An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)
Condition: Fibrodysplasia Ossificans Progressiva
MeSH terms: Myositis Ossificans
Study type: Interventional
Phase: Phase 2

Summary: 
      Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease
      characterized by heterotopic ossification (HO), i.e., abnormal bone formation, often
      associated with painful, recurrent episodes of soft tissue swelling (flare-ups). Lesions
      begin in early childhood and lead to progressive ankyloses of major joints with resultant
      loss of movement.

      In this study, the ability of different palovarotene dosing regimens to prevent the formation
      of new HO will be evaluated in adult and pediatric participants with FOP.
    

Detailed description: 
      The main objective of this Phase 2, multicenter, open-label study is to evaluate the safety
      and efficacy of different palovarotene dosing regimens in participants with FOP. Efficacy
      will be assessed based on the ability of palovarotene to prevent the formation of new
      heterotopic ossification (HO) as assessed by low-dose whole body computed tomography (WBCT)
      scan, excluding head.

      The study was divided into four parts: Part A (completed on July 2017), Part B (completed on
      October 2018), Part C (completed) and Part D (completd). Each part was associated with
      revised palovarotene treatment regimens.

      In Part A, all pediatric and adult participants who successfully completed Study PVO-1A-201
      were enrolled and followed for up to 36 months. Participants who had an eligible flare-up
      received 10 mg palovarotene daily for 14 days, followed by 5 mg palovarotene daily for 28
      days (or weight-based equivalent).

      In Part B, participants who successfully completed Study PVO-1A-201 (including any
      participant who participated in Part A of Study PVO-1A-202) as well as up to 20 new adult
      participants were followed for up to 24 months. The Adult Cohort included all participants
      with at least 90% skeletal maturity, regardless of age. The Pediatric Cohort included all
      participants with less than 90% skeletal maturity. Any Pediatric Cohort participant who
      achieved ≥90% skeletal maturity during Part B was considered for enrollment into the Adult
      Cohort at the discretion of the Investigator. Part B added a 5 mg palovarotene daily chronic
      treatment regimen administered between flare-ups for participants in the Adult Cohort for up
      to 24 months. Part B also increased the flare-up dosing to 20 mg palovarotene daily for 28
      days, followed by 10 mg palovarotene daily for 56 days (or weight-adjusted equivalents in the
      Pediatric Cohort). Treatment could be extended if the flare-up was still ongoing.

      In Part C, participants from Part B are being followed for up to an additional 48 months.
      There will be no new participants in Part C. All eligible participants, including skeletally
      immature participants, are receiving 5 mg palovarotene daily chronic treatment regimen
      (weight-adjusted doses for skeletally immature participants).

      In Part D, annual post last dose of study treatment assessments for up to 2 years will be
      obtained in participants who were skeletally immature at the time of study treatment
      discontinuation in order to obtain longer-term safety data. No new participants will be
      enrolled into Part D.

      Part C plus Part D duration will not exceed 48 months.

      All participants will undergo all study procedures as specified in the respective schedule of
      assessments and for as long as they are not 100% skeletally mature.
    

Intervention name(s): Palovarotene dose level 1; Palovarotene dose level 2; Palovarotene dose level 3; Palovarotene dose level 4
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Palovarotene was taken orally once daily at approximately the same time each day.; Palovarotene will be taken orally once daily at approximately the same time each day.; Palovarotene will be taken orally once daily at approximately the same time each day.; Palovarotene will be taken orally once daily at approximately the same time each day.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Open-label extension study; Clinical trial Phase 2; Efficacy and safety; Heterotopic ossification; Fibrodysplasia Ossificans Progressiva; Flare-up; Palovarotene; Retinoic acid receptor agonist; Retinoic acid receptor gamma agonist; Clementia; Myositis Ossificans Progressiva; Munchmeyer's Disease; FOP; Ipsen