A Study of Alirocumab in Participants With Autosomal Dominant Hypercholesterolemia (ADH) and Gain-of-Function Mutations (GOFm) of the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) Gene or Loss-of-Function Mutations (LOFm) of the Apolipoprotein (Apo) B Gene

Browse trials for

• Hyperlipoproteinemia Type II 245
• Hypercholesterolemia 1,238

Hyperlipoproteinemia Type II

245 studies on the registry are indexed under Hyperlipoproteinemia Type II; 52 are open to participants now.

This study's enrollment of 23 is below the median of 86 across 170 interventional studies indexed under Hyperlipoproteinemia Type II.

Lead sponsor

Regeneron Pharmaceuticals is the lead sponsor of 400 studies on the registry; 91 are open to participants now.

Of its 120 completed or terminated interventional studies of FDA-regulated products, 77 (64%) have results posted.

Study arms

• Experimental
  GOFm PCSK9 (Cohort 1): Alirocumab From Day 1

  Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group A). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

  Drug: Alirocumab · Drug: Placebo

• Experimental
  GOFm PCSK9 (Cohort 1): Alirocumab From Day 15

  Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group B). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

  Drug: Alirocumab · Drug: Placebo

• Experimental
  GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1

  Participants with gain-of-function mutation (GOFm) in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in the apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group C). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

  Drug: Alirocumab · Drug: Placebo

• Experimental
  GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15

  Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group D). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

  Drug: Alirocumab · Drug: Placebo

Interventions

• DrugAlirocumab

  SC injection in the abdomen

  Also known as: Praluent®, REGN727, SAR236553

• DrugPlacebo

  SC injection in the abdomen

Primary outcomes

1. Percent Change in Measured Serum Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 15

   By day 15, participants in groups A and C had received 1 subcutaneous (SC) dose of 150 mg alirocumab and participants in group B and D had received 1 SC dose of placebo. \[Baseline adjusted least squares (LS) means and standard errors were obtained using analysis of covariance (ANCOVA) model specifying the treatment arm as the fixed effect and the baseline measured LDL-C value as a covariate.\]

   Time frame: Baseline to Day 15

Secondary outcomes

1. Percent Change in Apolipoprotein (Apo) B100 From Baseline to Day 15

   Baseline adjusted LS means and standard errors were obtained using the same ANCOVA model as for primary endpoint specifying the treatment arm as the fixed effect and the parameter value as a covariate.

   Time frame: Baseline to Day 15

2. Percent Change in Non High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 15

   Time frame: Baseline to Day 15

3. Percent Change in Total Cholesterol (Total-C) From Baseline to Day 15

   Time frame: Baseline to Day 15

4. Percent Change in Apolipoprotein (Apo) B100/ ApoA-1 Ratio From Baseline to Day 15

   Time frame: Baseline to Day 15

Baseline characteristics

2 further baseline measures are reported on the registry.

Publications

• Hopkins PN, Krempf M, Bruckert E, Donahue S, Yang F, Zhang Y, DiCioccio AT. Pharmacokinetic and pharmacodynamic assessment of alirocumab in patients with familial hypercholesterolemia associated with proprotein convertase subtilisin/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations. J Clin Lipidol. 2019 Nov-Dec;13(6):970-978. doi: 10.1016/j.jacl.2019.10.007. Epub 2019 Oct 21. PubMed 31767518 ↗
• Hopkins PN, Defesche J, Fouchier SW, Bruckert E, Luc G, Cariou B, Sjouke B, Leren TP, Harada-Shiba M, Mabuchi H, Rabes JP, Carrie A, van Heyningen C, Carreau V, Farnier M, Teoh YP, Bourbon M, Kawashiri MA, Nohara A, Soran H, Marais AD, Tada H, Abifadel M, Boileau C, Chanu B, Katsuda S, Kishimoto I, Lambert G, Makino H, Miyamoto Y, Pichelin M, Yagi K, Yamagishi M, Zair Y, Mellis S, Yancopoulos GD, Stahl N, Mendoza J, Du Y, Hamon S, Krempf M, Swergold GD. Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody. Circ Cardiovasc Genet. 2015 Dec;8(6):823-31. doi: 10.1161/CIRCGENETICS.115.001129. Epub 2015 Sep 15. PubMed 26374825 ↗