Clinical Trial: A 52 Week Study To Assess The Use Of Bococizumab (PF-04950615; RN316) In Subjects With Heterozygous Familial Hypercholesterolemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A 52 Week, Phase 3 Double-blind, Randomized, Placebo-controlled, Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Heterozygous

Brief Summary: This is a multicenter, randomized study in subjects with heterozygous familial hypercholesterolemia receiving highly effective statins to assess the safety, efficacy and tolerability of Bococizumab (PF-04950615; RN316) to lower LDL-C.

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]

Original Primary Outcome: Percent Change from Baseline in LDL-C at Week 12 [ Time Frame: 12 weeks ]

Current Secondary Outcome:

• Percent Change From Baseline in Total Cholesterol (TC) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52 [ Time Frame: Baseline, Week 24, 52 ]
• Percent Change From Baseline in Total Cholesterol (TC) at Week 24 and 52 [ Time Frame: Baseline, Week 24, 52 ]
• Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 24 and 52 [ Time Frame: Baseline, Week 24, 52 ]
• Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 and 52 [ Time Frame: Baseline, Week 24, 52 ]
• Percent Change From Baseline in Lipoprotein (a) at Week 24 and 52 [ Time Frame: Baseline, Week 24, 52 ]
• Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and 52 [ Time Frame: Baseline, Week 24, 52 ]
• Percent Change From Baseline in Triglycerides (TG) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Low Density Lipoprotein (LDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Absolute Change From Baseline in Total Cholesterol (TC) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Absolute Change From Baseline in Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Absolute Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Absolute Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Absolute Change From Baseline in Ratio of Total Cholesterol to High Density Lipoprotein Cholesterol (TC/HDL-C Ratio) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Absolute Change From Baseline in Ratio of Apolipoprotein B to Apolipoprotein A-I (ApoB/ApoA-I Ratio) at Week 12, 24 and 52 [ Time Frame: Baseline, Week 12, 24, 52 ]
• Percentage of Participants Achieving Low Density Lipoprotein Cholesterol (LDL-C) Level Less Than or Equal to (<=) 100 Milligram Per Deciliter (2.59 Millimoles Per Liter) at Week 12, 24 and 52 [ Time Frame: Week 12, 24, 52 ]
• Percentage of Participants Achieving Low Density Lipoprotein Cholesterol (LDL-C) Level Less Than or Equal to (<=) 70 Milligram Per Deciliter (1.81 Millimoles Per Liter) at Week 12, 24 and 52 [ Time Frame: Week 12, 24, 52 ]
• Plasma PF-04950615 Concentrations at Week 12, 24 and 52 [ Time Frame: Week 12, 24, 52 ]
• Number of Participants With Adverse Events Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions [ Time Frame: Baseline up to the end of study (up to 58 weeks) ]
  Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia, polysynovitis, fever and if severe then included glomerulonephritis as well. Injection site reaction is a reaction at the site of the subcutaneous injection and characterized by the symptoms of erythema, swelling, tenderness and warmth. Participants with any of the above type 1 or type 3 hypersensitivity reactions and participants with any of the above injection site reactions were reported in this outcome measure.
• Percentage of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibod
  
  

  Original Secondary Outcome:

  • Change from Baseline in Lipid Parameters at Week 12 [ Time Frame: 12 weeks ]
    Mean Total Cholesterol (TC), Apolipoprotein B (ApoB), non- HDL-C, lipoprotein (a), High Density Lipoprotein (HDL), Apolipoprotein A-I (ApoA-I), Apoliprotein A-II (ApoA-II), Triglycerides, TC/HDL and ApoB/ApoA-I ratio.
  • Change from Baseline in Lipid Parameters at Week 24 [ Time Frame: 24 weeks ]
    Low Density Lipoprotein (LDL), Mean Total Cholesterol (TC), Apolipoprotein B (ApoB), non- HDL-C, lipoprotein (a), High Density Lipoprotein (HDL), Apolipoprotein A-I (ApoA-I), Apoliprotein A-II (ApoA-II), Triglycerides, TC/HDL and ApoB/ApoA-I ratio.
  • Change from Baseline in Lipid Parameters at Week 52 [ Time Frame: 52 weeks ]
    Low Density Lipoprotein (LDL), Mean Total Cholesterol (TC), Apolipoprotein B (ApoB), non- HDL-C, lipoprotein (a), High Density Lipoprotein (HDL), Apolipoprotein A-I (ApoA-I), Apoliprotein A-II (ApoA-II), Triglycerides, TC/HDL and ApoB/ApoA-I ratio.
  • Proportion of Subjects Achieving Fasting LDLC <= 100 mg/dL and <=70 mg/dL [ Time Frame: 12 weeks ]
    Proportion of Subjects Achieving Fasting LDLC <= 100 mg/dL and <=70 mg/dL
  • Proportion of Subjects Achieving Fasting LDLC <= 100 mg/dL and <=70 mg/dL [ Time Frame: 24 weeks ]
    Proportion of Subjects Achieving Fasting LDLC <= 100 mg/dL and <=70 mg/dL
  • Proportion of Subjects Achieving Fasting LDLC <= 100 mg/dL and <=70 mg/dL [ Time Frame: 52 weeks ]
    Proportion of Subjects Achieving Fasting LDLC <= 100 mg/dL and <=70 mg/dL
  • Plasma PF-04950615 concentration [ Time Frame: 12 weeks ]
    Plasma PF-04950615 concentration
  • Plasma PF-04950615 concentration [ Time Frame: 24 weeks ]
    Plasma PF-04950615 concentration
  • Plasma PF-04950615 concentration [ Time Frame: 52 weeks ]
    Plasma PF-04950615 concentration
  
  
  Information By: Pfizer
  

  Dates:
  Date Received: October 21, 2013
  Date Started: October 2013
  Date Completion:
  Last Updated: April 7, 2017
  Last Verified: March 2017