NCT03312634

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
107

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_3

Geographic Reach
11 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 9, 2017

Completed
9 days until next milestone

First Posted

Study publicly available on registry

October 18, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

November 30, 2017

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 24, 2020

Completed
2.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 7, 2022

Completed
6 months until next milestone

Results Posted

Study results publicly available

March 14, 2023

Completed
Last Updated

November 29, 2023

Status Verified

November 1, 2023

Enrollment Period

2.2 years

First QC Date

October 9, 2017

Results QC Date

January 20, 2023

Last Update Submit

November 28, 2023

Conditions

Fibrodysplasia Ossificans Progressiva

Keywords

Interventional studyClinical trial phase 3Efficacy and safetyHeterotopic ossificationFlare-upPalovaroteneRetinoic acid receptor agonistRetinoic acid receptor gamma agonistClementiaMyositis Ossificans ProgressivaMunchmeyer's DiseaseFOPFOP variants

Outcome Measures

Primary Outcomes (1)

  • Annualized New Heterotopic Ossification (HO)

    The annualized new HO was assessed by low-dose, whole body computed tomography (WBCT), excluding head. The weighted linear mixed effect method without square-root transformation and negatives included was used for annualized new HO analysis.

    Baseline (within one month of screening/Day 1) and up to 24 months

Secondary Outcomes (4)

  • Percentage of Participants With Any New HO

    From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)

  • Number of Body Regions With New HO

    From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)

  • Percentage of Participants With Flare-Ups

    Month 12

  • Ratio of Flare-Up Per Participant-Month of Exposure

    From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)

Study Arms (1)

Palovarotene Chronic/Flare-Up Regimen

EXPERIMENTAL

Participants received 5 mg palovarotene once daily for up to 48 months; and 20 mg palovarotene once daily for 28 days, followed by 10 mg for 56 days for flareups. (Dosing was adjusted for weight in skeletally immature subjects.)

Drug: Palovarotene

Interventions

PalovaroteneDRUG

Palovarotene was taken orally once daily at approximately the same time each day following a meal.

Palovarotene Chronic/Flare-Up Regimen

Eligibility Criteria

Age4 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Written, signed, and dated informed subject/parent consent; and for subjects who are minors, age-appropriate assent (performed according to local regulations).
  • Males or females at least 4 years of age.
  • No flare-up symptoms within the past 4 weeks, including at the time of enrollment.
  • Abstinent or using two highly effective forms of birth control.
  • Accessible for treatment and follow-up; able to undergo all study procedures including low-dose WBCT (excluding head) without sedation.

You may not qualify if:

  • Weight \<10 kg.
  • Concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.
  • Amylase or lipase \>2x above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
  • Elevated aspartate aminotransferase or alanine aminotransferase \>2.5x ULN.
  • Fasting triglycerides \>400 mg/dL with or without therapy.
  • Female subjects who are breastfeeding.
  • Subjects with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.
  • Simultaneous participation in another clinical research study (other than palovarotene studies) within 4 weeks prior to Screening; or within five half-lives of the investigational agent, whichever is longer.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

University of California San Francisco, Division of Endocrinology and Metabolism

San Francisco, California, 94143, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania, Internal Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Hospital Italiano de Buenos Aires, Tte General Juan Domingo Peron 4190

Buenos Aires, C1199ACH, Argentina

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Queensland University of Technology

Woolloongabba, Queensland, 4102, Australia

Location

Hospital Israelita Albert Einstein

São Paulo, São Paulo, 05652-900, Brazil

Location

Hospital for Sick Children, 555 University Avenue

Toronto, Ontario, M5G 1X8, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Groupe Hospitalier Necker Enfants Malades

Paris, 75015, France

Location

Istituto Giannina Gaslini

Genoa, Liguria, 16147, Italy

Location

The University of Tokyo Hospital

Tokyo, Bunkyo-ku, 113-8655, Japan

Location

Hospital Universitari i Politècnic La Fe, Unidad de Reumatología Pediatrica

Valencia, Avinguda de Fernando Abril Martorell, Nº 106, 46026, Spain

Location

Norrlands Universitetssjukhus

Umeå, SE-90185, Sweden

Location

Royal National Orthopaedic Hospital, Brockely Hill

Stanmore, HA7 4LP, United Kingdom

Location

Related Publications (3)

  • 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-gamma agonists. Nat Med. 2011 Apr;17(4):454-60. doi: 10.1038/nm.2334. Epub 2011 Apr 3.

    PMID: 21460849BACKGROUND

  • Lindborg CM, Al Mukaddam M, Baujat G, Cho TJ, De Cunto CL, Delai PLR, Eekhoff EMW, Haga N, Hsiao EC, Morhart R, de Ruiter R, Scott C, Seemann P, Szczepanek M, Tabarkiewicz J, Pignolo RJ, Kaplan FS. Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility. Clin Orthop Relat Res. 2023 Dec 1;481(12):2447-2458. doi: 10.1097/CORR.0000000000002672. Epub 2023 May 8.

    PMID: 37156007DERIVED

  • Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Brown MA, Cheung AM, De Cunto C, Delai P, Haga N, Kannu P, Keen R, Le Quan Sang KH, Mancilla EE, Marino R, Strahs A, Kaplan FS. Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP). J Bone Miner Res. 2023 Mar;38(3):381-394. doi: 10.1002/jbmr.4762. Epub 2023 Jan 25.

    PMID: 36583535DERIVED

Related Links

MeSH Terms

Conditions

Myositis OssificansOssification, Heterotopic

Interventions

Palovarotene

Condition Hierarchy (Ancestors)

MyositisMuscular DiseasesMusculoskeletal DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Limitations and Caveats

A valid comparison of AEs from observational study (PVO-1A-001) was not made since AEs were only captured as related to study procedures.

Results Point of Contact

Title
Medical Director
Organization
Ipsen
clinical.trials@ipsen.com
see email

Study Officials

  • Ipsen Medical Director

    Ipsen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: A multicenter, open-label study. NHS data (study PVO-1A-001) will be used as an external control in the analysis.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 9, 2017

First Posted

October 18, 2017

Study Start

November 30, 2017

Primary Completion

January 24, 2020

Study Completion

September 7, 2022

Last Updated

November 29, 2023

Results First Posted

March 14, 2023

Record last verified: 2023-11

Locations

IT(1)FR(1)GB(1)AR(1)CA(2)AU(2)US(4)BR(1)JP(1)ES(1)SE(1)