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NCT01576484

Open-Label Extension of Study R727-CL-1003 (NCT01266876) to Evaluate the Long-Term Safety and Efficacy of Alirocumab (REGN727) in Participants With Heterozygous Familial Hypercholesterolemia (HeFH)

Completed Phase 2 Results posted Last updated 5 August 2020
What this trial tests

Phase 2 trial testing Alirocumab in Hypercholesterolemia in 58 participants. Completed in 22 December 2016.

Timeline
28 February 2012
Primary endpoint
22 December 2016
22 December 2016

Quick facts

Lead sponsorRegeneron Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment58
Start date28 February 2012
Primary completion22 December 2016
Estimated completion22 December 2016
Sites14 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Hypercholesterolemia or Heterozygous Familial Hypercholesterolemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death Primary · Baseline (Day 1 of current study) to end of study (Week 218)

An AE was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. Treatment- emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on- treatment period (time from the first dose of study drug to the last dose of study drug plus 70 days). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, pers

Adverse Events
GroupValue95% CI
Placebo Participants in Parent Study12
Participants Previously Exposed to Alirocumab in Parent Study42
All Participants54
Serious Adverse Events
GroupValue95% CI
Placebo Participants in Parent Study4
Participants Previously Exposed to Alirocumab in Parent Study8
All Participants12
Adverse Events Leading to Death
GroupValue95% CI
Placebo Participants in Parent Study0
Participants Previously Exposed to Alirocumab in Parent Study0
All Participants0
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Week 24 Secondary · Baseline (current study) to Week 24

Percent change for serum LDL-C (Low-density lipoprotein cholesterol) from baseline to Week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study.

GroupValue95% CI
Placebo Participants in Parent Study-73.15± 15.01
Participants Previously Exposed to Alirocumab in Parent Study-63.40± 22.04
All Participants-65.35± 21.07
Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 12 Secondary · Baseline (current study) up to Week 12

Percent change for serum LDL-C (Low-density lipoprotein cholesterol) from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study.

GroupValue95% CI
Placebo Participants in Parent Study-55.93± 29.53
Participants Previously Exposed to Alirocumab in Parent Study-63.94± 23.35
All Participants-62.22± 24.73
Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 24 Secondary · Baseline(current study) up to Week 24

Percent change for Apo B, Non-HDL-C and Total Cholesterol from baseline to Week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study.

Apo B
GroupValue95% CI
Placebo Participants in Parent Study-52.23± 20.30
Participants Previously Exposed to Alirocumab in Parent Study-50.52± 18.18
All Participants-50.86± 18.43
Non-HDL-C
GroupValue95% CI
Placebo Participants in Parent Study-56.75± 21.80
Participants Previously Exposed to Alirocumab in Parent Study-55.43± 20.97
All Participants-55.71± 20.95
Total cholesterol
GroupValue95% CI
Placebo Participants in Parent Study-42.72± 15.30
Participants Previously Exposed to Alirocumab in Parent Study-41.47± 16.37
All Participants-41.74± 16.02
Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 12 Secondary · Baseline (current study) up to Week 12

Percent change for serum Apo B, Non-HDL-C, and Total Cholesterol from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study.

Apo- B
GroupValue95% CI
Placebo Participants in Parent Study-40.69± 30.46
Participants Previously Exposed to Alirocumab in Parent Study-48.78± 20.24
All Participants-47.16± 22.56
Non-HDL- C
GroupValue95% CI
Placebo Participants in Parent Study-47.81± 32.92
Participants Previously Exposed to Alirocumab in Parent Study-54.97± 22.85
All Participants-53.44± 25.18
Total Cholesterol
GroupValue95% CI
Placebo Participants in Parent Study-36.78± 24.88
Participants Previously Exposed to Alirocumab in Parent Study-40.47± 16.93
All Participants-39.68± 18.72
Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 52 Secondary · Baseline (current study) up to Week 52

Percent change for serum LDL-C from baseline to Week 52 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study.

