A Study to Document and to Further Describe Long-term Safety and Effectiveness of Palovarotene in Participants With Fibrodysplasia Ossificans Progressiva (FOP) (FOPal)

An International Observational Registry Study to Further Describe Long-term Safety and Effectiveness of Palovarotene in Patients With Fibrodysplasia Ossificans Progressiva (FOP)

The participants in this registry study will have fibrodysplasia ossificans progressiva (FOP).

FOP is an ultra-rare, severely disabling disease characterized by new bone formation in areas of the body where bone is not normally present (heterotopic ossification (HO)).

HO is often preceded by painful, recurrent episodes of soft tissue swelling (flare-ups).

This registry study will take place in countries where the treatment, known as palovarotene has been approved for use. Participants will already be receiving palovarotene as prescribed by their treating physician according to locally approved product information.

The main aim of this study will be to collect and assess real-world safety data on children and adult participants with FOP treated with palovarotene.

This study will also describe the effectiveness of this treatment, including the effect on everyday activities and physical performance

Study Overview

• Status: Not yet recruiting
• Conditions: Fibrodysplasia Ossificans Progressiva

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Ipsen Clinical Study Enquiries; Phone Number: see email; Email: clinical.trials@ipsen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults and children with FOP who have been prescribed palovarotene, as per local label, by their treating physician for which informed consent has been obtained and maintained. Participants cannot be included if they are currently participating in a palovarotene clinical trial or an interventional clinical trial for FOP or if they have any contraindication for palovarotene (except for pregnant women who have previously received and discontinued palovarotene at any time during the pregnancy and who will be included for safety follow-up).

Description

Inclusion Criteria :

• Adult or child with FOP who have been prescribed palovarotene (prior to and independently of the decision to enroll the patient in this registry study and as per local label) by their treating physician according to the locally approved product information;
• Signed informed consent as per local regulations must be obtained and maintained. Consent/assent from the participant should be obtained as appropriate before any registry study data collection are conducted. If applicable, parents or legally authorized representatives must give signed informed consent.

Exclusion Criteria :

