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. (PIVOINE)

• ClinicalTrials.gov Identifier: NCT05027802
• Recruitment Status: Recruiting
• First Posted: August 30, 2021
• Last Update Posted: March 14, 2023
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fibrodysplasia Ossificans Progressiva (FOP)	Drug: Palovarotene	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 87 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rollover Study; Multicentre, Phase III, Open-label 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 Study PVO-1A-301 or PVO-1A-202/PVO-1A-204 and May Benefit From Palovarotene Therapy.
• Actual Study Start Date: March 14, 2022
• Estimated Primary Completion Date: November 11, 2024
• Estimated Study Completion Date: November 11, 2024

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

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

Outcome Measures

Primary Outcome Measures :

1. Incidence and description of all serious and non-serious treatment-emergent adverse events (TEAEs) whether or not they are considered as related to the study intervention; [ Time Frame: Three years. ]
   Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will be classified by PT (Preferred Term) and SOC (System Organ Class)

Secondary Outcome Measures :

1. Raw values and change from the Inclusion Visit in CAJIS (Cumulative Analogue Joint Involvement Scale) total score [ Time Frame: Every six months up to three years ]
2. Raw values and shift from the Inclusion Visit in the use of assistive devices and adaptations for daily living [ Time Frame: Every six months up to three years ]
   The use of assistive devices and adaptations for daily living will be collected using the FOP assistive devices assessment.
3. Raw values and change from the Inclusion Visit in % of worst score for total score, upper extremities subscore and mobility subscore [ Time Frame: Every six months up to three years ]
   Using the adult form of the FOP-PFQ (FOP-Physical Function Questionnaire) for all participants
4. Frequency of healthcare services utilization [ Time Frame: Three years ]
5. Raw values and change from the Inclusion Visit in observed and % predicted FVC (Forced Vital Capacity) [ Time Frame: Every six months up to three years ]
6. Raw values and change from the Inclusion Visit in observed and % predicted FEV1 (Forced Expiratory Volume in One Second) [ Time Frame: Every six months up to three years ]
7. Raw values and change from the Inclusion Visit in absolute and % predicted FEV1/FVC ratio [ Time Frame: Every six months up to three years ]
8. Raw values and change from the Inclusion Visit in observed and % predicted DLCO (Diffusion Capacity of the Lung for Carbon Monoxide) [ Time Frame: Every six months up to three years ]
9. Raw values and change from the Inclusion Visit in physical and mental function (mean global physical and mental health score converted into T-scores) [ Time Frame: Every six months up to three years ]
   Using the adult form of the PROMIS (Patient Reported Outcomes Measurement Information System) Global Health Scale for all participants
10. Raw values and change from the Inclusion Visit in number of investigator-reported flareups, flare-up outcomes (new bone growth, restricted movement) and flare-up duration by body location and overall; [ Time Frame: Every six months up to three years ]
11. Percentage of participants with new bone growth overall and by flare-up status [ Time Frame: Every six months up to three years ]

Eligibility Criteria

• Ages Eligible for Study: 14 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Ipsen Recruitment Enquiries; see email; clinical.trials@ipsen.com

Locations

United States, California

University of California San Francisco (UCSF); Recruiting

San Francisco, California, United States, 94143

United States, Minnesota

Mayo Clinic; Active, not recruiting

Rochester, Minnesota, United States, 55905

United States, Pennsylvania

Children's Hospital of Philidelphia; Active, not recruiting

Philadelphia, Pennsylvania, United States, 19104

The Perelman School of Medicine - The University of Pennsylvania; Active, not recruiting

Philadelphia, Pennsylvania, United States, 19104

Argentina

Hospital Italiano de Buenos Aires; Recruiting

Buenos Aires, Argentina, C1181ACH

Australia, New South Wales

Royal North Shore Hospital; Active, not recruiting

Saint Leonards, New South Wales, Australia, 2065

Canada

Toronto General Hospital; Active, not recruiting

Toronto, Canada, M5T 2S8

France

Groupe Hospitalier Necker Enfants Malades; Active, not recruiting

Paris, France, 75015

Italy

Istituto Giannina Gaslini; Active, not recruiting

Genoa, Italy, 16147

Sweden

Norrlands Universitetssjukhus; Active, not recruiting

Umeå, Sweden, 90737

United Kingdom

Royal National Orthopaedic Hospital; Active, not recruiting

London, United Kingdom, HA7 4LP

Sponsors and Collaborators

Ipsen

Investigators

• Study Director: Ipsen Medical Director; Ipsen

More Information

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT05027802
• Other Study ID Numbers: CLIN-60120-452; 2021-002244-70 ( EudraCT Number )
• First Posted: August 30, 2021
• Last Update Posted: March 14, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• 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/).
• URL: https://vivli.org/members/ourmembers/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Myositis Ossificans; Myositis; Muscular Diseases; Musculoskeletal Diseases