SNPMiner Trials (Home Page)
Report for Mutation R206H
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 3 clinical trials
Clinical Trials
1 A Natural History, Non-Interventional, Two-Part Study 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 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. This 3-year, non-interventional, two-part, natural history study is designed to gain insight into total body HO, FOP disease progression, the impact of FOP on subjects' physical functioning, and clinical features and biomarkers that may be useful in the diagnosis and monitoring of disease progression. This natural history study will also provide important information to inform the design of subsequent interventional trials.
NCT02322255 Fibrodysplasia Ossificans Progressiva MeSH:Myositis Ossificans
Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Fibrodysplasia Ossificans Progressiva Myositis Ossificans This is a multi-center, natural history, non-interventional, longitudinal study in subjects with classic FOP. --- R206H ---
Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Fibrodysplasia Ossificans Progressiva Myositis Ossificans This is a multi-center, natural history, non-interventional, longitudinal study in subjects with classic FOP. --- R206H --- --- R206H ---
Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Fibrodysplasia Ossificans Progressiva Myositis Ossificans This is a multi-center, natural history, non-interventional, longitudinal study in subjects with classic FOP. --- R206H --- --- R206H --- --- R206H ---
Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Inclusion Criteria: - Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation Exclusion Criteria: - Participation in an interventional clinical research study within the 4 weeks prior to enrollment Fibrodysplasia Ossificans Progressiva Myositis Ossificans This is a multi-center, natural history, non-interventional, longitudinal study in subjects with classic FOP. --- R206H --- --- R206H --- --- R206H --- --- R206H ---
Primary Outcomes
Measure: Change from baseline in the total body burden of heterotopic ossification as assessed by the optimal imaging modality (low-dose whole body CT [excluding head]). Time: Month 36Secondary Outcomes
Measure: Change from baseline in physical function as assessed by range of motion. Time: Month 12, Month 24, and Month 36Measure: Change from baseline in patient-reported use of assistive devices and adaptations. Time: Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36
Measure: Change from baseline in a disease-specific patient-reported outcome measure (FOP-Physical Function Questionnaire [FOP-PFQ]). Time: Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36
Measure: Change from baseline in a patient-reported measure of physical and mental health (PROMIS Global Health Scale). Time: Month 6, Month 12, Month 18, Month 24, Month 30, and Month 36
Measure: Change from baseline in biomarkers. Time: Month 12, Month 24, and Month 36
Measure: Flare-up progression as assessed by the change from baseline in heterotopic ossification at the flare-up site. Time: Flare-up initiation, Flare-up Days 42 and 84
Measure: Flare-up progression as assessed by the change from baseline in pain and swelling at the flare-up site. Time: Flare-up initiation, Flare-up Days 42 and 84
Measure: Flare-up progression as assessed by the change from baseline biomarkers. Time: Flare-up initiation, Flare-up Days 42 and 84
Measure: Flare-up progression as assessed by the change from baseline in physical function as assessed by range of motion. Time: Flare-up initiation, Flare-up Days 42 and 84
Measure: Flare-up progression as assessed by the change from baseline in a disease-specific patient-reported outcome measure (FOP-Physical Function Questionnaire [FOP-PFQ]). Time: Flare-up initiation, Flare-up Days 42 and 84
Measure: Flare-up progression as assessed by the change from baseline in a patient-reported outcome measure of physical and mental health (PROMIS Global Health Scale). Time: Flare-up initiation, Flare-up Days 42 and 84
2 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 Drug: Palovarotene dose level 1 Drug: Palovarotene dose level 2 MeSH:Myositis Ossificans Ossification, Heterotopic
HPO:Ectopic ossification
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 ---
Primary Outcomes
Measure: Percentage of flare-ups with no new HO as assessed by low-dose CT scan Time: Flare-up Day 84Secondary 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
3 A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO) often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to ankyloses of major joints with cumulative and irreversible loss of movement and disability.
NCT03312634 Fibrodysplasia Ossificans Progressiva Drug: Palovarotene MeSH:Myositis Ossificans
- Previous participation in Clementia's natural history study (NCT02322255); clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants reported to be associated with progressive HO (who have not participated in any Clementia-sponsored study); participants in Clementia's Phase 2 studies (NCT02279095 and NCT02979769) who cannot currently receive the chronic/flare-up regimen due to country of residence or those traveling long distances to participate in the Phase 2 studies. --- R206H ---
Primary Outcomes
Description: Annualized change in new HO volume as assessed by low-dose, WBCT (excluding head) compared to untreated subjects from the NHS.
Measure: Change in New HO Volume Time: Screening, every 6 months for 2 years, then annually up to 4 yearsSecondary Outcomes
Description: The proportion of subjects with any new HO.
Measure: Subjects with New HO Time: Screening, every 6 months for 2 years, then annually up to 4 yearsDescription: Change from baseline in the number of body regions with new HO.
Measure: Number of Body Regions with HO Time: Screening, every 6 months for 2 years, then annually up to 4 yearsDescription: The proportion of subjects reporting flare-ups.
Measure: Subjects with Flare-Ups Time: Up to 4 yearsDescription: The rate of flare-ups per subject-month exposure.
Measure: Rate of Flare-Ups Time: Up to 4 yearsDescription: Monitor adverse events.
Measure: Incidence of Adverse Events Time: Up to 4 yearsDescription: Determination of AUC at steady-state assessed during treatment with 5, 10, and 20 mg palovarotene.
Measure: Palovarotene Area Under the Curve (AUC) Time: Predose, and 3, 6, 10, and 24 hours postdoseOther Outcomes
Description: Change from baseline in range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).
Measure: Range of Motion Time: Screening, every 6 months up to 4 yearsDescription: Change from baseline in physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (PFQ).
Measure: FOP-Physical Function Questionnaire Time: Screening, every 6 months up to 4 yearsDescription: Change from baseline in physical/mental function using age-appropriate forms of the PROMIS Global Health Scale.
Measure: PROMIS Global Health Scale Time: Screening, every 6 months up to 4 years