Clinical Trial: In-Home Evaluation of Episodic Administration of Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) Subjects

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Phase 2, In-Home, Safety and Efficacy Evaluation of Episodic Administration of Open-Label Palovarotene in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)

Brief Summary: Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation (heterotopic ossification or HO) in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. Mouse models of FOP have demonstrated the ability of retinoic acid receptor gamma (RARγ) agonists such as palovarotene to prevent HO following injury. This 36-month study will evaluate the long-term safety and efficacy of episodic treatment with palovarotene for flare-ups in FOP subjects who successfully complete two flare-up treatment periods (6 weeks duration) and two follow-up periods (6 weeks duration) in Study PVO-1A-202.

Detailed Summary:

The objectives of this Phase 2, open-label, multicenter, single-arm study are:

  • To evaluate the long-term safety and efficacy of prior palovarotene treatment over 36 months in FOP subjects who completed Study PVO-1A-202
  • To evaluate the safety and efficacy of palovarotene in FOP subjects experiencing new, distinct flare-ups during the 36-month follow-up period.

The follow-up portion of the study will consist of a Screening visit that will correspond to the last day (Study Day 84) of Study PVO-1A-202 and bi-annual assessments at Months 6, 12, 18, 24, 30, and 36.

Subjects experiencing a new, distinct flare-up during the 36-month follow-up will be evaluated and if eligible, receive palovarotene at the weight-adjusted equivalent of 10 mg for 14 days followed by 5 mg for at least 28 days. Any subject who received a lower dosing regimen due to tolerability issues during Study PVO-1A-202 will receive that tolerated dose.

For each flare-up there will be two periods:

  1. A Screening period to occur within 7 days of the start of a new, distinct flare-up. The first dose of palovarotene will be taken within 10 days of the flare-up onset to allow for shipment of study medication to the subject's home.
  2. A treatment period of at least 6 weeks duration. Subjects experiencing a new, distinct flare-up will be evaluated

Sponsor: Clementia Pharmaceuticals Inc.

Current Primary Outcome: Safety of palovarotene as assessed by the incidence of treatment-emergent adverse events (including those known to be associated with retinoids) and serious adverse events monitored throughout the treatment period. [ Time Frame: Treatment period (up to 36 months) ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Global assessment of movement by category as determined by a subject/proxy completed questionnaire [ Time Frame: Every 6 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  • Change from baseline in Cumulative Analogue Joint Involvement Scale (CAJIS) for FOP [ Time Frame: Study screening, every 6 months during follow-up; Flare-up screening and every 6 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  • Change from baseline in extent of heterotopic ossification by whole body low-dose computerized tomography (CT) scan [ Time Frame: Study screening and 36 months ]
  • Change from baseline in extent of heterotopic ossification by whole body dual-energy x-ray absorptiometry (DEXA) scan [ Time Frame: Study screening and 36 months ]
  • Change from baseline in pain at flare-up site using numeric rating scale (NRS) or Faces Pain Scale-Revised (FPS-R) [ Time Frame: Flare-up screening, every 2 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  • Change from baseline in swelling at flare-up site using numeric rating scale (NRS) [ Time Frame: Flare-up screening, every 2 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  • Change from baseline in physical function using the FOP-Physical Function Questionnaire (FOP-PFQ) [ Time Frame: Study screening, every 6 months during follow-up. Flare-up screening, every 6 weeks on study drug, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  • Change from baseline in physical and mental health using PROMIS Global Health Scale [ Time Frame: Study screening, every 6 months during follow-up. Flare-up screening, every 6 weeks on study drug, end of treatment (an expected average of 6 weeks), 6 weeks after end of treatment. ]
  • Duration of active, symptomatic flare-up as assessed by subject and Investigator [ Time Frame: Flare-up screening, after 6 weeks on study drug, every 2 weeks after week 6 until flare-up resolution ]
  • Use of assistive devices and adaptations for daily living [ Time Frame: Study screening, every 6 months during follow-up. Flare-up screening, 6 weeks after end of treatment (an expected average treatment of 6 weeks), and 6-month intervals for duration of study ]


Original Secondary Outcome: Same as current

Information By: Clementia Pharmaceuticals Inc.

Dates:
Date Received: August 6, 2015
Date Started: January 2016
Date Completion: December 2018
Last Updated: November 14, 2016
Last Verified: January 2016