Clinical Trial: A Trial of PF-06252616 in Ambulatory Participants With LGMD2I

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

Official Title: A Phase 1b/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Ambulatory Participants With

Brief Summary:

The investigational product PF 06252616, a humanized anti myostatin monoclonal antibody that neutralizes myostatin (GDF8) is in development for the treatment of Limb Girdle Muscular Dystrophy 2I (LGMD2I) to preserve and/or improve muscle function.

This study will provide the clinical assessment of the safety, tolerability, Pharmacokinetics and Pharmacodynamics of PF 06252616 following repeat IV doses in ambulatory adults with LGMD2I.


Detailed Summary: This study is a Phase 1b/2, open-label multiple ascending dose escalation study to evaluate the safety, tolerability, efficacy, PK and PD of PF 06252616 in ambulatory adults with LGMD2I. The study design is intended to determine the optimal safe and pharmacologically active dose of PF 06252616 in LGMD2I while providing an opportunity for all subjects to receive active drug for a rare and disabling disorder. The study will be conducted in three periods: Lead-In, Treatment and Follow-up periods. The Lead-In and Follow-up periods will each be 16 weeks to allow an assessment of the change of various outcome measures of this period of time and comparison of change in function before, during and after treatment. The Treatment period will be 32 weeks. Three cohorts of participants will be enrolled and receive escalating doses of PF 06252616. The first cohort will have the option to crossover to the highest dose.
Sponsor: Kathryn Wagner

Current Primary Outcome: Incidence of dose limiting or intolerability treatment related AEs [ Time Frame: Baseline through 96 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) of GDF-8 [ Time Frame: Baseline through 96 weeks ]
  • Area Under the Curve, steady state from Time Zero to end of dosing interval (AUCtau,ss) of GDF-8 [ Time Frame: Baseline through 96 weeks ]
  • Maximum Observed Serum Concentration at steady state (Cmax, ss) of GDF-8 [ Time Frame: Baseline through 96 weeks ]
  • Mean change from baseline in 10 meter walk/run time in seconds [ Time Frame: Baseline through 96 weeks ]
  • Mean change from baseline of Forced Vital Capacity in Liters [ Time Frame: Baseline through 96 weeks ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) of GDF-8 [ Time Frame: Baseline through 96 weeks ]
  • Observed Serum Trough Concentration at steady state (Ctrough,ss) of GDF-8 [ Time Frame: Baseline through 96 weeks ]
  • Observed Serum Concentration steady state average (Css,av) of GDF-8 [ Time Frame: Baseline through 96 weeks ]
  • Maximum Observed Serum Concentration (Cmax) of PF-06252616 [ Time Frame: Baseline through 96 weeks ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06252616 [ Time Frame: Baseline through 96 weeks ]
  • Minimum Observed Serum Trough Concentration (Ctrough) of PF-06252616 [ Time Frame: Baseline through 96 weeks ]
  • Serum Decay Half-Life (t1/2) of PF-06252616 [ Time Frame: Baseline through 96 weeks ]
  • Immunogenicity: Incidence of anti-drug antibody [ Time Frame: Baseline through 96 weeks ]
  • Immunogenicity: Incidence of neutralizing antibody [ Time Frame: Baseline through 96 weeks ]
  • Mean change from baseline in 2MWD in meters [ Time Frame: Baseline through 96 weeks ]
  • Mean change from baseline in TUG in seconds [ Time Frame: Baseline through 96 weeks ]
  • Mean change from baseline in muscle strength as measured by modified MRC scale [ Time Frame: Baseline through 96 weeks ]


Original Secondary Outcome: Same as current

Information By: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Dates:
Date Received: July 12, 2016
Date Started: July 2016
Date Completion:
Last Updated: July 19, 2016
Last Verified: July 2016