, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Regeneron PharmaceuticalsINDUSTRY
Collaborators
Name
Class
Sanofi
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
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
The primary objective of the study is to assess the pharmacodynamic (PD) effect of alirocumab on serum low density lipoprotein cholesterol (LDL-C) during 14 weeks of subcutaneous (SC) administered alirocumab in patients with autosomal dominant hypercholesterolemia (ADH) and gain-of-function mutation (GOFm) in 1 or both alleles of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or with loss-of-function mutation (LOFm) in 1 or more alleles of the apolipoprotein (ApoB) gene.
Detailed Description
Not provided
Conditions Module
Conditions
Hypercholesterolemia
Keywords
Not provided
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 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
23Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
GOFm PCSK9 (Cohort 1): Alirocumab From Day 1
Experimental
Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group A). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Drug: Alirocumab
Drug: Placebo
GOFm PCSK9 (Cohort 1): Alirocumab From Day 15
Experimental
Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 ([matching placebo at Week 0 (Day 1), 10 and 14]) during the double-blind period (Group B). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Drug: Alirocumab
Drug: Placebo
GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1
Experimental
Participants with gain-of-function mutation (GOFm) in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in the apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group C). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Alirocumab
Drug
SC injection in the abdomen
GOFm PCSK9 (Cohort 1): Alirocumab From Day 1
GOFm PCSK9 (Cohort 1): Alirocumab From Day 15
GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percent Change in Measured Serum Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 15
By day 15, participants in groups A and C had received 1 subcutaneous (SC) dose of 150 mg alirocumab and participants in group B and D had received 1 SC dose of placebo. [Baseline adjusted least squares (LS) means and standard errors were obtained using analysis of covariance (ANCOVA) model specifying the treatment arm as the fixed effect and the baseline measured LDL-C value as a covariate.]
Baseline to Day 15
Secondary Outcomes
Measure
Description
Time Frame
Percent Change in Apolipoprotein (Apo) B100 From Baseline to Day 15
Baseline adjusted LS means and standard errors were obtained using the same ANCOVA model as for primary endpoint specifying the treatment arm as the fixed effect and the parameter value as a covariate.
Baseline to Day 15
Percent Change in Non High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 15
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Inclusion criteria include, but are not limited to the following:
Between the ages of 18 and 70 years, inclusive
A history of molecularly confirmed PCSK9 GOFm for cohort 1 and a history of molecularly confirmed PCSK9 GOFm or ApoB LOFm
Plasma LDL-Cholesterol levels ≥70 mg/dL at the screening visit on a lipid-lowering therapy (LLT) regimen stable for at least 28 days
Exclusion Criteria:
Exclusion criteria include, but are not limited to the following:
Serum triglycerides >350 mg/dL at the screening visit
Known to be positive for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
Pregnant or breast-feeding women.
Sexually active man or woman of childbearing potential who is unwilling to practice adequate contraception during the study
Hopkins PN, Krempf M, Bruckert E, Donahue S, Yang F, Zhang Y, DiCioccio AT. Pharmacokinetic and pharmacodynamic assessment of alirocumab in patients with familial hypercholesterolemia associated with proprotein convertase subtilisin/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations. J Clin Lipidol. 2019 Nov-Dec;13(6):970-978. doi: 10.1016/j.jacl.2019.10.007. Epub 2019 Oct 21.
Eligible participants entered a 2-wk, single-blind, placebo run-in period. Participants in cohort 1 were randomized in a 1:1 ratio (group A or B); Participants in cohort 2 were also randomized in a 1:1 ratio (group C or D).