• Currently participating in a palovarotene clinical trial;
• Currently participating in any interventional clinical trial for FOP;
• Have any contraindication to palovarotene as per the locally approved label (except for pregnant women who have previously received and discontinued palovarotene at any time during the pregnancy and who will be included for safety follow-up).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), whether or not they are considered as related to palovarotene	Adverse events will be coded according to MedDRA and will be classified by Preferred Term (PT) and system organ class (SOC).	From Baseline up to 30 days after the last palovarotene dose.
Percentage of Participants With Serious and Non-serious treatment-related TEAEs	Adverse events will be coded according to MedDRA and will be classified by PT and SOC.	From Baseline up to 30 days after the last palovarotene dose.
Percentage of Participants With all serious TEAEs, whether or not they are considered as related to the palovarotene	Adverse events will be coded according to MedDRA and will be classified by PT and SOC.	From Baseline up to 30 days after the last palovarotene dose.
Percentage of Participants With nonserious TEAEs whether or not they are considered as related to the palovarotene.	Adverse events will be coded according to MedDRA and will be classified by PT and SOC.	From Baseline up to 30 days after the last palovarotene dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Cumulative Analogue Joint Involvement Scale (CAJIS) total score	The CAJIS is an objective measure of joint movement completed by the Investigator to document total joint involvement. The CAJIS total score is calculated as the sum of the scores of all joints/regions and ranges from 0 (no involvement) to 30 (maximally involved).	From Baseline and every six months up to eleven years.
Change from Baseline in use of assistive devices	Assistive devices is a questionnaire to assess the assistive devices used by particpants and adaptations for their daily living.	From Baseline and every six months up to eleven years.
Change from Baseline in percent of worst score for Fibrodysplasia Ossificans Progressiva-Physical Function Questionnaire (FOP-PFQ) total score	Fibrodysplasia Ossificans Progressiva-Physical Function Questionnaire (FOP-PFQ) consists of questions which are scored on a scale of 1 to 5, lower scores indicating that the participant has more difficulties.	From Baseline and every six months up to eleven years.
Change from Baseline in observed and percent predicted Forced Vital Capacity (FVC)	The lung function parameters of observed FVC (liters) and percent predicted FVC are obtained by spirometry.	From Baseline and every six months up to eleven years.
Change from Baseline in observed and percent predicted Forced Expiratory Volume in one second (FEV1)	The lung function parameters of observed FEV1 (liters) and percent predicted FEV1 are obtained by spirometry.	From Baseline and every six months up to eleven years.
Change from Baseline in absolute and percent predicted FEV1/FVC ratio	The lung function parameters of the absolute and percent predicted FEV1/FVC ratio are obtained by spirometry.	From Baseline and every six months up to eleven years.
Change from Baseline in observed and percent predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO)	The lung function parameters of observed (traditional unit of mL/min/mmHg or SI unit of mmol/min/kPa) and percent predicted DLCO is obtained by the DLCO test.	From Baseline and every six months up to eleven years.
Change from Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) physical and mental function (mean global physical and mental health score converted into T-scores) for participants ≥15 years old	PROMIS Global Health Scale for the adult version, the global physical health and global mental health scores will be calculated as follows: Global physical health scores will be calculated as the sum of scores from Questions 3, 6, 7 and 8 and will range from 4 (worse health) to 20 (better health);; Global mental health scores will be calculated as the sum of scores from Questions 2, 4, 5 and 10 and will range from 4 (worse health) to 20 (better health).	From Baseline and every six months up to eleven years.
Change from Baseline in PROMIS overall quality of life (QoL) (mean total score converted into T-scores) for participants <15 years old	PROMIS Global Health Scale for the paediatric version, the total score will be calculated as the sum of scores from the first 7 questions and will range from 7 (worse health) to 35 (better health). If more than 3 questions contributing to the total score are missing, the total score will not be calculated. It will be considered as missing.	From Baseline and every six months up to eleven years.
Change from Baseline in annualized number of Investigator-reported flare-ups by body location and overall	The annualized number of flare-ups will be derived from the number of flare-ups the participant experienced since last visit.	From Baseline and every six months up to eleven years.
Number of flare-up outcomes	Number of flare-up outcomes as measured by new bone growth, restricted movement at each visit will be reported.	From Baseline and every six months up to eleven years.
Flare-up Duration	Flare-up duration will be assessed by body location and overall, at each visit.	From Baseline and every six months up to eleven years.
Number of flare-ups		From 12 months before inclusion Baseline up to eleven years.
Percentage of participants with new bone growth overall and by flare-up status	The number of extra bone growths, location of the extra bone growth, whether it was preceded by injury, illness, vaccination and/or other events, whether it was preceded by pain, soft tissue swelling, decreased range of motion, stiffness, redness, or warmth, extra bone growth start and stop date and whether it is ongoing, will be collected.	From Baseline and every six months up to eleven years.
Movement mobility change	Assessed by key body location: better movement/the same movement/slightly worse movement/moderately worse movement/severely worse movement)	From Baseline and annualy up to eleven years.
Number of locations impacted per participant		From Baseline and annualy up to eleven years.
Evolution of impacted location (how many times a location is impacted) per location		From Baseline and annualy up to eleven years.
Movement mobility outcomes		From Baseline and annualy up to eleven years.
Mean dose/year of palovarotene for chronic treatment		From Baseline and every six months up to eleven years.
Mean dose/cycle of palovarotene for flare-up treatment		From Baseline and every six months up to eleven years.
Incidence of pregnancy	A pregnant participant will be followed throughout the pregnancy and the health status of the baby will be verified	From Baseline and every month up to 30 days of the last palovarotene dose.
Description of pregnancy outcomes	A pregnant participant will be followed throughout the pregnancy.	From the signing of the ICF and the participant will be followed throughout the pregnancy (From Baseline and every month up to 30 days of the last palovarotene dose) and the health status of the baby will be verified up until one year of age
Change from Baseline in height velocity	Height velocity will be derived for growing children.	From Baseline and every six months up to eleven years.
Mean difference between chronological age and bone age	Bone age (assessment as per the SmPC/PI) will be collected for growing children. Chronological age will be derived for growing children.	From Baseline and every six months up to eleven years.
Frequency of premature physeal closure overall	Epiphyseal status ("open" or "closed") (assessment as per the SmPC/PI) will be collected for growing children.	From baseline up to 30 days of the last palovarotene dose
Percentage of participants with any fractures overall	Assessed by radiological imaging and clinical examination.	From baseline up to 30 days of the last palovarotene dose

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical, Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): December 31, 2033
• Study Completion (Estimated): January 31, 2034

Study Registration Dates

• First Submitted: October 6, 2023
• First Submitted That Met QC Criteria: October 13, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Myositis; Myositis Ossificans
• Other Study ID Numbers: CLIN-60120-453

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing 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.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No