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, Long-term 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>|
| 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 Fasting 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 Fasting Total Cholesterol (TC) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting Non 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) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting 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 24, 52: Treatment Period |  | Baseline, Week 24, 52 | 
| Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Percent Change From Baseline in Fasting 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 Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |  | Baseline, Week 12 | 
| Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 |  | Baseline, Week 12, 24, 52 | 
| Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) 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 (mg/dL) at Week 12, 24 and 52 |  | Week 12, 24, 52 | 
| Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 |  | Week 12, 24, 52 | 
| Plasma Concentration of PF-04950615 at Week 12, 24 and 52 | Plasma concentration of PF-04950615 at Week 12, 24 and 52 was reported. | 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. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, inflammation, mass, pain, paraesthesia, pruritus, swelling, vesicles, warmth, scab 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 Week 58 | 
| Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log2) unit was considered to be ADA positive and nAb titer >=1.58 (log2) unit was considered to be nAb positive. | Baseline up to Week 58 | 
| Number of Participants Who Changed Concomitant Medication During Extension Period | In this outcome measure, total number of participants who changed their lipid-lowering medications or added a monoclonal antibody medication during the extension period were reported. | Week 58 follow-up visit to Week 110 | 
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period |  | Baseline, Week 58 follow-up visit, 71, 84, 97, 110 | 
| Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log2) unit was considered to be ADA positive and nAb titer >=1.58 (log2) unit was considered to be nAb positive. | Week 58 follow-up visit, Week 71, Week 84, Week 97, Week 110 | 

 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, multiple cardiovascular disease risk factors