GroupValue95% CI
Placebo Participants in Parent Study-54.57± 26.20
Participants Previously Exposed to Alirocumab in Parent Study-55.67± 34.41
All Participants-55.43± 32.53
Percentage of Participants With Low Density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 Milligrams Per Deciliter (mg/dL) for Prior Myocardial Infarction (MI)/Stroke, or <100 mg/dL [2.59 mmol/L] for Participants Without Prior MI/Stroke at Week 24 Secondary · At Week 24

Percentage of participants reaching LDL-C goal (ie, LDL-C \<70 mg/dL (1.81 millimoles per liter \[mmol/L\]) in case of prior MI/stroke, or \<100 mg/dL \[2.59 mmol/L\] for participants without prior MI/stroke) at week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, were reported.

GroupValue95% CI
Placebo Participants in Parent Study100.00
Participants Previously Exposed to Alirocumab in Parent Study90.91
All Participants92.73
Percent Change in Lipoprotein a (Lp[a]) at Week 24 Secondary · At Week 24

Percent change in serum lipoprotein a at week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported.

GroupValue95% CI
Placebo Participants in Parent Study-27.91± 23.62
Participants Previously Exposed to Alirocumab in Parent Study-29.41± 25.01
All Participants-29.11± 24.53
Percent Change in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and Week 12 Secondary · At Week 24 and 12

Percent change for serum High Density Lipoprotein Cholesterol (HDL-C) in the current study at weeks 24 and week 12, during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported.

Week 24
GroupValue95% CI
Placebo Participants in Parent Study2.61± 15.75
Participants Previously Exposed to Alirocumab in Parent Study7.14± 16.04
All Participants6.17± 15.94
Week 12
GroupValue95% CI
Placebo Participants in Parent Study1.46± 14.08
Participants Previously Exposed to Alirocumab in Parent Study10.43± 15.98
All Participants8.51± 15.91
Percent Change in Lipoprotein a at Week 12 Secondary · At Week 12

Percent change for serum Lipoprotein a at Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported.

GroupValue95% CI
Placebo Matched to R727-20.30± 24.10
Participants Previously Exposed to Alirocumab in Parent Study-26.98± 22.71
All Participants-25.64± 22.92
Percent Change in Triglycerides (TG) at Week 24 and Week 12 Secondary · At Week 24 and 12

Percent change for serum TG at Week 24 and Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported.

Week 24
GroupValue95% CI
Placebo Participants in Parent Study0.19± 54.71
Participants Previously Exposed to Alirocumab in Parent Study-2.01± 41.22
All Participants-1.54± 43.91
Week 12
GroupValue95% CI
Placebo Participants in Parent Study-6.40± 46.11
Participants Previously Exposed to Alirocumab in Parent Study0.52± 34.17
All Participants-0.96± 36.69
Percent Change in Apolipoprotein A-1 (Apo A-1) at Week 24 and Week 12 Secondary · At Week 24 and Week 12

Percent change for serum Apo A-1 at Week 24 and Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported.

Week 24
GroupValue95% CI
Placebo Participants in Parent Study5.41± 11.96
Participants Previously Exposed to Alirocumab in Parent Study4.78± 11.20
All Participants4.91± 11.24
Week 12
GroupValue95% CI
Placebo Participants in Parent Study11.10± 11.43
Participants Previously Exposed to Alirocumab in Parent Study8.64± 10.99
All Participants9.13± 11.02

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 218) regardless of seriousness or relationship to investigational product.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Participants in Parent Study
Serious: 4/12 (33%)
Deaths: 0/12
Participants Previously Exposed to Alirocumab in Parent Study
Serious: 8/46 (17%)
Deaths: 0/46

Serious adverse events (14 terms)

