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

• ClinicalTrials.gov Identifier: NCT01592240
• Recruitment Status: Completed
• First Posted: May 7, 2012
• Results First Posted: December 5, 2017
• Last Update Posted: December 5, 2017
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 3, 2012
• First Posted Date: May 7, 2012
• Results First Submitted Date: October 27, 2017
• Results First Posted Date: December 5, 2017
• Last Update Posted Date: December 5, 2017
• Actual Study Start Date: July 2012
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 27, 2017): Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline, Week 12 ]
• Original Primary Outcome Measures (submitted: May 4, 2012): The absolute change from baseline in Low Density Lipoprotein-cholesterol at the end of week 12 following randomization [ Time Frame: end of week 12 post randomization ]

Current Secondary Outcome Measures (submitted: October 27, 2017)

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

Original Secondary Outcome Measures (submitted: May 4, 2012)

• Low Density Lipoprotein-Cholesterol (LDL-C) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• Safety endpoints will include incidence of anti-drug antibody (ADA), injection site [ Time Frame: Month 6 ]
• Plasma steady-state PF-04950615 pharmacokinetic parameters what PK measurements are being done? [ Time Frame: Month 6 ]
• Proportion of subjects having LDL-C less than particular limits (<100mg/dL, <70 mg/dL, <40mg/L, <25mg/dL) [ Time Frame: Month 6 ]
• Total cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• Apolipoprotein B (ApoB) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• Apolipoprotein A1 (ApoA1), Apolipoprotein AII (ApoAII) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• Lipoprotein (a) (Lp(a)) will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• High Density Lipoprotein (HDL)-cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• Very Low Density Lipoprotein (VLDL)-cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• Triglycerides will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]
• non-HDL-cholesterol will be assessed as change and % change from baseline at the end of week 12 following randomization [ Time Frame: Week 12 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Monthly And Twice Monthly Subcutaneous Dosing Of PF-04950615 (RN316) In Hypercholesterolemic Subjects On A Statin
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypercholesterolemia

Intervention

• Drug: PBO
  Placebo Q28d
• Drug: 200mg PF-04950615 (RN316)
  PF-04950615 200 mg, Q28d
  Other Name: PF-04950615 (RN316)
• Drug: 300mg PF-04950615 (RN316)
  PF-04950615 300 mg, Q28d
  Other Name: PF-04950615 (RN316)
• Drug: PBO
  Placebo, Q14d
• Drug: PF-04950615
  PF-04950615 50mg, Q14d
  Other Name: PF-04950615 (RN316)
• Drug: PF-04950615
  PF-04950615 100 mg, Q14d
  Other Name: PF-04950615 (RN316)
• Drug: PF-04950615
  PF-04950615 150mg, Q14d
  Other Name: PF-04950615 (RN316)

Study Arms

• 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.
  Interventions:

  • Drug: PBO
  • Drug: 200mg PF-04950615 (RN316)
  • Drug: 300mg PF-04950615 (RN316)
• 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.
  Interventions:

  • Drug: PBO
  • Drug: PF-04950615
  • Drug: PF-04950615
  • Drug: PF-04950615

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 27, 2017): 354
• Original Estimated Enrollment (submitted: May 4, 2012): 350
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01592240
• Other Study ID Numbers: B1481015; 2012-001226-10 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: October 2017