Recruitment Details
This study was conducted at 4 sites, 3 in France & 1 in the United States. Twenty-eight participants were screened between Feb 2012 & Apr 2013. A total of 23 participants were enrolled: 13 in cohort 1 & 10 in cohort 2. Recruitment for cohort 2 occurred after the un-blinding of cohort 1 & analyses of the double-blind study data for cohort 1.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Periods
Title
Milestones
Reasons Not Completed
Double-blind (DB) Period
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
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantInvestigatorOutcomes Assessor
Drug: Alirocumab
Drug: Placebo
GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15
Experimental
Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 ([matching placebo at Week 0 (Day 1), 10 and 14]) during the double-blind period (Group D). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Drug: Alirocumab
Drug: Placebo
GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15
Praluent®
REGN727
SAR236553
Placebo
Drug
SC injection in the abdomen
GOFm PCSK9 (Cohort 1): Alirocumab From Day 1
GOFm PCSK9 (Cohort 1): Alirocumab From Day 15
GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1
GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15
Baseline to Day 15
Percent Change in Total Cholesterol (Total-C) From Baseline to Day 15
Baseline to Day 15
Percent Change in Apolipoprotein (Apo) B100/ ApoA-1 Ratio From Baseline to Day 15
Baseline to Day 15
Lille
Cedex
France
Nantes
Cedex
France
Paris
France
Derived
Hopkins PN, Defesche J, Fouchier SW, Bruckert E, Luc G, Cariou B, Sjouke B, Leren TP, Harada-Shiba M, Mabuchi H, Rabes JP, Carrie A, van Heyningen C, Carreau V, Farnier M, Teoh YP, Bourbon M, Kawashiri MA, Nohara A, Soran H, Marais AD, Tada H, Abifadel M, Boileau C, Chanu B, Katsuda S, Kishimoto I, Lambert G, Makino H, Miyamoto Y, Pichelin M, Yagi K, Yamagishi M, Zair Y, Mellis S, Yancopoulos GD, Stahl N, Mendoza J, Du Y, Hamon S, Krempf M, Swergold GD. Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody. Circ Cardiovasc Genet. 2015 Dec;8(6):823-31. doi: 10.1161/CIRCGENETICS.115.001129. Epub 2015 Sep 15.
FG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
FG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
FG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2: Group D)
Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
FG004
PCSK9 GOFm (Cohort 1: Group A and Group B)
Participants with a GOFm in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC, Q2W for an additional 3 years.
FG005
PCSK9 GOFm/ApoB LOFm (Cohort 2: Group C and Group D)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
FG0006 subjects
FG0017 subjects
FG0025 subjects
FG0035 subjects
FG0040 subjects
FG0050 subjects
Completed DB Period (Day 99)
FG0006 subjects
FG0017 subjects
FG0025 subjects
FG0035 subjects
FG0040 subjects
FG0050 subjects
Completed DB Follow-up (Day 155)
FG0006 subjects
FG0017 subjects
FG0025 subjects
FG0035 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG0006 subjects
FG0017 subjects
FG0025 subjects
FG0035 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Open-label Extension (OLE) Period
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00413 subjectsCompleted DB Period (Day 99)
FG00510 subjectsCompleted DB follow-up (Day 155)
Started Open-label Extension Period
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Completed Study
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Chose not to enter OLE Period
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
BG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
BG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
BG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2: Group D)
Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Baseline value is defined as the last available value prior to the first dose of double-blind period (alirocumab or placebo).
Mean
Standard Deviation
mg/dL
Title
Denominators
Categories
Title
Measurements
BG000124.3± 49.00
BG001
Apolipoprotein (Apo) B100
Baseline value is defined as the last available value prior to the first dose of double-blind period (alirocumab or placebo).
Mean
Standard Deviation
mg/dL
Title
Denominators
Categories
Title
Measurements
BG00089.2± 27.29
BG001101.0
Apolipoprotein (Apo) A1
Baseline value is defined as the last available value prior to the first dose of double-blind period (alirocumab or placebo).
Mean
Standard Deviation
mg/dL
Title
Denominators
Categories
Title
Measurements
BG000136.3± 29.75
BG001131.4
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
Percent Change in Measured Serum Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 15
By day 15, participants in groups A and C had received 1 subcutaneous (SC) dose of 150 mg alirocumab and participants in group B and D had received 1 SC dose of placebo. [Baseline adjusted least squares (LS) means and standard errors were obtained using analysis of covariance (ANCOVA) model specifying the treatment arm as the fixed effect and the baseline measured LDL-C value as a covariate.]
