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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02190747
• Date of registration: 13/07/2014
• Prospective Registration: No
• Primary sponsor: Clementia Pharmaceuticals Inc.
• Public title: An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects
• Scientific title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of a RAR?-Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
• Date of first enrolment: July 2014
• Target sample size: 40
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02190747
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

France, United Kingdom, United States

Contacts

• Name: Ipsen Medical Director
• Affiliation: Ipsen

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written, signed, and dated informed subject/parent consent or age-appropriate assent.

- Subjects clinically diagnosed with classic Fibrodysplasia Ossificans Progressiva
(FOP).

- Symptomatic onset of a distinct flare-up within 7 days of Study Day 1 (start of study
drug) and defined by the presence of at least two of six of the following symptoms:
pain, soft tissue swelling, decreased range of motion, stiffness, redness, and warmth.
Flare-up must be confirmed by the physician at the Screening visit.

- Flare-up is at an appendicular area (upper or lower extremity), abdomen, or chest; and
subject has received, is receiving, or is willing to receive treatment per standard of
care, which may or may not include oral prednisone (2 mg/kg PO to a maximum dose of
100 mg daily) for 4 days.

- Abstinent or using two highly effective forms of birth control.

- Subjects must be accessible for treatment and follow-up. Subjects living at distant
locations from the investigational site must be able and willing to travel to a site
for the initial and all follow-up visits.

Exclusion Criteria:

- Weight <20 kg.

- Intercurrent non-healed fracture at any location.

- Complete immobilization of joint at site of flare-up.

- The inability of the subject to undergo imaging assessments using plain radiographs.

- If currently using vitamin A or beta carotene, multivitamins containing vitamin A or
beta carotene, or herbal preparations, fish oil, and unable or unwilling to
discontinue use of these products for the duration of the study.

- Exposure to synthetic oral retinoids in the past 30 days prior to Screening (signature
of the informed consent).

- Concurrent treatment with tetracycline due to the potential increased risk of
pseudotumor cerebri.

- History of allergy or hypersensitivity to retinoids or lactose.

- Concomitant medications that are inhibitors or inducers of CYP450 3A4 activity.

- Amylase or lipase >1.5x above the upper limit of normal or with a history of chronic
pancreatitis.

- Elevated aspartate aminotransferase or alanine aminotransferase >2.5x the upper limit
of normal.

- Fasting triglycerides >400 mg/dL with or without therapy.



Age minimum: 6 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Fibrodysplasia Ossificans Progressiva

Intervention(s)

Drug: Placebo

Drug: Palovarotene

Primary Outcome(s)

Percentage of Responders at Week 6 [Time Frame: Baseline (Day 1) and Week 6 (Day 42)]

Secondary Outcome(s)

Change From Baseline in Amount (Area) of New HO Formed at the Flare-up Site at Weeks 6 and 12 [Time Frame: Baseline, Weeks 6 and 12]

Change From Baseline in C-Terminal Telopeptide at Weeks 2, 4, 6 and 12 [Time Frame: Baseline, Weeks 2, 4, 6 and 12]

Duration of Active Symptomatic Flare-up [Time Frame: From Day 1 to Day 84]

Percentage of Responders at Week 12 [Time Frame: Baseline and Week 12]

Percentage of Subjects Who Used Any Assistive Devices and Adaptations for Daily Living at Weeks 6 and 12 [Time Frame: Weeks 6 and 12]

Change From Baseline in Amount of Bone Formation (Volume) at Weeks 6 and 12 [Time Frame: Baseline, Weeks 6 and 12]

Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 [Time Frame: Baseline, Weeks 2, 4, 6, 9 and 12]

Apparent Terminal Elimination Half-life (t1/2) of Palovarotene [Time Frame: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6]

Maximum Measured Plasma Concentration (Cmax) of Palovarotene [Time Frame: Pre-dose and 3, 6, 10, and 24 hours (hrs) post-dose at Week 2, and at Week 4 or 6]

Percentage of Subjects With Soft Tissue Swelling and Cartilage Formation Assessed by Magnetic Resonance Imaging (MRI) or Ultrasound (US) at Weeks 6 and 12 [Time Frame: Weeks 6 and 12]

Change From Baseline in Procollagen Type 1 N-Terminal Propeptide at Weeks 2, 4, 6 and 12 [Time Frame: Baseline, Weeks 2, 4, 6 and 12]

Change From Baseline in C-Reactive Protein at Weeks 2, 4, 6 and 12 [Time Frame: Baseline, Weeks 2, 4, 6 and 12]

Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 [Time Frame: Baseline, Weeks 2, 4, 6, 9 and 12]

Minimum Measured Plasma Concentration (Cmin) of Palovarotene [Time Frame: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6]

Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 [Time Frame: Weeks 6 and 12]

Area Under the Plasma Concentration Versus Time Curve Over the 24-hr Dosing Interval (AUC[0-24hr]) of Palovarotene [Time Frame: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6]

Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12 [Time Frame: Baseline, Weeks 2, 4, 6, 9 and 12]

Change From Baseline in Procollagen Type 1 C-Terminal Propeptide Biomarker at Weeks 2, 4, 6 and 12 [Time Frame: Baseline, Weeks 2, 4, 6 and 12]

Apparent Clearance of Palovarotene (CL/F) [Time Frame: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6]

Time of Maximum Measured Plasma Concentration (Tmax) of Palovarotene [Time Frame: Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6]

Change From Baseline in Bone Specific Alkaline Phosphatase at Weeks 2, 4, 6 and 12 [Time Frame: Baseline, Weeks 2, 4, 6 and 12]

Change From Baseline in Percent of Normal Arc of Motion at the Primary Joint (Flare-up Site) at Weeks 6 and 12 [Time Frame: Baseline, Weeks 6 and 12]

Percentage of Subjects With New HO at Weeks 6 and 12 [Time Frame: Weeks 6 and 12 (Day 84)]

Secondary ID(s)

PVO-1A-201

2014-001453-17

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 24/06/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02190747