Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Five Doses and Two Dose Regimens of SAR236553 Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥ 2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01288443
• Other study ID #: DFI11565
• Secondary ID: U1111-1116-5252
• Status: Completed
• Phase: Phase 2
• First received: February 1, 2011
• Last updated: August 21, 2015
• Start date: January 2011
• Est. completion date: December 2011

Study information

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

Clinical Trial Summary

Primary Objective:

• To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy.

Secondary Objectives:

• To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo

• To evaluate the safety and tolerability of alirocumab

• To evaluate the development of anti-alirocumab antibodies

• To evaluate the pharmacokinetics of alirocumab

Description:

The duration of study participation depended on the status of the participant at screening:

• For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks.

• For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

• Participants with primary hypercholesterolemia receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period or drug naive participants if they are likely to have low-density lipoprotein cholesterol (LDL-C) = 100 mg/dL (= 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy

OR

• Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period and likely to have LDL-C = 100 mg/dL (= 2.59 mmol/L) at the screening visit

Exclusion criteria:

1. LDL-C < 100 mg/dL (< 2.59 mmol/L):

• After the run-in period on atorvastatin (10 mg, 20 mg, or 40 mg) for participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to the screening, or drug naive participant

OR

• At the first visit for participants who were being treated with stable dose of atorvastatin (10 mg, 20 mg, or 40 mg) for at least 6 weeks prior to screening

2. Participants not previously instructed on a cholesterol-lowering diet

3. Participants with type 1 diabetes

4. Participants with type 2 diabetes treated with insulin

5. Participants with type 2 diabetes and with an glycated hemoglobin (HbA1c) = 8.5% at screening visit (considered poorly controlled)

6. Laboratory findings measured before randomization:

• Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at screening visit

• Positive serum or urine pregnancy test in females of childbearing potential

7. Pregnant or breast-feeding women

8. Women of childbearing potential with no effective contraceptive method

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Design

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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab
Two SC injections in the abdomen only.
• Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only.
• Atorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Locations

Country	Name	City	State
United States	Investigational Site Number 840535	Auburn	Maine
United States	Investigational Site Number 840504	Aventura	Florida
United States	Investigational Site Number 840519	Aventura	Florida
United States	Investigational Site Number 840531	Bountiful	Utah
United States	Investigational Site Number 840521	Bristol	Tennessee
United States	Investigational Site Number 840503	Brockton	Massachusetts
United States	Investigational Site Number 840527	Chicago	Illinois
United States	Investigational Site Number 840511	Cincinnati	Ohio
United States	Investigational Site Number 840526	Cincinnati	Ohio
United States	Investigational Site Number 840530	Colorado Springs	Colorado
United States	Investigational Site Number 840505	Edison	New Jersey
United States	Investigational Site Number 840537	Eugene	Oregon
United States	Investigational Site Number 840506	Evansville	Indiana
United States	Investigational Site Number 840529	Indianapolis	Indiana
United States	Investigational Site Number 840514	Jacksonville	Florida
United States	Investigational Site Number 840539	Jupiter	Florida
United States	Investigational Site Number 840512	Las Vegas	Nevada
United States	Investigational Site Number 840516	Los Angeles	California
United States	Investigational Site Number 840510	Lyndhurst	Ohio
United States	Investigational Site Number 840532	Madisonville	Kentucky
United States	Investigational Site Number 840502	Miami	Florida
United States	Investigational Site Number 840528	Mission Viejo	California
United States	Investigational Site Number 840509	Newport Beach	California
United States	Investigational Site Number 840517	Norfolk	Virginia
United States	Investigational Site Number 840513	Olympia	Washington
United States	Investigational Site Number 840523	Palm Springs	California
United States	Investigational Site Number 840520	Pembroke Pines	Florida
United States	Investigational Site Number 840524	Ponte Vedra	Florida
United States	Investigational Site Number 840536	Port Orange	Florida
United States	Investigational Site Number 840508	Raleigh	North Carolina
United States	Investigational Site Number 840518	Richmond	Virginia
United States	Investigational Site Number 840538	Rochester	New York
United States	Investigational Site Number 840507	St. Petersburg	Florida
United States	Investigational Site Number 840522	Statesville	North Carolina
United States	Investigational Site Number 840525	Tempe	Arizona
United States	Investigational Site Number 840533	Tulsa	Oklahoma
United States	Investigational Site Number 840534	Westlake Village	California
United States	Investigational Site Number 840515	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (2)

Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, Du Y, Ferrand AC, Ginsberg HN, Stein EA. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg e — View Citation

McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving — View Citation

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 study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.	Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	Baseline to Week 12 (LOCF)	No
Secondary	Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis		Week 12 (LOCF)	No
Secondary	Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein 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.	Baseline to Week 12 (LOCF)	No
Secondary	Percent Change From Baseline in Fasting Triglycerides and 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 (inter-quartile range).	Baseline to Week 12 (LOCF)	No
Secondary	Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis	Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.	Baseline to Week 12 (LOCF)	No