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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02279095
Ethics application status
Date submitted
26/10/2014
Date registered
30/10/2014

Titles & IDs
Public title
An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)
Scientific title
A Phase 2, Open-Label Extension, Efficacy and Safety Study of a Retinoic Acid Receptor Gamma (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) - Participants received 10 mg palovarotene for 14 days, followed by 5 mg palovarotene for 28 days (or weight-based equivalent) for eligible flare-ups (Part A).

Experimental: Palovarotene dose level 2 - Participants with at least 90% skeletal maturity received 5 mg palovarotene 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 - Participants 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 participants will receive 5 mg palovarotene for up to 48 months and 20 mg palovarotene for 28 days, followed by 10 mg for 56 days for eligible flare-ups (Part C). Skeletally immature participants will receive weight-adjusted doses.


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
Parts A and B: Percentage of Flare-ups With No New Heterotopic Ossification (HO) at Week 12
Timepoint [1] 0 0
Baseline and Week 12
Primary outcome [2] 0 0
Parts B and C: Annualized Change in New HO Volume
Timepoint [2] 0 0
From Baseline (Day 1) up to end of 2 year follow-up period, approximately a maximum of 96 months
Secondary outcome [1] 0 0
Parts A and B: Percentage of Participants Across the 7 HO Scores at Month 12 of Part A; and Weeks 6 and 12 for Part B
Timepoint [1] 0 0
Part A: Baseline (pre-dose data from Study PVO-1A-201 for follow-up component and flare-up screening/Day 1 for flare-up component) and Month 12; Part B: Baseline (flare-up screening/baseline) and Weeks 6 and 12
Secondary outcome [2] 0 0
Parts A and B: Volume of New Heterotopic Bone Formed at Month 12
Timepoint [2] 0 0
Month 12
Secondary outcome [3] 0 0
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12
Timepoint [3] 0 0
Part A and B: At Week 12
Secondary outcome [4] 0 0
Parts A and B: Change From Baseline in Active Range of Motion (ROM) at Flare-up Site at Week 12
Timepoint [4] 0 0
Baseline and Week 12
Secondary outcome [5] 0 0
Part B: Change From Baseline in ROM at Week 12
Timepoint [5] 0 0
Baseline and Week 12
Secondary outcome [6] 0 0
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48
Timepoint [6] 0 0
Baseline and Months 6, 12, 18, 24, 30, 36, 42, and 48
Secondary outcome [7] 0 0
Part B: Participant and Investigator Global Assessment of Movement at Week 12
Timepoint [7] 0 0
Week 12
Secondary outcome [8] 0 0
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12
Timepoint [8] 0 0
Baseline and Weeks 2, 4, 6, 9, and 12
Secondary outcome [9] 0 0
Parts A and B: Change From Baseline in Physical Function at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B
Timepoint [9] 0 0
Part A: Baseline and Weeks 2, 4, 6, 9, and 12; and Part B: Baseline and Weeks 4, 8, and 12
Secondary outcome [10] 0 0
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48
Timepoint [10] 0 0
Baseline and Months 6, 12, 18, 24, 30, 36, 42, and 48
Secondary outcome [11] 0 0
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B
Timepoint [11] 0 0
Part A: Baseline and Weeks 2, 4, 6, 9, and 12; and Part B: Baseline and Weeks 4, 8, and 12
Secondary outcome [12] 0 0
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48
Timepoint [12] 0 0
Baseline and Months 6, 12, 18, 24, 30, 36, 42, and 48
Secondary outcome [13] 0 0
Parts A and B: Number of Any Assistive Devices and Adaptations by FOP Participants at Weeks 6 and 12 of Part A; and Week 12 of Part B
Timepoint [13] 0 0
Part A: Weeks 6 and 12; and Part B: Week 12
Secondary outcome [14] 0 0
Part A: Percentage of Responders at Week 12
Timepoint [14] 0 0
Week 12
Secondary outcome [15] 0 0
Parts A and B: Change From Baseline in Amount of Bone Formation Biomarker at Weeks 6 and 12 of Part A; and Week 12 of Part B
Timepoint [15] 0 0
Part A: Baseline and Weeks 6 and 12; and Part B: Baseline and Week 12
Secondary outcome [16] 0 0
Parts A and B: Number of Flare-ups With Soft Tissue Swelling and/or Cartilage Formation at Weeks 6 and 12 of Part A; and Week 12 of Part B
Timepoint [16] 0 0
Part A: Baseline and Weeks 6 and 12; and Part B: Baseline and Week 12
Secondary outcome [17] 0 0
Parts A and B: Duration of Active Symptomatic Flare-up
Timepoint [17] 0 0
Part A: From Baseline up to 36 months; and Part B: From Baseline up to 24 months
Secondary outcome [18] 0 0
Part B: Change From Baseline in Whole Body Burden of HO at Months 12 and 24
Timepoint [18] 0 0
Baseline and Months 12 and 24
Secondary outcome [19] 0 0
Part B: Mean Percentage of Flare-ups Per Participant-Month Overall
Timepoint [19] 0 0
From Baseline (Day 1) up to end of 2 year follow-up period, approximately a maximum of 96 months
Secondary outcome [20] 0 0
Part C: Mean Percentage of Flare-ups Per Participant-Month Overall
Timepoint [20] 0 0
From Baseline (Day 1) up to end of 2 year follow-up period, approximately a maximum of 96 months
Secondary outcome [21] 0 0
Part C: Percentage of Participants With New HO at Months 12, 24, 36, 60, and 72 (Last Visit)
Timepoint [21] 0 0
Months 12, 24, 36, 60, and 72 (last visit)

Eligibility
Key inclusion criteria
* Completion of Study PVO-1A-202/Part B.
* Written, signed, and dated informed consent and, for participants who are minors, age-appropriate participant 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 participants 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 females of childbearing potential (FOCBP) participants 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 participant or legally authorized representatives.
Minimum age
6 Years
Maximum age
65 Years
Sex
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 participant 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.
* 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.
* Participants 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
Completed
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)
NSW,QLD
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Queensland University of Technology (QUT) Institute of Health and Biomedical Innovation (IHBI) - Woolloongabba
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 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
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)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.