Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, 12-Week Study of the Safety and Efficacy of REGN727 in Patients With Heterozygous Familial Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01266876
• Other study ID #: R727-CL-1003
• Status: Completed
• Phase: Phase 2
• First received: December 23, 2010
• Last updated: August 20, 2015
• Start date: January 2011
• Est. completion date: November 2011

Study information

• Verified date: August 2015
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Must meet the World Health Organization criteria for heFH

2. Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening

3. Serum LDL-C levels = 100 mg/dL at screening

4. Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit

5. A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential

Key Exclusion Criteria:

1. Participants with homozygous FH (clinically or by previous genotyping)

2. Use of a medication (other than a statin or EZE) to alter serum lipids within 42 days (6 weeks) before screening including, but not limited to:

• Fibrates

• Niacin (>500 mg/day)

• Omega-3 fatty acids (>1000 mg/day of DHA/EPA)

• Bile acid resins

3. Use of nutraceuticals or OTC medications that may alter lipid levels that are not stable for at least 6 weeks before screening and are not planned to remain constant throughout the study. Examples include:

• Omega-3 fatty acids (=1000 mg/day of DHA/EPA)

• Niacin (=500 mg/day)

• Plant stanols, such as found in Benecol, flax seed oil, psyllium

• Red yeast rice

4. Disorders known to influence lipid levels, such as nephrotic syndrome, significant liver disease, Cushing's disease, untreated hypothyroidism (patients on stable thyroid replacement for at least 12 weeks before the full screening visit, who are metabolically euthyroid by thyroid-stimulating hormone (TSH) testing are allowed)

5. Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit)

6. Fasting serum TG >350 mg/dL screening

7. LDL apheresis within 12 months before screening

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab
Alirocumab two SC injections in the abdomen only.
• Placebo
Placebo two SC injections in the abdomen only.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis	Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis	Calculated LDL-C value was obtained from Friedewald formula. Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis	Calculated LDL-C value was obtained from Friedewald formula.	Week 12 (LOCF)	No
Secondary	Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis	Calculated LDL-C value was obtained from Friedewald formula.	Week 12 (LOCF)	No
Secondary	Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint..	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range)	From Baseline to Week 12 (LOCF)	No
Secondary	Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12	No
Secondary	Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12	No
Secondary	Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 12	No
Secondary	Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range)	From Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range)	From Baseline to Week 12 (LOCF)	No