Study of REGN1500 in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

An Open-Label, Single-Arm, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Single and Multiple Doses of REGN1500 in Patients With Homozygous Familial Hypercholesterolemia

This is an open-label, single-arm study to assess the reduction of low-density lipoprotein cholesterol (LDL-C) by REGN1500 in patients with homozygous familial hypercholesterolemia (HoFH).

Study Overview

• Status: Completed
• Conditions: Homozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: REGN1500 250 mg SC/15 mg/kg IV/450 mg SC

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Chicoutimi, Quebec, Canada
• Netherlands
  • Amsterdam, Netherlands
• United States
  • California
    • Los Angeles, California, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • Texas
    • Dallas, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women ≥18 years of age at the time of the screening visit
2. Diagnosis of homozygous familial hypercholesterolemia (HoFH)
3. Willing to consistently maintain usual diet for the duration of the study

Exclusion Criteria:

1. Background medical lipid modifying therapy that has not been stable for at least 4 weeks (6 weeks for fibrates) prior to the screening visit
2. Having undergone lipid apheresis within 4 weeks prior to the screening visit
3. Use of another investigational drug or therapy within 30 days or at least 5 half-lives (whichever is longer) prior to the screening visit
4. Previous participation in any clinical trial of REGN1500

Note: The information listed above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial therefore not all inclusion/ exclusion criteria are listed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Open-label; Open-label REGN1500

