A Multiple Dose Study Of PF-04950615 (RN316) In Subjects On Maximum Doses Of Statins

Study Overview
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Brief Summary
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PF-04950615 is a new investigational hypercholesterolemic agent that is being tested in this study to evaluate if it can lower LDL cholesterol.

Official Title
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A Phase 2, Double-blind, Placebo-controlled, Randomized Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 Following Multiple Intravenous Doses In Hypercholesterolemic Subjects On Maximum Dose Of Atorvastatin Or Rosuvastatin.

Conditions
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Hypercholesterolemia, Dyslipidemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) of 18.5 to 40 kg/m2 On a stable maximum daily dose of a statin, defined as atorvastatin 80 mg or rosuvastatin 40 mg for a minimum of 45 days prior to Day 1. Lipids meet the following criteria twice during screening period: Fasting LDL C = or > 80 mg/dL; Fasting TG < 400 mg/dL. Exclusion Criteria: History of a cardiovascular or cerebrovascular event or procedure (eg, MI, stroke, TIA, angioplasty) during the past year. Poorly controlled type 1 or type 2 diabetes mellitus. Poorly controlled hypertension. Fasting triglycerides > 400 mg/dL 12 lead ECG demonstrating QTcFF >455 msec at screening.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment A<br> | Other: Placebo<br>* An infusion lasting approximately 60 minutes<br>|
| Experimental: Treatment B<br> | Drug: PF-04950615 (RN316)<br>* An infusion lasting approximately 60 minutes<br>|
| Experimental: Treatment C<br> | Drug: PF-04950615 (RN316)<br>* An infusion lasting approximately 60 minutes<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 Day 85 | Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration. | Baseline, Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than 70 and Less Than 100 Milligram Per Deciliter (mg/dL) |  | Day 29, 57, 85 | 
| Percentage of Participants Achieving at Least 30 Percent Decrease in Low-density Lipoprotein Cholesterol (LDL-C) |  | Day 29, 57, 85 | 
| Change From Baseline in Lipid Parameters at Day 29, 57 and 85 | Lipid parameters included: high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein-cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1). Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration. | Baseline, Day 29, 57, 85 | 
| Percent Change From Baseline in Lipid Parameters at Day 29, 57 and 85 | Lipid parameters included: high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-high-density lipoprotein-cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1). Baseline value was calculated as the average of Day 7 and Day 1 measurements collected prior to study drug administration. | Baseline, Day 29, 57, 85 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are events between first dose of study drug and up to Day 141 that were absent before treatment or that worsened relative to pretreatment state. Treatment related: a TEAE deemed related to the study drug by the investigator. TEAEs included SAEs (TESAEs) as well as non-serious AEs which occurred during the study. The participants with TEAEs, TESAEs and treatment-related TEAEs were reported. | Day 1 up to Day 141 | 
| Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Investigator assessed adverse events as mild (does not interfere with participant's usual function), moderate (interferes to some extent with participant's usual function) or severe (interferes significantly with participant's usual function). All causality TEAEs were assessed for severity. TEAEs are events between first dose of study drug and up to Day 141 that were absent before treatment or that worsened relative to pretreatment state. | Day 1 up to Day 141 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities | Criteria for clinically significant laboratory abnormalities were based on investigator's discretion. Total number of participants who met the criteria for any laboratory abnormal findings were reported. Laboratory parameters included: hematology, coagulation, liver function, renal function, electrolytes, hormones, chemistry and urinalysis. Screening was 21 days prior to start of study treatment. | Screening up to Day 141 | 
| Number of Participants With Clinically Significant Changes in Vital Signs and Electrocardiogram (ECG) Parameters | Number of participants with clinically significant changes in vital signs and ECG findings were reported. Criteria for clinical significant vital signs: maximum increase or decrease from baseline in supine systolic blood pressure (BP) greater than or equal to (>=) 30 millimeter of mercury (mmHg), maximum increase or decrease from baseline in supine diastolic BP of >=20 mmHg. Criteria for clinically significant ECG parameters: maximum increase of >=25 percent (%) for baseline value of greater than 200 millisecond (msec) or maximum increase of >=50% for baseline value of less than or equal to (<=) 200 msec for PR and QRS interval, maximum increase from baseline of greater than (>) 30 to <=60 msec and maximum increase from baseline of >60 msec for QT interval corrected using the Fridericia's formula (QTCF). Screening was 21 days prior to start of study treatment. | Screening up to Day 141 | 
| Number of Participants With Anti-drug (Anti-PF-04950615) Antibody (ADA) | Human serum samples of participants who received PF-04950615 (RN316) were analyzed for the presence of anti-PF-04950615 antibodies by using the semi quantitative enzyme-linked immunosorbent assay (ELISA). Results with titer value >=4.32 nanogram per milliliter of anti-PF-04950615 antibodies were counted as positive. Number of participants with presence of anti-PF-04950615 antibodies were reported in this outcome measure. | Day 1 up to Day 141 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolemia, dyslipidemia, high cholesterol, LDL, antibody, PCSK9, PF-04950615, RN316