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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)

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ClinicalTrials.gov Identifier: NCT05027802
Recruitment Status : Recruiting
First Posted : August 30, 2021
Last Update Posted : September 9, 2022
Sponsor:
Information provided by (Responsible Party):
Ipsen

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

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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


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.




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 ]


Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

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): NCT05027802


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

Locations
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United States, California
University of California San Francisco (UCSF) Recruiting
San Francisco, California, United States, 94143
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 Recruiting
Philadelphia, Pennsylvania, United States, 19104
Argentina
Hospital Italiano de Buenos Aires Not yet recruiting
Buenos Aires, Argentina, C1181ACH
Australia, New South Wales
Royal North Shore Hospital 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 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
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Study Director: Ipsen Medical Director Ipsen
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Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT05027802    
Other Study ID Numbers: CLIN-60120-452
2021-002244-70 ( EudraCT Number )
First Posted: August 30, 2021    Key Record Dates
Last Update Posted: September 9, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Where patient data can be anonymised, Ipsen will share all individual participant data that underlie the results reported in the published journal article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available.
Time Frame: Data are available beginning 6 months and ending 5 years after the publication of the findings in a journal; after this time, only raw data may be available.
Access Criteria: Proposals should be submitted to DataSharing@ipsen.com and will be assessed by a scientific review board.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Myositis Ossificans
Myositis
Muscular Diseases
Musculoskeletal Diseases