Posted
Least Squares Mean
Standard Error
percent change
Baseline to Day 15
ID
Title
Description
OG000
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2: Group D)
Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Units
Counts
Participants
OG0006
OG0017
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG000-62.48± 8.217(8.217 to )
OG001-8.77± 7.575(7.575 to )
OG002-48.21± 7.660(7.660 to )
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
= 0.0009
Threshold for significance ≤ 0.05
LS Mean Difference
-53.72
Standard Error of the Mean
11.486
2-Sided
95
-79.31
-28.12
Superiority
OG002
OG003
ANCOVA
Secondary
Percent Change in Apolipoprotein (Apo) B100 From Baseline to Day 15
Baseline adjusted LS means and standard errors were obtained using the same ANCOVA model as for primary endpoint specifying the treatment arm as the fixed effect and the parameter value as a covariate.
Posted
Least Squares Mean
Standard Error
percent change
Baseline to Day 15
ID
Title
Description
OG000
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Secondary
Percent Change in Non High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 15
Posted
Least Squares Mean
Standard Error
percent change
Baseline to Day 15
ID
Title
Description
OG000
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Secondary
Percent Change in Total Cholesterol (Total-C) From Baseline to Day 15
Posted
Least Squares Mean
Standard Error
percent change
Baseline to Day 15
ID
Title
Description
OG000
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Secondary
Percent Change in Apolipoprotein (Apo) B100/ ApoA-1 Ratio From Baseline to Day 15
Posted
Least Squares Mean
Standard Error
percent change
Baseline to Day 15
ID
Title
Description
OG000
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Time Frame
From the screening visit after the last alirocumab injection in the open-label period + 70 days through the end of study
Description
Observation periods for safety analyses: Pretreatment: screening to before 1st injection of alirocumab; Double-blind (DB) treatment-emergent (TE): after 1st through last in DB+70 days; Interim: after last in DB+70 days prior to 1st in open-label (OL). OL TE: after 1st through last in OL+70 days. Post: after last in OL+70 days through end of study.
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
PCSK9 GOFm: Alirocumab From Day 1 (Cohort 1: Group A)
Participants with a gain-of-function mutation (GOFm) in the PCSK9 gene (Cohort 1: Group A) received 150 mg alirocumab subcutaneously (SC) on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
0
6
1
6
6
6
EG001
PCSK9 GOFm: Alirocumab From Day 15 (Cohort 1: Group B)
Participants with a GOFm in PCSK9 gene (Cohort 1: Group B) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
0
7
0
7
6
7
EG002
PCSK9 GOFm/ApoB LOFm: Alirocumab From Day1 (Cohort 2: Group C)
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
0
5
0
5
5
5
EG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2:Group D)
Subjects with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Afterwards, subjects continued in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
0
5
0
5
4
5
EG004
OLE Period: PCSK9 GOFm (Cohort 1) Group A & Group B
Subjects with a GOFm in PCSK9 gene (Cohort 1): alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Weeks 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group A) or at Week 2 (Day 15), Weeks 4, 6, 8 and 12 (matching placebo at Week 0 [Day 1], Weeks 10 and 14) during the double-blind period (Group B). Afterwards, subjects continued in an OLE period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
0
11
3
11
10
11
EG005
OLE Period: PCSK9 GOFm/ ApoB LOFm (Cohort 2) Group C & Group D
Subjects with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2): alirocumab 150 mg SC injection at Week 0 (Day 1), Week 2 (Day 15), Weeks 4, 6 and 10 (matching placebo at Weeks 8, 12 and 14) during the double-blind period (Group C) or at Week 2 (Day 15), Weeks 4, 6, 8 and 12 (matching placebo at Week 0 [Day 1], 10 and 14) during the double-blind period (Group D). Afterwards, subjects continued in an OLE period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
0
10
0
10
9
10
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Chest pain
General disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG0030 events0 affected5 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected10 at risk
Angina unstable
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Salivary gland disorder
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Obesity
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Angina pectoris
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG0030 events0 affected5 at risk
EG0043 events2 affected11 at risk
EG0050 events0 affected10 at risk
Vertigo
Ear and labyrinth disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Dry eye
Eye disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Ocular hyperaemia
Eye disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Chest pain
General disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0002 events2 affected6 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Influenza
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Headache
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0013 events2 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Migraine
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0002 events1 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected5 at risk
EG003
Raynaud's phenomenon
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Ear pruritus
Ear and labyrinth disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Aphthous ulcer
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0003 events2 affected6 at risk
EG0011 events1 affected7 at risk
EG0024 events2 affected5 at risk
EG003
Angina unstable
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Prinzmetal angina
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Thyroid mass
Endocrine disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Dyspesia
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Functional gastrointestinal disorder
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Asthenia
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Inflammation
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Oedema peripheral
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Hepatic steatosis
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Cystitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Ear infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Fungal skin infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Infectious mononucleosis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Kidney infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Localised infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Otitis externa
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Sialoadenitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Tooth infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Cardiac procedure complication
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Joint dislocation
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Cardiac murmur
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Nitrite urine present
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
White blood cells urine positive
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Gout
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Vitamin B complex deficiency
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Tendonitis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Pituitary tumour benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Squamous cell carcinoma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Amnesia
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Diabetic neuropathy
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Nerve compression
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Dermatitis allergic
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Peau d'orange
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Syncope
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Benign prostatic hyperplasia
Reproductive system and breast disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Diabetic vascular disorder
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 at risk
EG003
Peripheral vascular disorder
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected5 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
The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Point of Contact
Title
Organization
Phone
Extension
Email
Clinical Trial Management
Regeneron Pharmaceuticals
844-734-6643
clinicaltrials@regeneron.com
ID
Term
D006937
Hypercholesterolemia
Ancestor Terms
ID
Term
D006949
Hyperlipidemias
D050171
Dyslipidemias
D052439
Lipid Metabolism Disorders
D008659
Metabolic Diseases
D009750
Nutritional and Metabolic Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C571059
alirocumab
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
11 subjects
Two subjects chose not to enter OLE period
FG00510 subjects
10 subjects
FG00510 subjects
10 subjects
FG00510 subjects
3 subjects
FG0050 subjects
0 subjects
FG0042 subjects
FG0050 subjects
Refused to come into office
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
42.0
