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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05027802




Registration number
NCT05027802
Ethics application status
Date submitted
25/08/2021
Date registered
30/08/2021

Titles & IDs
Public title
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.
Scientific 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.
Secondary ID [1] 0 0
2021-002244-70
Secondary ID [2] 0 0
CLIN-60120-452
Universal Trial Number (UTN)
Trial acronym
PIVOINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fibrodysplasia Ossificans Progressiva (FOP) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Palovarotene

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.


Treatment: Drugs: Palovarotene
Palovarotene will be taken orally once daily at approximately the same time each day.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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;
Timepoint [1] 0 0
Three years.
Secondary outcome [1] 0 0
Raw values and change from the Inclusion Visit in CAJIS (Cumulative Analogue Joint Involvement Scale) total score
Timepoint [1] 0 0
Every six months up to three years
Secondary outcome [2] 0 0
Raw values and shift from the Inclusion Visit in the use of assistive devices and adaptations for daily living
Timepoint [2] 0 0
Every six months up to three years
Secondary outcome [3] 0 0
Raw values and change from the Inclusion Visit in % of worst score for total score, upper extremities subscore and mobility subscore
Timepoint [3] 0 0
Every six months up to three years
Secondary outcome [4] 0 0
Frequency of healthcare services utilization
Timepoint [4] 0 0
Three years
Secondary outcome [5] 0 0
Raw values and change from the Inclusion Visit in observed and % predicted FVC (Forced Vital Capacity)
Timepoint [5] 0 0
Every six months up to three years
Secondary outcome [6] 0 0
Raw values and change from the Inclusion Visit in observed and % predicted FEV1 (Forced Expiratory Volume in One Second)
Timepoint [6] 0 0
Every six months up to three years
Secondary outcome [7] 0 0
Raw values and change from the Inclusion Visit in absolute and % predicted FEV1/FVC ratio
Timepoint [7] 0 0
Every six months up to three years
Secondary outcome [8] 0 0
Raw values and change from the Inclusion Visit in observed and % predicted DLCO (Diffusion Capacity of the Lung for Carbon Monoxide)
Timepoint [8] 0 0
Every six months up to three years
Secondary outcome [9] 0 0
Raw values and change from the Inclusion Visit in physical and mental function (mean global physical and mental health score converted into T-scores)
Timepoint [9] 0 0
Every six months up to three years
Secondary outcome [10] 0 0
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;
Timepoint [10] 0 0
Every six months up to three years
Secondary outcome [11] 0 0
Percentage of participants with new bone growth overall and by flare-up status
Timepoint [11] 0 0
Every six months up to three years

Eligibility
Key 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.
Minimum age
14 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/11/2024
Actual
Sample size
Target
Accrual to date
Final
63
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
Argentina
State/province [4] 0 0
Buenos Aires
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao-Paulo
Country [6] 0 0
Canada
State/province [6] 0 0
Toronto
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Italy
State/province [8] 0 0
Genoa
Country [9] 0 0
Spain
State/province [9] 0 0
Colmenar Viejo
Country [10] 0 0
Sweden
State/province [10] 0 0
Umeå
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ipsen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
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.
Available to whom?
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/members/ourmembers/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05027802