Fibrodysplasia Ossificans ProgressivaPhase 3MOVENCT03312634
An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.
A Phase 3 study testing Palovarotene in people with Fibrodysplasia Ossificans Progressiva, run by Clementia Pharmaceuticals Inc. at 16 sites in 11 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Fibrodysplasia Ossificans Progressiva
- What is being tested?
- Palovarotene
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 16 sitesin 11 countries
- Study dates
- 30 Nov 2017to 7 Sep 2022
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
16 sites in 11 countries.
16 sites in 11 countries
United States4 sites
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Pennsylvania, Internal Medicine
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
University of California San Francisco, Division of Endocrinology and Metabolism
San Francisco, California, 94143
Australia2 sites
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065
Queensland University of Technology
Woolloongabba, Queensland, 4102
Canada2 sites
Hospital for Sick Children, 555 University Avenue
Toronto, Ontario, M5G 1X8
Toronto General Hospital
Toronto, Ontario, M5G 2C4
Argentina1 site
Hospital Italiano de Buenos Aires, Tte General Juan Domingo Peron 4190
Buenos Aires, C1199ACH
Brazil1 site
Hospital Israelita Albert Einstein
São Paulo, São Paulo, 05652-900
Spain1 site
Hospital Universitari i Politècnic La Fe, Unidad de Reumatología Pediatrica
Valencia, Avinguda de Fernando Abril Martorell, Nº 106, 46026
United Kingdom1 site
Royal National Orthopaedic Hospital, Brockely Hill
Stanmore, HA7 4LP
About this study
Official title: 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.
Read the detailed description
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, Part B, the 2-year (24-month) extension and Part C was an up-to-2-year post last dose of study treatment follow-up for skeletally immature participants.
Participants in Part A and B received a chronic/flare-up dosing regimen of palovarotene for up to 4 years (48 months) as follows:
- Chronic treatment: orally administered 5 mg palovarotene once daily.
- 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).
In 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 safety follow-up. No new participants were enrolled into Part C.
- Conditions
- Fibrodysplasia Ossificans Progressiva
- Being tested
- Palovarotene
- Keywords
- Interventional study, Clinical trial phase 3, Efficacy and safety, Heterotopic ossification, Flare-up, Palovarotene, Retinoic acid receptor agonist, Retinoic acid receptor gamma agonist, Clementia, Myositis Ossificans Progressiva, Munchmeyer's Disease, FOP, FOP variants
- Medical subject headings
- Myositis Ossificans, Ossification, Heterotopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalovaroteneDrug
Palovarotene was taken orally once daily at approximately the same time each day following a meal.
| Study group | Role | What they receive |
|---|---|---|
| Palovarotene Chronic/Flare-Up Regimen | Experimental | Participants received 5 mg palovarotene once daily for up to 48 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.) Receives: Drug: Palovarotene |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized New Heterotopic Ossification (HO)
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.
Measured: Baseline (within one month of screening/Day 1) and up to 24 months
Secondary outcomes (4)
Percentage of Participants With Any New HO
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. Results are presented for overall ITT period.
Measured: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)
Number of Body Regions With New HO
All participants were analyzed for number of body regions with any new HO (new HO > 0 mm^3). The presence of HO across various body regions was analyzed using WBCT scan. Results are presented for overall ITT period
Measured: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)
Percentage of Participants With Flare-Ups
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.
Measured: Month 12
Ratio of Flare-Up Per Participant-Month of Exposure
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. Results are presented for overall ITT period.
Measured: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2017
- Study start30 Nov 2017
- Primary completion24 Jan 2020
- Study completion7 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Fibrodysplasia Ossificans ProgressivaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clementia Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03312634
- Sponsor's protocol ID
- PVO-1A-301
- Other IDs
- 2017-002541-29, 2017
- Acronym
- MOVE
- Status last verified
- Nov 2023
- First submitted
- 9 Oct 2017
- Last updated
- 29 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Shimono K, Tung WE, Macolino C, Chi AH, Didizian JH, Mundy C, Chandraratna RA, Mishina Y, Enomoto-Iwamoto M, Pacifici M, Iwamoto M. Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-gamma agonists. Nat Med. 2011 Apr;17(4):454-60. doi: 10.1038/nm.2334. Epub 2011 Apr 3.
PubMed 21460849Lindborg CM, Al Mukaddam M, Baujat G, Cho TJ, De Cunto CL, Delai PLR, Eekhoff EMW, Haga N, Hsiao EC, Morhart R, de Ruiter R, Scott C, Seemann P, Szczepanek M, Tabarkiewicz J, Pignolo RJ, Kaplan FS. Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility. Clin Orthop Relat Res. 2023 Dec 1;481(12):2447-2458. doi: 10.1097/CORR.0000000000002672. Epub 2023 May 8.
PubMed 37156007Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Brown MA, Cheung AM, De Cunto C, Delai P, Haga N, Kannu P, Keen R, Le Quan Sang KH, Mancilla EE, Marino R, Strahs A, Kaplan FS. Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP). J Bone Miner Res. 2023 Mar;38(3):381-394. doi: 10.1002/jbmr.4762. Epub 2023 Jan 25.
PubMed 36583535