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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)

Primary Purpose

Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Alirocumab

Placebo Matched to Alirocumab

About this trial

This is an interventional treatment trial for Hypercholesterolemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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

Key Exclusion Criteria:

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
Significant protocol deviation in R727-CL-1003, such as non-compliance by the investigator or patient
Low-density lipoprotein (LDL) apheresis within 12 months before the screening/baseline visit

Note: Other exclusion criteria applied

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo Matched to Alirocumab

Alirocumab 150 mg

Arm Description

Participants who received placebo in parent study (NCT01576484), has received a subcutaneous injection of placebo matched to alirocumab every 2 weeks for 4 years in this study.

Participants who received alirocumab in parent study (NCT01576484), has received a subcutaneous injection of alirocumab 150 milligram (mg) every 2 weeks for 4 years in this study.

Outcomes

Primary Outcome Measures

Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death

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, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.

Secondary Outcome Measures

Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the 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.

Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study 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.

Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study 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.

Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study 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.

Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study 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.

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

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.

Percent Change in Lipoprotein a (Lp[a]) 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.

Percent Change in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and Week 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.

Percent Change in Lipoprotein a 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.

Percent Change in Triglycerides (TG) at Week 24 and Week 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.

Percent Change in Apolipoprotein A-1 (Apo A-1) 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.

Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to the End of Treatment

Percent change for serum LDL-C from baseline to Week 208 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.

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

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 12, 52 and end of treatment, 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.

Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Weeks 12, 24, 52, and End of Treatment

Absolute change was reported for serum LDL-C from baseline to weeks 12, 24, 52, and end of Treatment (Week 208) 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.

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

Percent change was reported for serum (Apo B), non-HDL-C, total-C, Lp(a), HDL-C, TG, and Apo A-1 from baseline to weeks 52 and end of treatment (Week 208) 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.

Change in Ratio in Apolipoprotein (Apo) B/Apo A-1 From Baseline in Current Study to Week 12, 24, 52, and End of Treatment.

Change in ratio in Apolipoprotein (Apo) B/Apo A-1 from baseline in current Study to week 12, 24, 52, and end of treatment (Week 208) 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.

Percentage of Participants With Apolipoprotein (Apo) B <80 mg/dL at Week 12, 24, 52, and End of Treatment

Percentage of participants was calculated with Apo B <80 mg/dL (0.8 mmol/L) at week 12, 24, 52, and End of Treatment (Week 208) 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.

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

Percentage of participants was calculated with non-HDL-C <100 mg/dL (2.59 mmol/L) at Weeks 12, 24, 52, and End of Treatment (Week 208) 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.

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

Percentage of Participants was calculated with LDL-C <70 mg/dL (1.81 mmol/L) and/or ≥ 50% Reduction in LDL-C (if LDL-C >70 mg/dL [1.81 mmol/L]) at Weeks 12, 24, 52, and End of Treatment (Week 208) 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.

Full Information

NCT ID

NCT01576484

First Posted

March 27, 2012

Last Updated

July 19, 2020

Sponsor

Regeneron Pharmaceuticals

Collaborators

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT01576484

Brief Title

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

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

February 28, 2012 (Actual)

Primary Completion Date

December 22, 2016 (Actual)

Study Completion Date

December 22, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

Collaborators

Sanofi

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

58 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo Matched to Alirocumab

Arm Type

Placebo Comparator

Arm Description

Participants who received placebo in parent study (NCT01576484), has received a subcutaneous injection of placebo matched to alirocumab every 2 weeks for 4 years in this study.

Arm Title

Alirocumab 150 mg

Arm Type

Experimental

Arm Description

Participants who received alirocumab in parent study (NCT01576484), has received a subcutaneous injection of alirocumab 150 milligram (mg) every 2 weeks for 4 years in this study.

