A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies.

NCT05027802 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CLIN-60120-4522021-002244-70
• Study Type: interventional
• Target: 61
• Locations: 10 countries
• Sites: 13

Brief Summary

The main objective of this study is to further evaluate the safety and efficacy of palovarotene in adult and paediatric participants with FOP. The aim of the study is also to ensure treatment continuity to participants who have completed one of the parent studies (Study PVO-1A-301, Study PVO-1A-202 and Study PVO-1A-204) and who, in the investigator's judgement, may benefit from palovarotene therapy.

Conditions

Fibrodysplasia Ossificans Progressiva (FOP)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events

  An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or significant medical event. A TEAE was defined as any AE that occurred after signing the informed consent form of this study or an ongoing AE from the parent study with a worsening in severity or relationship to the study treatment following transition to this study.

  From signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months

Secondary Outcomes (13)

• Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30

  Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

• Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30

  Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

• Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30

  Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

• Annualized Rate of Healthcare Utilization (HU) in Participants With Fibrodysplasia Ossificans Progressiva

  Up to approximately 32 months

• Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30

  Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30

Study Arms (1)

Palovarotene Chronic/Flare-Up Regimen

EXPERIMENTAL

Chronic treatment: participants will receive 5 mg palovarotene or the dose received during participation in the parent study at the time of transition to Study CLIN-60120-452 or prior to interrupting/stopping palovarotene treatment. Flare-up treatment: at the time of a flare-up (or substantial high-risk traumatic event likely to lead to a flare-up) participants will receive 20 mg palovarotene for 28 days, followed by 10 mg palovarotene for 56 days.

Drug: Palovarotene

Interventions

Palovarotene DRUG

Palovarotene will be taken orally once daily at approximately the same time each day.

Palovarotene Chronic/Flare-Up Regimen

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has completed the EOS or End of Treatment Visit of Study PVO-1A-301 or PVO-1A-202 (PVO-1A-202 Parts C and D correspond to Study PVO-1A-204 in France) and did not previously withdraw consent from any of the parent studies to be eligible for Study CLIN-60120-452.
• Participant must be ≥14 years of age (aligned with the age of treated participants in the ongoing parent studies PVO-1A-301 and PVO-1A-202/PVO-1A-204) and qualify as 100% skeletally mature (if \<18 years, based on assessments carried out at parent EOS Visit; if ≥18 years, automatically considered 100% skeletally mature) or have reached final adult height based on investigator's assessment, at the time the Study CLIN- 60120-452 informed consent is signed.

You may not qualify if:

• Uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.
• Symptomatic vertebral fracture.
• Intercurrent known or suspected non-healed fracture at any location;
• Any other medical condition/clinically significant abnormalities that would expose the participant to undue risk or interfere with study assessments.
• Amylase or lipase \>2× above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
• Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.5× ULN.
• Fasting triglycerides \>400 mg/dL with or without therapy.
• Current use of vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment.
• Concurrent treatment with tetracycline or any tetracycline derivatives due to the potential increased risk of pseudotumor cerebri.
• Use of concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.
• Palovarotene is reimbursed in the country where the study is being conducted.
• Any reason that, in the opinion of the investigator, would lead to the inability of the participant and/or family to comply with the protocol.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (13)

University of California San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Children's Hospital of Philidelphia

Philadelphia, Pennsylvania, 19104, United States

Location

The Perelman School of Medicine - The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1181ACH, Argentina

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Hospital Israelita Albert Einstein

Morumbi, São Paulo, 05652-900, Brazil

Location

Toronto General Hospital

Toronto, M5T 2S8, Canada

Location

Groupe Hospitalier Necker Enfants Malades

Paris, 75015, France

Location

Istituto Giannina Gaslini

Genoa, 16147, Italy

Location

Hospital Universitario Ramon y Cajal

Colmenar Viejo, 28034, Spain

Location

Norrlands Universitetssjukhus

Umeå, 90737, Sweden

Location

Royal National Orthopaedic Hospital

London, HA7 4LP, United Kingdom

Location

Related Links

• Lay language results summary

MeSH Terms

Conditions

Myositis Ossificans

Interventions

Palovarotene

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen Bioscience Inc.

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: August 30, 2021
• Study Start: March 14, 2022
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: June 22, 2025
• Results First Posted: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Locations

AR (1); FR (1); IT (1); BR (1); CA (1); ES (1); SE (1); GB (1); US (4); AU (1)