SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT02979769

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 2, Open-Label, Efficacy and Safety Study of an RARĪ³ Specific Agonist (Palovarotene) to Prevent Heterotopic Ossification in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)

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 (RARĪ³) agonists such as palovarotene (PVO) to prevent HO following injury. This 24-month study will (1) continue to follow FOP subjects from France who completed Clementia Study PVO-1A-201; (2) enroll up to eight additional new French subjects who have achieved at least 90% skeletal maturity; and (3) evaluate the ability of different palovarotene dosing regimens to prevent HO in these subjects.

NCT02979769 Fibrodysplasia Ossificans Progressiva
MeSH:Myositis Ossificans Ossification, Heterotopic
HPO:Ectopic ossification

2 Interventions

Name: Palovarotene dose level 1

Description: Palovarotene will be taken orally once daily at approximately the same time each day.
Type: Drug
Group Labels: 1

Palovarotene dose level 1

Name: Palovarotene dose level 2

Description: Palovarotene will be taken orally once daily at approximately the same time each day.
Type: Drug
Group Labels: 1

Palovarotene dose level 2


Primary Outcomes

Measure: Percentage of flare-ups with no new HO as assessed by low-dose CT scan

Time: Flare-up Day 84

Secondary Outcomes

Measure: Amount (volume) of new HO at the flare-up site as assessed by low-dose CT scan.

Time: baseline, Flare-up Day 84/end-of-treatment (EOT)

Measure: Amount (volume) of new HO overall as assessed by low-dose whole body CT scan, excluding head.

Time: baseline, Study Months 12 and 24

Measure: Active range of motion measured by goniometer at the flare-up site.

Time: baseline, Flare-up Day 84/EOT

Measure: Range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).

Time: baseline, Flare-up Day 84/EOT; Study Months 12 and 24

Measure: Number of flare-ups per subject-month exposure.

Time: study start date to study end date (up to 24 months)

Measure: Subject and Investigator global assessment of movement.

Time: Flare-up Day 84/EOT

Measure: Age-appropriate patient-reported assessment of physical function.

Time: baseline, Flare-up days 28, 56, 84/EOT; Study Months 12 and 24

Measure: Use of assistive devices and adaptations for daily living by FOP subjects.

Time: baseline, Flare-up Day 84/EOT; Study Months 12 and 24

Measure: Plasma biomarker levels.

Time: baseline, Flare-up Days 28, 56, and 84/EOT; Study Months 12 and 24

Measure: Presence of soft tissue swelling and/or cartilage by magnetic resonance imaging (or ultrasound).

Time: Flare-up Day 84/EOT

Measure: Pain at the flare-up site using a numeric rating scale for each symptom.

Time: baseline, Flare-up Days 14, 28, 42, 56, 70, and 84/EOT

Measure: Swelling at the flare-up site using a numeric rating scale for each symptom.

Time: baseline, Flare-up Days 14, 28, 42, 56, 70, and 84/EOT

Measure: Duration of active, symptomatic flare-up.

Time: subject-reported symptom start date to documented symptom end date assessed up to 84 days/EOT

Measure: Amount of new heterotopic bone formed at the original flare-up site as assessed by low-dose CT scan (or plain radiograph for those unable to undergo CT scan).

Time: baseline, Study Month 12 (Pediatric Cohort only)

Measure: Safety evaluation including adverse events and clinical safety laboratory parameters.

Time: Flare-up Days 1 (the first day of dosing), 7, 14, 28, 42, 56, 70, and 84/EOT; Study Months 3, 6, 9, 12, 15, 18, 21, and 24

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 R206H

Inclusion Criteria: - Completion of Study PVO-1A-201; or new Adult Cohort subjects with confirmed R206H mutation who (1) have had at least two symptomatic flare-ups in the past 2 years, but no flare-up symptoms within the past 4 weeks; (2) have a Cumulative Analogue Joint Involvement for FOP (CAJIS) score of 6-16 (inclusive); and (3) are able to receive 5 mg palovarotene daily. --- R206H ---



HPO Nodes


HPO: