We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02279095




Registration number
NCT02279095
Ethics application status
Date submitted
26/10/2014
Date registered
30/10/2014
Date last updated
3/05/2021

Titles & IDs
Public title
An Open-Label Extension Study of Palovarotene Treatment in FOP
Scientific title
A Phase 2, Open-Label Extension, Efficacy and Safety Study of a RAR? Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
Secondary ID [1] 0 0
2014-002496-28
Secondary ID [2] 0 0
PVO-1A-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fibrodysplasia Ossificans Progressiva 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 dose level 1
Treatment: Drugs - Palovarotene dose level 2
Treatment: Drugs - Palovarotene dose level 3
Treatment: Drugs - Palovarotene dose level 4

Experimental: Palovarotene dose level 1 (completed) - Subjects received weight-adjusted doses of palovarotene equivalent to 10 mg once daily for 14 days, followed by 5 mg once daily for 28 days for an eligible flare-up (Part A).

Experimental: Palovarotene dose level 2 - Subjects with at least 90% skeletal maturity received 5 mg palovarotene once daily for up to 24 months; and 20 mg palovarotene for 28 days, followed by 10 mg for 56 days for eligible flare-ups (Part B).

Experimental: Palovarotene dose level 3 - Subjects with less than 90% skeletal maturity received weight-adjusted doses of 20 mg palovarotene for 28 days, followed by 10 mg for 56 days for eligible flare-ups (Part B).

Experimental: Palovarotene dose level 4 - All subjects will receive 5 mg palovarotene once daily for up to 36 months; and 20 mg palovarotene for 28 days, followed by 10 mg for 56 days for eligible flare-ups (Part C). Doses are adjusted for weight in skeletally immature subjects


Treatment: Drugs: Palovarotene dose level 1
Palovarotene was taken orally once daily at approximately the same time each day.

Treatment: Drugs: Palovarotene dose level 2
Palovarotene will be taken orally once daily at approximately the same time each day.

Treatment: Drugs: Palovarotene dose level 3
Palovarotene will be taken orally once daily at approximately the same time each day.

Treatment: Drugs: Palovarotene dose level 4
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
Change in New HO Volume - Annualized change in new HO volume as assessed by low-dose, WBCT (excluding head).
Timepoint [1] 0 0
Screening, every 12 months up to 60 months
Secondary outcome [1] 0 0
Subjects with New HO - The proportion of subjects with any new HO.
Timepoint [1] 0 0
Baseline, every 12 months up to 60 months
Secondary outcome [2] 0 0
Range of Motion - Change from baseline in range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).
Timepoint [2] 0 0
Baseline, every 6 months up to 60 months
Secondary outcome [3] 0 0
FOP-Physical Function Questionnaire - Change from baseline in physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (PFQ).
Timepoint [3] 0 0
Baseline, every 6 months up to 60 months
Secondary outcome [4] 0 0
PROMIS Global Health Scale - Change from baseline in mental and/or physical health function for subjects using age-appropriate forms of the PROMIS Global Health Scale.
Timepoint [4] 0 0
Baseline, every 6 months up to 60 months
Secondary outcome [5] 0 0
Incidence of Adverse Events - Monitor adverse events.
Timepoint [5] 0 0
every month up to 60 months
Secondary outcome [6] 0 0
Pharmacokinetics of Palovarotene - Steady-state pharmacokinetics assessed during treatment with 10 and 20 mg palovarotene.
Timepoint [6] 0 0
Pre-dose and 3, 6, 10, and 24 hours post-dose

Eligibility
Key inclusion criteria
- Completion of Study PVO-1A-202/Part B.

- Written, signed, and dated informed consent and, for subjects who are minors,
age-appropriate subject assent (performed according to local regulations).

- Accessible for treatment with palovarotene and follow-up (able and willing to travel
to a site for the initial and all follow-up clinic visits).

- Able to undergo low-dose, WBCT scan, excluding head.

- Females of child-bearing potential must have a negative blood or urine pregnancy test
(with sensitivity of at least 50 mIU/mL) prior to administration of palovarotene.

- Male and FOCBP subjects must agree to remain abstinent from heterosexual sex during
treatment and for 1 month after treatment or, if sexually active, to use two effective
methods of birth control during and for 1 month after treatment. Additionally,
sexually active FOCBP subjects must already be using two effective methods of birth
control 1 month before treatment is to start. Specific risk of the use of retinoids
during pregnancy, and the agreement to remain abstinent or use two effective methods
of birth control will be clearly defined in the informed consent and the subject or
legally authorized representatives.
Minimum age
6 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any reason that, in the opinion of the Investigator, would lead to the inability of
the subject and/or family to comply with the protocol.

- Amylase or lipase >2x above the upper limit of normal or with a history of
pancreatitis.

- Elevated aspartate aminotransferase or alanine aminotransferase >2.5x the upper limit
of normal.

- Fasting triglycerides >400 mg/dL with or without therapy.

- If currently using vitamin A or beta carotene, multivitamins containing vitamin A or
beta carotene, herbal preparations containing vitamin A or beta carotene, or fish oil,
and unable or unwilling to discontinue use of these products during palovarotene
treatment.

- Subjects experiencing suicidal ideation (type 4 or 5) or any suicidal behavior within
the past month as defined by the Columbia Suicide Severity Rating Scale (C-SSRS).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland University of Technology (QUT) Institute of Health and Biomedical Innovation (IHBI) - Woolloongabba
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
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
France
State/province [5] 0 0
Paris
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Middlesex

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Clementia Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease
characterized by heterotopic ossification (HO) often associated with painful, recurrent
episodes of soft tissue swelling (flare-ups) that lead to ankyloses of major joints with
cumulative and irreversible loss of movement and disability. In this study, the ability of
palovarotene to prevent HO formation will be evaluated.
Trial website
https://clinicaltrials.gov/show/NCT02279095
Trial related presentations / publications
Shimono K, Tung WE, Macolino C, Chi AH, Didizian JH, Mundy C, Chandraratna RA, Mishina Y, Enomoto-Iwamoto M, Pacifici M, Iwamoto M. Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-? agonists. Nat Med. 2011 Apr;17(4):454-60. doi: 10.1038/nm.2334. Epub 2011 Apr 3. Erratum in: Nat Med. 2012 Oct;18(10):1592.
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

Summary results
Other publications