An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva. (MOVE)
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|ClinicalTrials.gov Identifier: NCT03312634|
Recruitment Status : Completed
First Posted : October 18, 2017
Results First Posted : March 14, 2023
Last Update Posted : March 14, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Fibrodysplasia Ossificans Progressiva||Drug: Palovarotene||Phase 3|
One of the primary objectives was to evaluate the efficacy of palovarotene in decreasing new HO in participants with FOP as assessed by low-dose, whole body computed tomography (WBCT), excluding head, compared to untreated participants from Clementia's FOP natural history study (Study PVO-1A-001, NHS). The other primary objective was to evaluate the safety of palovarotene in participants with FOP.
This study was conducted in three parts. Part A was the main part of the study and Part B, the 2-year (24-month) extension. Eligible participants received a chronic/flare-up dosing regimen of palovarotene for 4 years (48 months) as follows:
- Chronic treatment: orally administered 5 mg palovarotene once daily for 2 years (24 months).
- Flare-up treatment: orally administered 20 mg palovarotene once daily for 4 weeks (28 days) followed by orally administered 10 mg palovarotene once daily for 8 weeks (56 days). Flare-up treatment may be extended until the Investigator determines that the flare-up has resolved.
Note that all dosing was weight-adjusted in skeletally immature participants (those under the age of 18 years with less than 90% skeletal maturity on hand/wrist x-rays performed at Screening).
Part C was an up-to-2-year post last dose of study treatment follow-up for skeletally immature participants. No new participants were enrolled into Part C. Participants who were enrolled in Parts A or B who discontinued the study and were skeletally immature were invited back to participate in the off-treatment Part C safety follow-up.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||107 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||A multicenter, open-label study. NHS data (study PVO-1A-001) will be used as an external control in the analysis.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)|
|Actual Study Start Date :||November 30, 2017|
|Actual Primary Completion Date :||January 24, 2020|
|Actual Study Completion Date :||September 7, 2022|
Experimental: Palovarotene Chronic/Flare-Up Regimen
Participants received 5 mg palovarotene once daily for up to 24 months; and 20 mg palovarotene once daily for 28 days, followed by 10 mg for 56 days for flareups. (Dosing was adjusted for weight in skeletally immature subjects.)
Palovarotene was taken orally once daily at approximately the same time each day following a meal.
- Annualized New Heterotopic Ossification (HO) [ Time Frame: Baseline (within one month of screening/Day 1) and up to 24 months ]The annualized new HO was assessed by low-dose, whole body computed tomography (WBCT), excluding head. The weighted linear mixed effect method without square-root transformation and negatives included was used for annualized new HO analysis.
- Percentage of Participants With Any New HO [ Time Frame: Month 12 ]The new HO was assessed by WBCT scan. The percentage of participants with any new HO (volume > 0 mm^3) were analyzed using the Bayesian distribution.
- Number of Participants With Body Regions With New HO [ Time Frame: Month 12 ]The number of participants with any new HO (new HO > 0 mm^3) by number of body regions are reported. The presence of HO across various body regions was analyzed using WBCT scan.
- Percentage of Participants With Flare-Ups [ Time Frame: Month 12 ]Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary.
- Ratio of Flare-Up Per Participant-Month of Exposure Through Month 24 [ Time Frame: From Baseline (Day 1) up to Month 24 ]Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary. The flare-up rate per participant-month exposure was analyzed using a negative binomial regression.
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|Ages Eligible for Study:||4 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Key Inclusion Criteria:
- Written, signed, and dated informed subject/parent consent; and for subjects who are minors, age-appropriate assent (performed according to local regulations).
- Males or females at least 4 years of age.
- 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.
- No flare-up symptoms within the past 4 weeks, including at the time of enrollment.
- Abstinent or using two highly effective forms of birth control.
- Accessible for treatment and follow-up; able to undergo all study procedures including low-dose WBCT (excluding head) without sedation.
Key Exclusion Criteria:
- Weight <10 kg.
- Concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.
- Amylase or lipase >2x above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
- Elevated aspartate aminotransferase or alanine aminotransferase >2.5x ULN.
- Fasting triglycerides >400 mg/dL with or without therapy.
- Female subjects who are breastfeeding.
- Subjects with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.
- Simultaneous participation in another clinical research study (other than palovarotene studies) within 4 weeks prior to Screening; or within five half-lives of the investigational agent, whichever is longer.
- Any reason that, in the opinion of the Investigator, would lead to the inability of the subject and/or family to comply with the protocol.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03312634
|United States, California|
|University of California San Francisco, Division of Endocrinology and Metabolism|
|San Francisco, California, United States, 94143|
|United States, Minnesota|
|Mayo Clinic - PIN|
|Rochester, Minnesota, United States, 55905|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pennsylvania, Internal Medicine|
|Philadelphia, Pennsylvania, United States, 19104|
|Hospital Italiano de Buenos Aires, Tte General Juan Domingo Peron 4190|
|Buenos Aires, Argentina, C1199ACH|
|Australia, New South Wales|
|Royal North Shore Hospital|
|Saint Leonards, New South Wales, Australia, 2065|
|Queensland University of Technology|
|Woolloongabba, Queensland, Australia, 4102|
|Hospital Israelita Albert Einstein|
|Sao Paulo, SP, Brazil, 05652-900|
|Hospital for Sick Children, 555 University Avenue|
|Toronto, Ontario, Canada, M5G 1X8|
|Toronto General Hospital|
|Toronto, Ontario, Canada, M5G 2C4|
|Groupe Hospitalier Necker Enfants Malades|
|Paris, France, 75015|
|Istituto Giannina Gaslini|
|Genoa, Liguria, Italy, 16147|
|The University of Tokyo Hospital|
|Tokyo, Bunkyo-ku, Japan, 113-8655|
|Hospital Universitari i Politècnic La Fe, Unidad de Reumatología Pediatrica|
|Valencia, Avinguda De Fernando Abril Martorell, Nº 106, Spain, 46026|
|Umeå, Sweden, SE-90185|
|Royal National Orthopaedic Hospital, Brockely Hill|
|Stanmore, United Kingdom, HA7 4LP|
|Study Director:||Ipsen Medical Director||Ipsen|
Documents provided by Ipsen ( Clementia Pharmaceuticals Inc. ):
|Responsible Party:||Clementia Pharmaceuticals Inc.|
|Other Study ID Numbers:||
2017-002541-29 ( EudraCT Number )
|First Posted:||October 18, 2017 Key Record Dates|
|Results First Posted:||March 14, 2023|
|Last Update Posted:||March 14, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Undecided|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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