Intervention Type

Drug

Intervention Name(s)

Alirocumab

Other Intervention Name(s)

REGN727, SAR236553, PRALUENT

Intervention Description

Alirocumab was supplied in a pre-filled syringe and administered subcutaneously (SC) in the abdomen, thigh, or outer upper arm; REGN727(SAR236553) is an anti-PCSK9 (proprotein convertase subtilisin/kexin type 9) antibody

Intervention Type

Drug

Intervention Name(s)

Placebo Matched to Alirocumab

Intervention Description

Placebo matched to alirocumab was supplied in a pre-filled syringe and administered subcutaneously (SC) in the abdomen, thigh, or outer upper arm; REGN727(SAR236553) is an anti-PCSK9 (proprotein convertase subtilisin/kexin type 9) antibody

Primary Outcome Measure Information:

Title

Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death

Description

Time Frame

Baseline (Day 1 of current study) to end of study (Week 218)

Secondary Outcome Measure Information:

Title

Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Week 24

Description

Time Frame

Baseline (current study) to Week 24

Title

Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 12

Description

Time Frame

Baseline (current study) up to Week 12

Title

Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 24

Description

Time Frame

Baseline(current study) up to Week 24

Title

Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 12

Description

Time Frame

Baseline (current study) up to Week 12

Title

Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 52

Description

Time Frame

Baseline (current study) up to Week 52

Title

Description

Time Frame

At Week 24

Title

Percent Change in Lipoprotein a (Lp[a]) at Week 24

Description

Time Frame

At Week 24

Title

Percent Change in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and Week 12

Description

Time Frame

At Week 24 and 12

Title

Percent Change in Lipoprotein a at Week 12

Description

Time Frame

At Week 12

Title

Percent Change in Triglycerides (TG) at Week 24 and Week 12

Description

Time Frame

At Week 24 and 12

Title

Percent Change in Apolipoprotein A-1 (Apo A-1) at Week 24 and Week 12

Description

Time Frame

At Week 24 and Week 12

Title

Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to the End of Treatment

Description

Time Frame

Baseline (current study) to the End of Treatment (Week 208)

Title

Description

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 12, 52 and end of treatment, 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.

Time Frame

At Week 12, 52 and End of Treatment (Week 208)

Title

Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Weeks 12, 24, 52, and End of Treatment

Description

Time Frame

Baseline (current study) to Weeks 12, 24, 52, and End of Treatment (Week 208)

Title

Description

Time Frame

Baseline (current study) up to Weeks 52 and End of Treatment (Week 208)

Title

Change in Ratio in Apolipoprotein (Apo) B/Apo A-1 From Baseline in Current Study to Week 12, 24, 52, and End of Treatment.

Description

Time Frame

Baseline (current study) to Weeks 12, 24, 52, and End of Treatment (Week 208)

Title

Percentage of Participants With Apolipoprotein (Apo) B <80 mg/dL at Week 12, 24, 52, and End of Treatment

Description

Time Frame

At Week 12, 24, 52, and End of Treatment (Week 208)

Title

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

Description

Time Frame

At Week 12, 24, 52, and End of Treatment (Week 208)

Title

Description

Time Frame

At Week 12, 24, 52, and End of Treatment (Week 208)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Prior participation in and the successful completion of the R727-CL-1003 study (NCT01266876). Patients must be on a stable daily statin regimen for at least 3 weeks before prior to entry into the study A negative urine pregnancy at the screening/baseline visit for women of childbearing potential Key Exclusion Criteria: 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 Significant protocol deviation in R727-CL-1003, such as non-compliance by the investigator or patient Low-density lipoprotein (LDL) apheresis within 12 months before the screening/baseline visit Note: Other exclusion criteria applied

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Management

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

City

Mission Viejo

State/Province

California

Country

United States

City

Newport Beach

State/Province

California

Country

United States

City

Thousand Oaks

State/Province

California

Country

United States

City

Miami

State/Province

Florida

Country

United States

City

Port Orange

State/Province

Florida

Country

United States

City

Kansas City

State/Province

Kansas

Country

United States

City

Auburn

State/Province

Maine

Country

United States

City

Saint Louis

State/Province

Missouri

Country

United States

City

Durham

State/Province

North Carolina

Country

United States

City

Cincinnati

State/Province

Ohio

Country

United States

City

Houston

State/Province

Texas

Country

United States

City

Chicoutimi

State/Province

Quebec

Country

Canada

City

Montreal

State/Province

Quebec

Country

Canada

City

Sainte-Foy

State/Province

Quebec

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

27886619

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.

Results Reference

derived

Learn more about this trial

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)

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