Phase 3
Completed N=2,139
Randomized Clinical Trial of Bococizumab (PF-04950615; RN316) in Subjects With Hyperlipidemia or Mixed Dyslipidemia at Risk of Cardiovascular Events
Source: ClinicalTrials.gov NCT01968967 ↗Enrolled (actual)
2,139
Serious AEs
12.0%
Results posted
Jul 2017
Primary outcomePrimary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 — 1.0; -54.9 percent change — p=<0.001
◆ Published Evidence
Highly cited
366citations · ~41 / year
Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab.
Summary
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.
Linked Publications (5)
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Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab.
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Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: Results from the SPIRE randomized trials of bococizumab.
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Anti-drug Antibody Magnitude and Clinical Relevance Using Signal to Noise (S/N): Bococizumab Case Study.
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Genome-wide pharmacogenetics of anti-drug antibody response to bococizumab highlights key residues in HLA DRB1 and DQB1.
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Population PK/PD modeling of low-density lipoprotein cholesterol response in hypercholesterolemic participants following administration of bococizumab, a potent anti-PCSK9 monoclonal antibody.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 |
1.0; -54.9 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 |
-0.1; -34.9; 1.0; -30.5; -0.3; -25.3 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 |
0.4; -50.4; 1.5; -44.9; -0.4; -37.4 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 |
0.2; -49.7; 1.6; -43.8; -0.3; -36.8 | <0.001 sig |
| SECONDARY 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 |
1.9; -55.6; 3.9; -49.2; 3.2; -40.6 | <0.001 sig |
| SECONDARY 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 |
-1.5; -53.0; 1.1; -42.8; -1.2; -36.3 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 |
2.4; -26.3; 8.7; -22.7; 4.3; -20.9 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 |
0.4; 6.2; 0.5; 6.1; 1.2; 6.5 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period |
3.2; -47.5; 2.1; -39.5 | — |
| SECONDARY Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 |
3.5; -12.9; 5.1; -11.5; 0.3; -12.5 | — |
| SECONDARY Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 |
-0.6; 2.8; -0.9; 2.7; -1.2; 2.6 | — |
| SECONDARY Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 |
-1.2; -1.0; -0.9; 0.1; -2.5; -1.0 | — |
| SECONDARY Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 |
3.5; -12.9; 5.1; -11.5; 0.3; -12.5 | — |
| SECONDARY 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 |
109.1; 107.1; 0.3; -59.3 | — |
| SECONDARY 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 |
125.9; 121.5; -3.4; -64.8 | — |
| SECONDARY Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 |
113.5; 110.9; -0.7; -60.7 | — |
| SECONDARY Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 |
186.3; 183.1; -1.8; -64.5 | — |
| SECONDARY Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |
138.0; 135.3; -1.6; -67.0 | — |
| SECONDARY Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 |
94.0; 92.3; -0.7; -46.0 | — |
| SECONDARY Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12 |
45.3; 46.4; -0.0; -10.6 | — |
| SECONDARY Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 |
48.3; 47.8; -0.1; 2.5 | — |
| SECONDARY Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 |
4.1; 4.0; -0.0; -1.5; 0.0; -1.4 | — |
| SECONDARY Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 |
0.7; 0.7; 0.0; -0.3; 0.0; -0.3 | — |
| SECONDARY 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 |
45.3; 90.9; 43.2; 85.8; 45.0; 79.8 | — |
| SECONDARY 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 |
5.9; 78.6; 7.8; 69.8; 6.8; 61.4 | — |
| SECONDARY Plasma Concentration of PF-04950615 at Week 12, 24 and 52 |
4.91; 4.74; 3.60 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions |
2; 2; 56; 144 | — |
| SECONDARY Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period |
0.9; 46.7; 0.4; 30.3 | — |
| SECONDARY Number of Participants Who Changed Concomitant Medication During Extension Period |
2; 1; 2 | — |
| SECONDARY 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 |
-6.4; -10.4; -15.8; -20.8; -5.0 | — |
| SECONDARY Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period |
100.0; 36.8; 62.5; 31.3; 81.8; 45.5 | — |
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.
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.
Data sourced from ClinicalTrials.gov (NCT01968967) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.