Monthly And Twice Monthly Subcutaneous Dosing Of PF-04950615 (RN316) In Hypercholesterolemic Subjects On A Statin

A Phase 2b Double-blind, Randomized, Placebo-controlled, Parallel Group, Dose-ranging Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 Following Monthly And Twice Monthly Subcutaneous Dosing For Six Months In Hypercholesterolemic Subjects On A Statin

To evaluate the Low Density Lipoprotein-Cholesterol (LDL-C) lowering effect of PF-04950615 administered subcutaneously at monthly intervals, or twice monthly intervals in subjects with high cholesterol whose LDL-cholesterol is >/=80 mg/dL on background treatment with a statin.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: PBO; Drug: 200mg PF-04950615 (RN316); Drug: 300mg PF-04950615 (RN316); Drug: PBO; Drug: PF-04950615; Drug: PF-04950615; Drug: PF-04950615

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliated Research Center, Inc.
    • Huntsville, Alabama, United States, 35801
      • The Office of James G. McMurray, MD
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Southwest Heart Group
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Aureus Research Inc.
  • California
    • Dinuba, California, United States, 93618
      • Universal Biopharma Research Institute Inc. - Alta Family Health Clinic
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Norwalk, California, United States, 90650
      • The Office of Lucita M. Cruz, MD, Inc.
    • Santa Rosa, California, United States, 95405
      • Radiant Research
    • Stockton, California, United States, 95204
      • St. Joseph's Medical Associates
    • Tustin, California, United States, 92780
      • Orange County Research Center
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Zasa Clinical Research
    • Davie, Florida, United States, 33312
      • Florida Health Center
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Gainesville, Florida, United States, 32605
      • Florida Research Network, LLC
    • Hialeah, Florida, United States, 33010
      • In Vivo Clinical Research, Inc.
    • Hialeah, Florida, United States, 33012
      • Health Care Family Rehab and Research Center
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33155
      • Community Research Foundation, Inc.
    • Miami, Florida, United States, 33185
      • Kendall South Medical Center, Inc.
    • Orlando, Florida, United States, 32804
      • Omega Research Consultants, LLC
    • Pinellas Park, Florida, United States, 33782
      • DMI Research
    • Ponte Vedra, Florida, United States, 32081
      • St Johns Center For Clinical Research
    • Seminole, Florida, United States, 33774
      • The Office of Bridget Bellingar, DO
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
    • Atlanta, Georgia, United States, 30328
      • Radiant Research, Inc.
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Fox Valley Clinical Research Center, LLC
    • Chicago, Illinois, United States, 60654
      • Radiant Research, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Midwest Heart & Vascular Specialists
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Clinical Research Center
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
    • Lewiston, Maine, United States, 04240
      • Maine Research Associates
  • Massachusetts
    • Haverhill, Massachusetts, United States, 01830
      • ActivMed Practices and Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Radiant Research, Inc.
  • Missouri
    • Kansas City, Missouri, United States, 64106
      • Dybedal Clinical Research Center
  • Montana
    • Missoula, Montana, United States, 59808
      • Montana Medical Research, Inc.
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Clinical Research and Osteoporosis Center, Inc.
  • New York
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Clinical Trials of America, Inc.
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury
    • Winston-Salem, North Carolina, United States, 27103
      • Clinical Trials of America, Inc.
    • Winston-Salem, North Carolina, United States, 27103
      • Ardmore Family Practice
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Sentral Clinical Research Services
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Group, Ltd.
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd.
    • Mason, Ohio, United States, 45040
      • Albert J. Weisbrot, M.D., Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Lynn Institute of Norman
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Upstate Pharmaceutical Research
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
  • Texas
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Center for Cardiovascular Disease Prevention
    • Hurst, Texas, United States, 76054
      • Protenium Clinical Research, LLC
    • San Antonio, Texas, United States, 78229
      • Innovative Clinical Trials
    • San Antonio, Texas, United States, 78205
      • Paragon Research Center, LLC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research- Norfolk, Inc
    • Richmond, Virginia, United States, 23294
      • National Clinical Research - Richmond, Inc.
  • Washington
    • Spokane, Washington, United States, 99204
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects should be receiving a stable dose (at least 6 weeks) of any statin and continue on same dose of statin for the duration of this trial.
• Lipids should meet the following criteria on a background treatment with a statin at 2 screening visits that occur at screening and at least 7 days prior to randomization on Day 1:
• Fasting LDL-C greater than or equal to 80 mg/dL (2.31 mmol/L);
• Fasting TG less than or equal to 400 mg/dL (4.52 mmol/L).
• Subject's fasting LDL-cholesterol must greater than or equal to 80 mg/dL (2.31 mmol/L at the initial screening visit, and the value at the second visit within 7 days of randomization must be not lower than 20% of this initial value to meet eligibility criterion for this trial.

Exclusion Criteria:

• Participation in other studies within 3 months before the current study begins and/or during study participation.
• Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 63 days after last dose of investigational product.
• History of a cardiovascular or cerebrovascular event or procedure (eg, MI, stroke, TIA, angioplasty) during the past 6 months. Congestive heart failure (CHF), NYHA functional classes III or IV.
• Poorly controlled type 1 or type 2 diabetes mellitus (defined as HbA1c >9%).
• Poorly controlled hypertension.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Q28d Dosing Arm; A total of 7 dose groups in two dosing schedules, 50 subjects per dose group are planned. Q28d dose group will receive subcutaneous administration of PF-04950615 or Placebo once a month.	Drug: PBO; Placebo Q28d; Drug: 200mg PF-04950615 (RN316); PF-04950615 200 mg, Q28d; Other Names: PF-04950615 (RN316); Drug: 300mg PF-04950615 (RN316); PF-04950615 300 mg, Q28d; Other Names: PF-04950615 (RN316); Drug: PBO; Placebo, Q14d
EXPERIMENTAL: Q14d Dosing Arm; A total of 7 dose groups in two dosing schedules, 50 subjects per dose group are planned. Q14d dose group will receive subcutaneous administration of PF-04950615 or Placebo every 2 weeks.	Drug: PBO; Placebo Q28d; Drug: PBO; Placebo, Q14d; Drug: PF-04950615; PF-04950615 50mg, Q14d; Other Names: PF-04950615 (RN316); Drug: PF-04950615; PF-04950615 100 mg, Q14d; Other Names: PF-04950615 (RN316); Drug: PF-04950615; PF-04950615 150mg, Q14d; Other Names: PF-04950615 (RN316)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 24		Baseline, Week 24
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Apolipoprotein B (ApoB) at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Apolipoprotein A1 (ApoA1) at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Apolipoprotein A1 (ApoA1) at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Apolipoprotein AII (ApoAII) at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Apolipoprotein AII (ApoAII) at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Total Cholesterol at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Total Cholesterol at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Lipoprotein (a) (Lp [a]) at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Lipoprotein (a) (Lp [a]) at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Triglycerides at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Triglycerides at Week 12 and 24		Baseline, Week 12, 24
Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 12 and 24		Baseline, Week 12, 24
Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 12 and 24		Baseline, Week 12, 24
Percentage of Participants With Positive Anti-drug (Anti-PF-04950615) Antibodies (ADA)	Participants with titer value greater than or equal to 4.32 nanogram per milliliter were considered positive.	Baseline up to Day 211 for every 28 days groups and Baseline up to Day 225 for every 14 days groups
Percentage of Participants With Injection Site Adverse Events	Injection site adverse events included injection site bruising, discomfort, erythema, hemorrhage, induration, inflammation, pain, paresthesia, pruritus, swelling, urticaria, reaction and rash.	Baseline up to Day 211 for 28 days groups and Baseline up to Day 225 for 14 days groups
Plasma Concentration of PF-04950615 at Week 12 and 24		Week 12, 24
Percentage of Participants With Low Density Lipoprotein-cholesterol Less Than (<) 100, <70, <40 and <25 Milligram Per Deciliter (mg/dL)		Week 12, 24

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Ballantyne CM, Neutel J, Cropp A, Duggan W, Wang EQ, Plowchalk D, Sweeney K, Kaila N, Vincent J, Bays H. Results of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, from a randomized, placebo-controlled, dose-ranging study in statin-treated subjects with hypercholesterolemia. Am J Cardiol. 2015 May 1;115(9):1212-21. doi: 10.1016/j.amjcard.2015.02.006. Epub 2015 Feb 12.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2012
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): May 1, 2013

Study Registration Dates

• First Submitted: May 3, 2012
• First Submitted That Met QC Criteria: May 4, 2012
• First Posted (ESTIMATE): May 7, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 5, 2017
• Last Update Submitted That Met QC Criteria: October 27, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: PF-04950615; RN316
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Bococizumab
• Other Study ID Numbers: B1481015; 2012-001226-10 (EUDRACT_NUMBER)