Clinical Trial: An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of a RARγ-Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With The primary objective is to evaluate the ability of different doses of palovarotene to prevent HO at the flare-up site in subjects with FOP as assessed by plain radiographs.

This is a Phase 2, multi-center, randomized, double-blind, sponsor-unblinded, placebo-controlled study. Two cohorts of subjects will be randomized into different dosing regimens of palovarotene for a 6-week (42 days) treatment period. The study will consist of three periods:

  1. A Screening period to occur within 7 days of a distinct flare-up. The first dose of study drug will be taken within 7 days of the flare-up initiation.
  2. A double-blind treatment period of 6 weeks (42 days) duration.
  3. A follow-up period of 6 weeks (42 days) duration.

An initial cohort (Cohort 1) of subjects will be randomly assigned 3:1 to either palovarotene or placebo daily for 42 days. Subjects randomized to palovarotene in Cohort 1 will receive an initial daily dose of 10 mg for 14 days followed by 5 mg daily for 28 days.

In Cohort 2, new FOP subjects meeting all inclusion/exclusion criteria will be randomly assigned 3:3:2 to two dose regimens of palovarotene (10 mg for 14 days and 5 mg for 28 days; 5 mg for 14 days and 2.5 mg for 28 days) or placebo daily for 42 days. Doses will be weight-adjusted and subjects randomized within three weight-range categories (20 to <40 kg, 40 to <60 kg, and ≥60 kg).

Subjects completing the study and still meeting eligibility requirements will be given the opportunity to enroll into an open-label extension study.


Sponsor: Clementia Pharmaceuticals Inc.

Current Primary Outcome: Percentage of subject responders as assessed by plain radiographs. [ Time Frame: Study Day 42 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Numeric heterotopic ossification scores at the flare-up site as assessed by plain radiograph. [ Time Frame: Study Days 42 and 84 ]
  • Amount (area) of new heterotopic bone formed at the flare-up site assessed by plain radiographs. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Percentage of subject responders as assessed by plain radiographs. [ Time Frame: Study Day 84 ]
  • Plasma biomarker levels. [ Time Frame: Baseline, Study Days 14, 28, 42, and 84 ]
  • Amount of bone formation (volume) as assessed by low dose CT scan. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Presence of soft tissue swelling and/or cartilage as assessed by MRI (or soft tissue swelling by ultrasound in subjects unable to undergo MRI). [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Active range of motion measured by goniometer of the relevant joint. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Subject and Investigator global assessment of movement. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Pain and swelling at the flare-up site using a numeric rating scale for each symptom (or the Faces Pain Scale-Revised for subjects under 8 years of age). [ Time Frame: Baseline, Study Days 14, 28, 42, 63, and 84 ]
  • Use of assistive devices and adaptations for daily living by FOP subjects. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Duration of active, symptomatic flare-up. [ Time Frame: Symptom start date to symptom end date ]
  • Age-appropriate patient-reported assessment of physical function. [ Time Frame: Baseline, Study Days 14, 28, 42, 63, and 84 ]
  • Safety evaluation including adverse events, clinical safety laboratory parameters, and assessment of epiphyseal growth plate and linear growth in subjects under the age of 18 years. [ Time Frame: Study Days 1 (the first day of dosing), 14, 28, 42, 63, and 84 ]


Original Secondary Outcome:

  • Numeric heterotopic ossification scores at the flare-up site as assessed by plain radiograph. [ Time Frame: Study Days 42 and 84 ]
  • Amount (area) of new heterotopic bone formed at the flare-up site assessed by plain radiographs. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Percentage of subject responders as assessed by plain radiographs. [ Time Frame: Study Day 84 ]
  • Plasma biomarker levels. [ Time Frame: Baseline, Study Days 14, 28, 42, and 84 ]
  • Amount of bone formation (volume) as assessed by low dose CT scan. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Presence of soft tissue swelling and/or cartilage as assessed by MRI. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Active range of motion measured by goniometer of the relevant joint. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Pain and swelling at the flare-up site using a numeric rating scale for each symptom. [ Time Frame: Baseline, Study Days 14, 28, 42, 63, and 84 ]
  • Use of assistive devices and adaptations for daily living by FOP subjects. [ Time Frame: Baseline, Study Days 42 and 84 ]
  • Duration of active, symptomatic flare-up. [ Time Frame: Symptom start date to symptom end date ]
  • Patient-reported assessment of physical function. [ Time Frame: Baseline, Study Days 14, 28, 42, 63, and 84 ]
  • Safety evaluation including adverse events and clinical safety laboratory parameters. [ Time Frame: Study Days 1 (the first day of dosing), 14, 28, 42, 63, and 84 ]


Information By: Clementia Pharmaceuticals Inc.

Dates:
Date Received: July 13, 2014
Date Started: July 2014
Date Completion:
Last Updated: July 22, 2016
Last Verified: February 2016