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 : Active, not recruiting
First Posted : October 18, 2017
Last Update Posted : August 2, 2021
|Condition or disease||Intervention/treatment||Phase|
|Fibrodysplasia Ossificans Progressiva||Drug: Palovarotene||Phase 3|
One primary objective is to evaluate the efficacy of palovarotene in decreasing new HO in subjects with FOP as assessed by low-dose, whole body computed tomography (WBCT), excluding head, compared to untreated subjects from Clementia's FOP natural history study (Study PVO-1A-001, NHS). The other primary objective is to evaluate the safety of palovarotene in subjects with FOP.
This is a Phase 3, multicenter, open-label study that will be conducted in three parts: Part A, the main part of the study; Part B, the 24-month extension. Eligible subjects will receive a chronic/flare-up dosing regimen of palovarotene for 48 months as follows:
- Chronic treatment: orally administered 5 mg palovarotene once daily for 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 will be weight-adjusted in skeletally immature subjects (those under the age of 18 years with less than 90% skeletal maturity on hand/ wrist x-rays performed at Screening).
And Part C, the up-to-2-year post last dose of study treatment follow-up for skeletally immature subjects. No new subjects will be enrolled into Part C. Subjects who were enrolled in Parts A or B who have discontinued the study and were skeletally immature will be invited back to participate in the off-treatment Part C safety follow-up.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 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 28, 2017|
|Actual Primary Completion Date :||January 24, 2020|
|Estimated Study Completion Date :||November 2022|
Experimental: Palovarotene Chronic/Flare-Up Regimen
Subjects will receive 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 will be adjusted for weight in skeletally immature subjects.)
Palovarotene will be taken orally once daily at approximately the same time each day following a meal.
- Change in New HO Volume [ Time Frame: Screening, every 6 months to 2 years ]Annualized change in new HO volume as assessed by low-dose, WBCT (excluding head) compared to untreated subjects from the NHS.
- Subjects with New HO [ Time Frame: Screening, every 6 months for 2 years, then annually up to 4 years ]The proportion of subjects with any new HO.
- Number of Body Regions with HO [ Time Frame: Screening, every 6 months for 2 years, then annually up to 4 years ]Change from baseline in the number of body regions with new HO.
- Subjects with Flare-Ups [ Time Frame: Up to 4 years ]The proportion of subjects reporting flare-ups.
- Rate of Flare-Ups [ Time Frame: Up to 4 years ]The rate of flare-ups per subject-month exposure.
- Incidence of Adverse Events [ Time Frame: Up to 4 years ]Monitor adverse events.
- Palovarotene Area Under the Curve (AUC) [ Time Frame: Predose, and 3, 6, 10, and 24 hours postdose ]Determination of AUC at steady-state assessed during treatment with 5, 10, and 20 mg palovarotene.
- Range of Motion [ Time Frame: Screening, every 6 months up to 4 years ]Change from baseline in range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).
- FOP-Physical Function Questionnaire [ Time Frame: Screening, every 6 months up to 4 years ]Change from baseline in physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (PFQ).
- PROMIS Global Health Scale [ Time Frame: Screening, every 6 months up to 4 years ]Change from baseline in physical/mental function using age-appropriate forms of the PROMIS Global Health Scale.
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 - 200 1st Street Southwest|
|Rochester, Minnesota, United States, 55905|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Hospital Italiano de Buenos Aires, Tte General Juan Domingo Peron 4190|
|Buenos Aires, Argentina, C1199ABB|
|Australia, New South Wales|
|Royal North Shore Hospital|
|Saint Leonards, New South Wales, Australia, 2065|
|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, Department of Pediatrics, Unit of Rare Diseases|
|Genova, Liguria, Italy, 16148|
|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|