ReactionSystemPlacebo Participants in Pa…Participants Previously Ex…
Angina unstableCardiac disorders——
Aortic valve stenosisCardiac disorders——
Atrial fibrillationCardiac disorders——
Atrial flutterCardiac disorders——
Coronary artery diseaseCardiac disorders——
Colitis ischaemicGastrointestinal disorders——
Gastrooesophageal reflux diseaseGastrointestinal disorders——
Intestinal obstructionGastrointestinal disorders——
Gastrointestinal viral infectionInfections and infestations——
Thermal burnInjury, poisoning and procedural complications——
OsteoarthritisMusculoskeletal and connective tissue disorders——
AmnesiaNervous system disorders——
Carotid artery diseaseNervous system disorders——
Neuropsychiatric symptomsPsychiatric disorders——
Other adverse events (107 terms — click to expand)

ReactionSystemPlacebo Participants in Pa…Participants Previously Ex…
Upper respiratory tract infectionInfections and infestations——
NasopharyngitisInfections and infestations——
BronchitisInfections and infestations——
HeadacheNervous system disorders——
Back painMusculoskeletal and connective tissue disorders——
ArthralgiaMusculoskeletal and connective tissue disorders——
MyalgiaMusculoskeletal and connective tissue disorders——
Injection site haemorrhageGeneral disorders——
DiarrhoeaGastrointestinal disorders——
Injection site bruisingGeneral disorders——
DizzinessNervous system disorders——
VomitingGastrointestinal disorders——
GastroenteritisInfections and infestations——
InfluenzaInfections and infestations——
SinusitisInfections and infestations——
Urinary tract infectionInfections and infestations——
Ligament sprainInjury, poisoning and procedural complications——
AnxietyPsychiatric disorders——
CoughRespiratory, thoracic and mediastinal disorders——
HypertensionVascular disorders——
Injection site painGeneral disorders——
OsteoarthritisMusculoskeletal and connective tissue disorders——
Pain in extremityMusculoskeletal and connective tissue disorders——
Gastrooesophageal reflux diseaseGastrointestinal disorders——
NauseaGastrointestinal disorders——
FatigueGeneral disorders——
Seasonal allergyImmune system disorders——
ConjunctivitisInfections and infestations——
Gastroenteritis viralInfections and infestations——
Tooth infectionInfections and infestations——
Procedural painInjury, poisoning and procedural complications——
Musculoskeletal painMusculoskeletal and connective tissue disorders——
Neck painMusculoskeletal and connective tissue disorders——
TendonitisMusculoskeletal and connective tissue disorders——
DepressionPsychiatric disorders——
Oropharyngeal painRespiratory, thoracic and mediastinal disorders——
UrticariaSkin and subcutaneous tissue disorders——
AnaemiaBlood and lymphatic system disorders——
Abdominal painGastrointestinal disorders——
Injection site erythemaGeneral disorders——

Most-reported serious reactions: Angina unstable, Aortic valve stenosis, Atrial fibrillation, Atrial flutter, Coronary artery disease, Colitis ischaemic, Gastrooesophageal reflux disease, Intestinal obstruction.

Data from ClinicalTrials.gov NCT01576484 adverse events section.

Sponsor's own description

The primary objective of the study was to assess the long-term safety and tolerability of alirocumab in patients with heFH who were receiving concomitant treatment with hydroxymethyl glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), with or without other lipid-modifying therapies (LMTs).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Population Pharmacokinetic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using a Michaelis-Menten Approximation of a Target-Mediated Drug Disposition Model-Support for a Biologics License Application Submission: Part I.
    Martinez JM, Brunet A, Hurbin F, DiCioccio AT, et al · · 2019 · cited 23× · PMID 29725996 · DOI 10.1007/s40262-018-0669-y
  2. Open-label therapy with alirocumab in patients with heterozygous familial hypercholesterolemia: Results from three years of treatment.
    Dufour R, Bergeron J, Gaudet D, Weiss R, et al · · 2017 · cited 14× · PMID 27886619 · DOI 10.1016/j.ijcard.2016.11.046

Verify or expand the search:

Other trials of Alirocumab

Trials testing the same drug.

Other recruiting trials for Hypercholesterolemia

Currently open trials in the same condition.

Other Regeneron Pharmaceuticals trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01576484.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing