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

Homozygous Familial Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02265952
• Other study ID #: R1500-CL-1331
• Secondary ID: 2016-000411-32
• Status: Completed
• Phase: Phase 2
• Start date: February 4, 2015
• Est. completion date: July 23, 2018

Study information

• Verified date: December 2019
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: July 23, 2018
• Est. primary completion date: November 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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