SNPMiner Trials: Clinical Trial Report
Report for Clinical Trial NCT02979769
Developed by Shray Alag, 2019.
SNP Clinical Trial Gene
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.
Name: Palovarotene dose level 1
Description: Palovarotene will be taken orally once daily at approximately the same time each day.Type: Drug
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
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
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