± 10.84
BG00444.2± 11.15
0
BG0030
BG0040
Preterm newborn infants (gestational age < 37 wks)
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
Newborns (0-27 days)
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
Infants and toddlers (28 days-23 months)
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
Children (2-11 years)
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
Adolescents (12-17 years)
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
Adults (18-64 years)
Title
Measurements
BG0006
BG0017
BG0025
BG0035
BG00423
From 65-84 years
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
85 years and over
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
4
BG0032
BG00415
Male
BG0002
BG0012
BG0021
BG0033
BG0048
0
BG0030
BG0040
Not Hispanic or Latino
BG0006
BG0017
BG0025
BG0035
BG00423
5
BG0035
BG00421
Black or African American
BG0000
BG0010
BG0020
BG0030
BG0040
Asian
BG0000
BG0010
BG0020
BG0030
BG0040
American Indian or Alaska Native
BG0000
BG0010
BG0020
BG0030
BG0040
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
BG0040
Other: Indian Ocean Islander
BG0000
BG0011
BG0020
BG0030
BG0041
Other: Mauritius
BG0001
BG0010
BG0020
BG0030
BG0041
144.3
± 68.39
BG002187.4± 98.12
BG003151.0± 82.70
BG004145.9± 72.82
BG002249.8± 86.68
BG003226.0± 77.80
BG004216.6± 71.84
165.9
± 75.59
BG002189.4± 93.43
BG003163.4± 86.88
BG004159.6± 74.97
± 15.77
BG002129.4± 58.27
BG003103.6± 42.83
BG004104.7± 37.38
± 30.02
BG002154.0± 10.98
BG003154.8± 20.36
BG004142.7± 25.65
5
OG003-4.93± 7.660(7.660 to )
= 0.0056
Threshold for significance ≤ 0.05
LS Mean Difference
-43.28
Standard Error of the Mean
10.965
2-Sided
95
-69.21
17.35
Superiority
Participants with a GOFm in the PCSK9 gene or a LOFm in the Apo B gene (Cohort 2: Group C) received 150 mg alirocumab SC on days 1, 15, 29, 43, and 71 and matching placebo SC on days 57, 85, and 99. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
OG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2: Group D)
Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Units
Counts
Participants
OG0006
OG0017
OG0025
OG0035
Title
Denominators
Categories
Title
Measurements
OG000-53.33± 8.678(8.678 to )
OG001-3.78± 8.008(8.008 to )
OG002-47.73± 7.547(7.547 to )
OG003-3.09± 7.547(7.547 to )
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
LS means (SE), mean difference, 95% CI, and p-values were derived from ANCOVA with treatment group as factor and baseline as covariate.
ANCOVA
= 0.0021
Threshold for significance ≤ 0.05
LS Mean Difference
-49.55
Standard Error of the Mean
12.050
2-Sided
95
-76.39
-22.7
Superiority
OG002
OG003
LS means (SE), mean difference, 95% CI, and p-values were derived from ANCOVA with treatment group as factor and baseline as covariate.
ANCOVA
= 0.0045
Threshold for significance ≤ 0.05
LS Mean Difference
-44.64
Standard Error of the Mean
10.876
2-Sided
95
-70.36
18.92
Superiority
OG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2: Group D)
Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Units
Counts
Participants
OG0006
OG0017
OG0025
OG0035
Title
Denominators
Categories
Title
Measurements
OG000-56.87± 8.217(8.217 to )
OG001-7.50± 7.575(7.575 to )
OG002-44.40± 7.357(7.357 to )
OG003-4.04± 7.357(7.357 to )
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
= 0.0016
Threshold for significance ≤ 0.05
LS Mean Difference
-49.37
Standard Error of the Mean
11.487
2-Sided
95
-74.96
-23.77
Superiority
OG002
OG003
ANCOVA
= 0.0063
Threshold for significance ≤ 0.05
LS Mean Difference
-40.36
Standard Error of the Mean
10.471
2-Sided
95
-65.12
15.60
Superiority
OG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2: Group D)
Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.
Units
Counts
Participants
OG0006
OG0017
OG0025
OG0035
Title
Denominators
Categories
Title
Measurements
OG000-36.94± 5.203(5.203 to )
OG001-6.18± 4.802(4.802 to )
OG002-29.40± 4.422(4.422 to )
OG003-7.18± 4.422(4.422 to )
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
= 0.0017
Threshold for significance ≤ 0.05
LS Mean Difference
-30.75
Standard Error of the Mean
7.224
2-Sided
95
-46.85
-14.66
Superiority
OG002
OG003
ANCOVA
= 0.0096
Threshold for significance ≤ 0.05
LS Mean Difference
-22.23
Standard Error of the Mean
6.294
2-Sided
95
-37.11
-7.34
Superiority
OG003
PCSK9GOFm/ApoB LOFm: Alirocumab From Day 15(Cohort 2: Group D)
Participants with a GOFm in PCSK9 gene or LOFm in Apo B gene (Cohort 2: Group D) received 150 mg alirocumab SC on days 15, 29, 43, 57, and 85 and matching placebo SC on days 1, 71, and 99 during the double-blind period. Participants who continued in an open-label extension period received 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.