Drug: REGN1500 250 mg SC/15 mg/kg IV/450 mg SC; Participants received single dose of REGN1500 subcutaneous (SC) injection of 250 milligrams (mg) at Week 0 (Day 1), followed by single dose of REGN1500 intravenous (IV) injection of 15 milligrams per kilogram (mg/kg) at Week 2 (Day 15) and then followed by 4 doses of REGN1500 SC injection of 450 mg once weekly starting from Week 12 (Day 85). Only the first 2 enrolled participants received 4 weekly REGN1500 450 mg SC doses at weeks 12, 13, 14, and 15 per the protocol. This dose regimen was removed under protocol amendment 4. Participants were followed for a period of 24 weeks (through Week 26 [Day 183]) after the last dose of study drug in the main study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 0) to Week 4 in the Main Study Period	Percent change was reported for low-density lipoprotein cholesterol (LDL-C) from baseline (week 0) up to week 4. LDL-C was measured using conventional units mg/dL. The efficacy analysis set included all participants in the safety analysis set (SAF) who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 0) to Week 4 in the Main Study Period	Absolute change in low-density lipoprotein cholesterol (LDL-C) from baseline (week 0) up to week 4 was reported. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 4
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Week 2 to Week 4 in the Main Study Period	Absolute change in low-density lipoprotein cholesterol (LDL-C) from week 2 to week 4 was reported. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Week 2 to Week 4
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Week 2 to Week 4 in the Main Study Period	Percent change was reported in low-density lipoprotein cholesterol (LDL-C) from week 2 to week 4. LDL-C was measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Week 2 to Week 4
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 0) Over Time in the Main Study Period	Absolute change was reported in low-density lipoprotein cholesterol (LDL-C) from baseline (week 0) up to week 26. The efficacy analysis set included all participants in the safety analysis set (SAF) who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 26
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 0) Over Time in the Main Study Period	Percent change was reported in low-density lipoprotein cholesterol (LDL-C) from baseline (week 0) up to week 26. LDL-C was measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 26
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 26) to Week 214 in the Open Label Extension (OLE) Period	Absolute change in low-density lipoprotein cholesterol (LDL-C) from baseline (week 26) up to week 214 was reported. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period. (ET= Early Termination; EOS = End of Study)	Baseline (Week 26) up to Week 214
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline (Week 26) to Week 214 in the Open Label Extension (OLE) Period	Percent change was reported in low-density lipoprotein cholesterol (LDL-C) from baseline (week 26) to week 214 in the OLE period. LDL-C was measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had at least 1 post-baseline measure of the lipid panel in the main study period. (ET= Early Termination; EOS = End of Study)	Baseline (Week 26) up to Week 214
Absolute Change in Apolipoprotein (Apo B), Non-High-Density Lipoprotein Cholesterol (Non-HDL-C), Total Cholesterol (Total-C), and Lipoprotein(a) (Lp[a]) From Baseline (Week 0) up to Week 26 in the Main Study Period	Absolute change was reported for Apo B, Non-HDL-C, Total-C, and Lp(a) from baseline (week 0) up to Week 26. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 26
Percent Change in Apolipoprotein (Apo B), Non-High-Density Lipoprotein Cholesterol (Non-HDL-C), Total Cholesterol (Total-C), and Lipoprotein(a) (Lp[a]) From Baseline (Week 0) up to Week 26 in the Main Study Period	Percent change was reported for Apo B, Non-HDL-C, Total-C, and Lp(a) from baseline (week 0) up to week 26. Apo B, Non-HDL-C, Total-C, and Lp(a) were measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 26
Absolute Change in Apolipoprotein (Apo B), Non-High-Density Lipoprotein Cholesterol (Non-HDL-C), Total Cholesterol (Total-C), and Lipoprotein(a) (Lp[a]) From Baseline (Week 26) to Week 214 in the Open Label Extension (OLE) Period	Absolute changein Apo B, Non-HDL-C, Total-C, and Lp(a) from baseline to week 214 in open label extension (OLE) period. The efficacy analysis set included all participants in the SAF who had baseline and at least one post-baseline measure of the lipid panel in the main study period. (ET = Early Termination; EOS = End of Study)	Baseline (Week 26) up to Week 214
Percent Change in Apolipoprotein (Apo B), Non-High-Density Lipoprotein Cholesterol (Non-HDL-C), Total Cholesterol (Total-C), and Lipoprotein(a) (Lp[a]) From Baseline (Week 26) to Week 214 in the Open Label Extension (OLE) Period	Percent change was reported in Apo B, Non-HDL-C, Total-C, and Lp(a) from baseline (week 26) up to week 214 in OLE Period. Apo B, Non-HDL-C, Total-C, and Lp(a) were measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had baseline and at least one post-baseline measure of the lipid panel in the main study period. (ET= Early Termination; EOS = End of Study)	Baseline (Week 26) up to Week 214
Percentage of Participants Who Achieved Reduction in Low-Density Lipoprotein Cholesterol (LDL-C) of ≥ 25% From Baseline (Week 0) in the Main Study Period	Percentage of participants who achieved reduction in low-density lipoprotein cholesterol (LDL-C) of greater than or equal to (≥) 25 percent (%) from baseline in the main study period was reported. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 26
Percentage of Participants Who Achieved Reduction in Low-Density Lipoprotein Cholesterol (LDL-C) of ≥ 25% From Baseline (Week 26) in the Open Label Extension (OLE) Period	Percentage of participants who achieved a reduction in low-density lipoprotein cholesterol (LDL-C) of ≥ 25% from baseline (week 26) to week 214 was reported. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 26) to Week 214
Percentage of Participants Who Achieved Reduction in Low-Density Lipoprotein Cholesterol (LDL-C) of ≥ 50% From Baseline (Week 0) in the Main Study Period	Percentage of participants who achieved a reduction in low-density lipoprotein cholesterol (LDL-C) of ≥ 50% from baseline (week 0) to week 26 was reported. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) to Week 26
Percentage of Participants Who Achieved Reduction in Low-Density Lipoprotein Cholesterol (LDL-C) of ≥ 50% From Baseline (Week 26) in the Open Label Extension (OLE) Period	Percentage of participants who achieved reduction in low-density lipoprotein cholesterol (LDL-C) of ≥ 50% from baseline (week 26) in the OLE period was reported. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 26) up to Week 214
Absolute Change in High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), and Apolipoprotein A-1 (Apo A-1) From Baseline (Week 0) Over Time in the Main Study Period	Absolute change was reported in HDL-C, TG, and Apo A-1 from baseline (week 0) up to week 26. The efficacy analysis set included all participants in the SAF who had baseline and at least one post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 26
Percent Change in High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), and Apolipoprotein A-1 (Apo A-1) From Baseline (Week 0) Over Time in the Main Study Period	Percent change was reported in HDL-C, TG, and Apo A-1 from baseline (week 0) up to week 26. HDL-C, TG, and Apo A-1 were measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 26
Percent Change in High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), and Apolipoprotein A-1 (Apo A-1) From Baseline (Week 26) to Week 214 in the Open Label Extension (OLE) Period	Percent change was reported in HDL-C, TG and Apo A-1 from baseline (week 26) up to week 214. HDL-C, TG and Apo A-1 were measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had baseline and at least one post-baseline measure of the lipid panel in the main study period. (ET= Early Termination; EOS = End of Study)	Baseline (Week 26) up to Week 214
Absolute Change in High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), and Apolipoprotein A-1 (Apo A-1) From Baseline (Week 26) to Week 214 in the Open Label Extension (OLE) Period	Absolute change was reported in HDL-C, TG and Apo A-1 from baseline (week 26) up to week 214. The efficacy analysis set included all participants in the SAF who had baseline and at least one post-baseline measure of the lipid panel in the main study period. (ET= Early Termination; EOS = End of Study)	Baseline (Week 26) up to Week 214
Absolute Change in Apolipoprotein CIII (Apo CIII) From Baseline (Week 0) Over Time in the Main Study Period	Absolute change was reported in Apo CIII from baseline (week 0) up to week 16. The efficacy analysis set included all participants in the SAF who had baseline and at least 1 post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) up to Week 16
Percent Change in Apolipoprotein CIII (Apo CIII) From Baseline (Week 0) Over Time in the Main Study Period	Percent change was reported in Apo CIII from baseline (week 0) up to week 16. Apo CIII was measured using conventional units mg/dL. The efficacy analysis set included all participants in the SAF who had baseline and at least one post-baseline measure of the lipid panel in the main study period.	Baseline (Week 0) to Week 16

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Gaudet D, Gipe DA, Pordy R, Ahmad Z, Cuchel M, Shah PK, Chyu KY, Sasiela WJ, Chan KC, Brisson D, Khoury E, Banerjee P, Gusarova V, Gromada J, Stahl N, Yancopoulos GD, Hovingh GK. ANGPTL3 Inhibition in Homozygous Familial Hypercholesterolemia. N Engl J Med. 2017 Jul 20;377(3):296-297. doi: 10.1056/NEJMc1705994. No abstract available.
• Banerjee P, Chan KC, Tarabocchia M, Benito-Vicente A, Alves AC, Uribe KB, Bourbon M, Skiba PJ, Pordy R, Gipe DA, Gaudet D, Martin C. Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants in Patient Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of LDLR Activity. Arterioscler Thromb Vasc Biol. 2019 Nov;39(11):2248-2260. doi: 10.1161/ATVBAHA.119.313051. Epub 2019 Oct 3.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2015
• Primary Completion (Actual): November 21, 2016
• Study Completion (Actual): July 23, 2018

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: October 10, 2014
• First Posted (Estimate): October 16, 2014

Study Record Updates

• Last Update Posted (Actual): December 9, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: R1500-CL-1331; 2016-000411-32 (EudraCT Number)