Randomized Clinical Trial Of Bococizumab (PF-04950615; RN316) In Subjects With Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events

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

Official Title
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A Phase 3 Double-blind,Randomized, Placebo-controlled,Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events

Conditions
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Hyperlipidemia

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


Participation Criteria
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Eligibility Criteria
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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. 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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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> | Drug: Bococizumab (PF-04950615;RN316)<br>* 150 mg every 2 weeks, subcutaneous injection, 12 months<br>* Other names: RN316;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* subcutaneous injection, every 2 weeks for 12 months<br>|

What is the study measuring?
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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, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Non- High Density Lipoprotein-Cholesterol (Non HDL-C) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Primary Hyperlipidemia | Participants with primary hyperlipidemia are defined as participants with triglycerides (TG) level less than (<) 200 milligram per decilitre (mg/dL) (2.26 millimoles per litre [mmol/L]) at pre-randomization. | Baseline, Week 12 | 
| Percent Change From Baseline in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) at Week 12 in Participants With Mixed Dyslipidemia | Participants with mixed dyslipidemia are defined as TG level greater than or equal to (>=) 200 mg/dL (2.26 mmol/L) at pre-randomization. | Baseline, Week 12 | 
| Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 24 and 52 |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52 by Triglyceride Cut-off | Percent change from baseline in fasting LDL-C among participants with TG cut-off of <200 mg/dL and >=200 mg/dL (2.26 mmol/L) were reported in this outcome measure. | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Fasting Triglyceride (TG) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in ApolipoproteinA-I (ApoA-I) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in ApolipoproteinA-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 Fasting Low Density Lipoprotein-C (LDL-C) at Week 12 by Trigylceride Cut-Off | Absolute change from baseline among participants with TG cut-off of <200 mg/dL and >=200 mg/dL (2.26 mmol/L) were reported in this outcome measure. | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Absolute Change From Baseline in Total Cholesterol (TC) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Absolute Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Absolute Change From Baseline in Apolipoprotein B (ApoB) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Absolute Change From Baseline in Lipoprotein(a) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Absolute Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Absolute Change From Baseline in Ratio of Fasting 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 ApolipoproteinA-I (ApoB/ApoA-I Ratio) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percentage of Participants Achieving Fasting Low Density Lipoprotein-Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (2.59 Millimoles Per Litre) at Week 12, 24 and 52 |  | Week 12, 24 and 52 | 
| Percentage of Participants Achieving Fasting Low Density Lipoprotein-Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (1.81 Millimoles Per Litre) at Week 12, 24 and 52 |  | Week 12, 24 and 52 | 
| Plasma PF-04950615 Concentrations at Week 12, 24 and 52 |  | Week 12, 24, 52 | 
| Number of Participants With Adverse Events (AEs) 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's, polysynovitis, fever and if severe then included glomerulonephritis as well. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, pain, pruritus and rash. Participants with type 1 or type 3 hypersensitivity reactions and participants with injection site reactions were reported in this outcome measure. | Baseline up to the end of study (up to 58 weeks) | 
| Percentage of Participants With 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. Participants with their ADA titer >=6.23 were considered to be ADA positive and participants with their nAb titer >=1.58 were considered to be nAb positive. | Baseline up to the end of study (up to 58 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mixed dyslipidemia, high risk of cardiovascular events