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.

NCT ID: NCT05027802

Last Updated: 2025-06-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-14

Study Completion Date

2024-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Fibrodysplasia Ossificans Progressiva (FOP)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Palovarotene Chronic/Flare-Up Regimen

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.

Group Type EXPERIMENTAL

Palovarotene

Intervention Type DRUG

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

Interventions

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Palovarotene

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* History of allergy or hypersensitivity to retinoids, gelatin, lactose (note that lactose intolerance is not exclusionary) or palovarotene, or unresponsiveness to prior treatment with palovarotene.
* 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.
* Suicidal ideation (type 4 or 5) or any suicidal behaviour at the Inclusion Visit as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS).
* 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.
* Exposure to synthetic oral retinoids other than palovarotene within 4 weeks of the Inclusion Visit.
* 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.
Minimum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ipsen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

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University of California San Francisco (UCSF)

San Francisco, California, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Children's Hospital of Philidelphia

Philadelphia, Pennsylvania, United States

Site Status

The Perelman School of Medicine - The University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Site Status

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Site Status

Hospital Israelita Albert Einstein

Morumbi, São Paulo, Brazil

Site Status

Toronto General Hospital

Toronto, , Canada

Site Status

Groupe Hospitalier Necker Enfants Malades

Paris, , France

Site Status

Istituto Giannina Gaslini

Genoa, , Italy

Site Status

Hospital Universitario Ramon y Cajal

Colmenar Viejo, , Spain

Site Status

Norrlands Universitetssjukhus

Umeå, , Sweden

Site Status

Royal National Orthopaedic Hospital

London, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Canada France Italy Spain Sweden United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2021-002244-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLIN-60120-452

Identifier Type: -

Identifier Source: org_study_id

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