Clinical trial 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)
Official title: A Phase 2, Open-Label Extension of Study R727-CL-1003 to Evaluate the Long-Term Safety and Efficacy of REGN727 Administered by Subcutaneous Injection in Patients With Heterozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2012-04-12
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Key Inclusion Criteria:

1. Prior participation in and the successful completion of the R727-CL-1003 study (NCT01266876).
2. Patients must be on a stable daily statin regimen for at least 3 weeks before prior to entry into the study
3. A negative urine pregnancy at the screening/baseline visit for women of childbearing potential

Key Exclusion Criteria:

1. Reported a drug-related serious adverse event (SAE) or drug-related clinical or laboratory adverse event (AE) in the R727-CL-1003 study that resulted in early termination or withdrawal
2. Significant protocol deviation in R727-CL-1003, such as non-compliance by the investigator or patient
3. Low-density lipoprotein (LDL) apheresis within 12 months before the screening/baseline visit

Note: Other exclusion criteria applied

Primary outcomes:
measure: Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
timeFrame: Baseline (Day 1 of current study) to end of study (Week 218)
Secondary outcomes:
measure: Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Week 24
timeFrame: Baseline (current study) to Week 24
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 12
timeFrame: Baseline (current study) up to Week 12
measure: Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 24
timeFrame: Baseline(current study) up to Week 24
measure: Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 12
timeFrame: Baseline (current study) up to Week 12
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 52
timeFrame: Baseline (current study) up to Week 52
measure: 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
timeFrame: At Week 24
measure: Percent Change in Lipoprotein a (Lp[a]) at Week 24
timeFrame: At Week 24
measure: Percent Change in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and Week 12
timeFrame: At Week 24 and 12
measure: Percent Change in Lipoprotein a at Week 12
timeFrame: At Week 12
measure: Percent Change in Triglycerides (TG) at Week 24 and Week 12
timeFrame: At Week 24 and 12
measure: Percent Change in Apolipoprotein A-1 (Apo A-1) at Week 24 and Week 12
timeFrame: At Week 24 and Week 12
measure: Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to the End of Treatment
timeFrame: Baseline (current study) to the End of Treatment (Week 208)
measure: Percentage of Participants With Low Density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 Milligrams Per Deciliter (mg/dL) for Prior MI/Stroke, or <100 mg/dL [2.59 mmol/L] for Participants Without Prior MI/Stroke at Week 12, 52 and End of Treatment
timeFrame: At Week 12, 52 and End of Treatment (Week 208)
measure: Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Weeks 12, 24, 52, and End of Treatment
timeFrame: Baseline (current study) to Weeks 12, 24, 52, and End of Treatment (Week 208)
measure: Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Lipoprotein a (Lp[a]), HDL-C, Triglycerides, and Apolipoprotein A-1 From Baseline in Current Study to Week 52 and End of Treatment
timeFrame: Baseline (current study) up to Weeks 52 and End of Treatment (Week 208)
measure: Change in Ratio in Apolipoprotein (Apo) B/Apo A-1 From Baseline in Current Study to Week 12, 24, 52, and End of Treatment.
timeFrame: Baseline (current study) to Weeks 12, 24, 52, and End of Treatment (Week 208)
measure: Percentage of Participants With Apolipoprotein (Apo) B <80 mg/dL at Week 12, 24, 52, and End of Treatment
timeFrame: At Week 12, 24, 52, and End of Treatment (Week 208)
measure: Percentage of Participants With Non-High Density Lipoprotein Cholesterol (HDL-C) <100 mg/dL (2.59 mmol/L) at Week 12, 24, 52, and End of Treatment
timeFrame: At Week 12, 24, 52, and End of Treatment (Week 208)
measure: Percentage of Participants With Low Density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 Milligrams Per Deciliter (mg/dL) and/or ≥ 50% Reduction in LDL-C (if LDL-C >70 mg/dL [1.81 mmol/L]) at Week 12, 24, 52, and End of Treatment
timeFrame: At Week 12, 24, 52, and End of Treatment (Week 208)
Other outcomes:
Locations:
city: Mission Viejo
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Kansas City
country: United States
state: Kansas
city: Auburn
country: United States
state: Maine
city: Saint Louis
country: United States
state: Missouri
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Chicoutimi
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Sainte-Foy
country: Canada
state: Quebec
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Dufour R, Bergeron J, Gaudet D, Weiss R, Hovingh GK, Qing Z, Yang F, Andisik M, Torri A, Pordy R, Gipe DA. Open-label therapy with alirocumab in patients with heterozygous familial hypercholesterolemia: Results from three years of treatment. Int J Cardiol. 2017 Feb 1;228:754-760. doi: 10.1016/j.ijcard.2016.11.046. Epub 2016 Nov 9.