Clinical Trial: A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 2 Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study To Evaluate The Safety, Efficacy, Pharmacokinetics And Pharmacodynamics Of Pf-06252616 In Ambulatory Boys With Duc

Brief Summary: This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Three intravenous (IV) dose levels will be investigated in a within subject dose escalating fashion. Subjects will be randomly assigned to 1 of 3 sequence groups for approximately 96 weeks (2 periods of 48 weeks each). In period 1, two of the sequence groups will receive PF-06252616 and one sequence group will receive placebo. In period 2, the placebo group will switch to PF-06252616 and the two remaining sequence groups will either receive placebo or PF-06252616. Efficacy will be based on an observed mean change from baseline on function (4 stair climb) of PF-06252616 as compared to the placebo at the end of period 1. Period 2 provides an opportunity to evaluate PK. Subjects will receive monthly IV infused doses of either PF-06252616 or placebo and will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional evaluations (pulmonary function testing, 4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing and the six minute walk test), pharmacokinetic testing and pharmacodynamic testing to evaluate changes in muscle volume (MRI).

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome:

  • Incidence of dose limiting or intolerability treatment related AEs [ Time Frame: Baseline through 49 Weeks ]
  • Mean change from baseline on the 4 Stair Climb (4SC) as compared to placebo in seconds [ Time Frame: Baseline, 49 Weeks ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean change from baseline as compared to placebo of Forced Vital Capacity in liters [ Time Frame: Baseline, 17, 33 and 49 Weeks ]
  • Mean change from baseline as compared to placebo in the NSAA score [ Time Frame: Baseline, 17, 33 and 49 Weeks ]
  • Mean change from baseline as compared to placebo in the ankle range of motion in degrees [ Time Frame: Baseline, 17, 33 and 49 Weeks ]
  • Mean change from baseline as compared to placebo in the PUL score [ Time Frame: Baseline, 17, 33 and 49 Weeks ]
  • Mean change from baseline as compared to placebo in the 6MWD in meters [ Time Frame: Baseline, 17, 33 and 49 Weeks ]
  • Mean change from baseline as compared to placebo muscle strength as measured by hand held myometry in kilograms [ Time Frame: Baseline, 17, 33 and 49 Weeks ]
  • Mean change from baseline as compared to placebo in the thigh muscle volume by MRI in mm3 [ Time Frame: Baseline, 17, 33 and 49 Weeks ]
  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Area Under the Curve, steady state from Time Zero to end of dosing interval (AUCtau,ss) of GDF-8 [ Time Frame: Baseline through Week 93 ]
  • Concentration at time 0 (pre-dose), C(0) of GDF-8 [ Time Frame: Baseline ]
  • Maximum Observed Serum Concentration at steady state (Cmax, ss) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Observed Serum Trough Concentration at steady state (Ctrough,ss) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Observed Serum Concentration steady state average (Css,av) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Maximum Observed Serum Concentration (Cmax) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Minimum Observed Serum Trough Concentration (Ctrough) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Serum Decay Half-Life (t1/2) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Area Under the Curve From Time Zero to Last Quantifiable Serum Concentration (AUCt) of PF-06252616 [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Average Observed Serum Concentration (Cav) of PF-06252616) [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Clearance (CL) of PF-06252616 [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Volume of Distribution at Steady State (Vss) of PF-06252616 [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Immunogenicity: Incidence of anti-drug antibody [ Time Frame: Baseline through 97 Weeks ]
  • Immunogenicity: Incidence of neutralizing antibody [ Time Frame: Baseline through 97 Weeks ]
  • Within subject change from baseline in thigh mucscle volume mm3 [ Time Frame: 97 Weeks ]


Original Secondary Outcome:

  • Mean change from baseline as compared to placebo of Forced Vital Capacity in liters [ Time Frame: Baseline, 17, 33, 49, 65, 81 and 97 Weeks ]
  • Mean change from baseline as compared to placebo in the NSAA score [ Time Frame: Baseline, 17, 33, 49, 65, 81, 97 Weeks ]
  • Mean change from baseline as compared to placebo in the ankle range of motion in degrees [ Time Frame: Baseline, 17, 33, 49, 65, 81 and 97 Weeks ]
  • Mean change from baseline as compared to placebo in the PUL score [ Time Frame: Baseline, 17, 33, 49, 65, 81 and 97 Weeks ]
  • Mean change from baseline as compared to placebo in the 6MWD in meters [ Time Frame: Baseline, 17, 33, 49, 65, 81 and 97 Weeks ]
  • Mean change from baseline as compared to placebo muscle strength as measured by hand held myometry in kilograms [ Time Frame: Baseline, 17, 33, 49, 65, 81 and 97 Weeks ]
  • Mean change from baseline as compared to placebo in muscle strength as measure by the modified MRC scale [ Time Frame: Baseline, 17, 33, 49, 65, 81 and 97 Weeks ]
  • Mean change from baseline as compared to placebo in the thigh muscle volume by MRI in mm3 [ Time Frame: Baseline, 17, 33, 49, 65, 81 and 97 Weeks ]
  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Area Under the Curve, steady state from Time Zero to end of dosing interval (AUCtau,ss) of GDF-8 [ Time Frame: Baseline through Week 93 ]
  • Concentration at time 0 (pre-dose), C(0) of GDF-8 [ Time Frame: Baseline ]
  • Maximum Observed Serum Concentration at steady state (Cmax, ss) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Observed Serum Trough Concentration at steady state (Ctrough,ss) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Observed Serum Concentration steady state average (Css,av) of GDF-8 [ Time Frame: Baseline through 93 Weeks ]
  • Maximum Observed Serum Concentration (Cmax) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Minimum Observed Serum Trough Concentration (Ctrough) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Serum Decay Half-Life (t1/2) of PF-06252616 [ Time Frame: Baseline through 93 Weeks ]
  • Area Under the Curve From Time Zero to Last Quantifiable Serum Concentration (AUCt) of PF-06252616 [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Average Observed Serum Concentration (Cav) of PF-06252616) [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Clearance (CL) of PF-06252616 [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Volume of Distribution at Steady State (Vss) of PF-06252616 [ Time Frame: Baseline, 1, 13, 17, 29, 33 and 45 Weeks ]
  • Immunogenicity: Incidence of anti-drug antibody [ Time Frame: Baseline through 97 Weeks ]
  • Immunogenicity: Incidence of neutralizing antibody [ Time Frame: Baseline through 97 Weeks ]


Information By: Pfizer

Dates:
Date Received: November 4, 2014
Date Started: November 24, 2014
Date Completion: May 24, 2019
Last Updated: May 2, 2017
Last Verified: May 2017