Clinical trial NCT05027802: 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.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fibrodysplasia Ossificans Progressiva (FOP)
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2021-08-30
Enrollment: 61
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: From signing the informed consent form (Day 1) up to 30 days post last dose, approximately 32 months
Secondary outcomes:
measure: Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: 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
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: 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
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: Annualized Rate of Healthcare Utilization (HU) in Participants With Fibrodysplasia Ossificans Progressiva
timeFrame: Up to approximately 32 months
measure: Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30
timeFrame: Inclusion Visit (Day 1) and Months 6, 12, 18, 24 and 30
measure: Number of Participants With Flare-ups and Flare-up Outcomes
timeFrame: Months 6, 12, 18 and 24
measure: Number of Participants With Flare-ups by Body Location
timeFrame: Months 6, 12, 18 and 24
measure: Duration of Flare-up at Months 6, 12, 18 and 24
timeFrame: Months 6, 12, 18 and 24
measure: Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24
timeFrame: Months 6, 12, 18 and 24
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Philadelphia
country: United States
facility: Children's Hospital of Philidelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Perelman School of Medicine - The University of Pennsylvania
state: Pennsylvania
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Morumbi
country: Brazil
facility: Hospital Israelita Albert Einstein
state: Sao-Paulo
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Paris
country: France
facility: Groupe Hospitalier Necker Enfants Malades
city: Genoa
country: Italy
facility: Istituto Giannina Gaslini
city: Colmenar Viejo
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: London
country: United Kingdom
facility: Royal National Orthopaedic Hospital
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: