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

Study Overview
=================
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.

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 Familial Hypercholesterolemia

Conditions
-----------------
Heterozygous Familial Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: Bococizumab (PF-04950615;RN316)
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Treated with a statin. Fasting LDL-C > 70 mg/dL and triglyceride <=400 mg/dL. High or very high risk of incurring a cardiovascular event. Heterozygous familial hypercholesterolemia. Exclusion Criteria: Pregnant or breastfeeding females. Cardiovascular or cerebrovascular event of procedures during the past 30 days. Congestive heart failure NYHA class IV. Poorly controlled hypertension.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bococizumab (PF-04950615;RN316)<br>Bococizumab (PF-04950615;RN316) | Drug: Bococizumab (PF-04950615;RN316)<br>* 150 mg every 2 weeks, subcutaneous injection, 12 months<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* subcutaneous injection every 2 weeks for 12 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 |  | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Cholesterol (TC) at Week 12 |  | Baseline, Week 12 | 
| Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 |  | Baseline, Week 12 | 
| Percent Change From Baseline in Lipoprotein (a) at Week 12 |  | Baseline, Week 12 | 
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52 |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Total Cholesterol (TC) at Week 24 and 52 |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 24 and 52 |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 and 52 |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Lipoprotein (a) at Week 24 and 52 |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and 52 |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Triglycerides (TG) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Absolute Change From Baseline in Low Density Lipoprotein (LDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Total Cholesterol (TC) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Lipoprotein (a) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |  | 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 |  | 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 |  | 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 |  | 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 |  | Week 12, 24, 52 | 
| Plasma PF-04950615 Concentrations at Week 12, 24 and 52 |  | Week 12, 24, 52 | 
| Number of Participants With Adverse Events Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions | 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. | Baseline up to the end of study (up to 58 weeks) | 
| Percentage of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported in this outcome measure. ADA titer greater than or equal to (>=) 6.23 were considered as ADA positive and nAb titer level >=1.58 were considered as nAb positive. | Baseline up to the end of study (up to 58 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
High Risk of cardiovascular events, Heterozygous familial hypercholesterolemia