An Efficacy and Safety Study of Palovarotene for the Treatment of MO

NCT03442985 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: PVO-2A-2012017-002751-28
• Study Type: interventional
• Target: 193
• Locations: 12 countries
• Sites: 31

Brief Summary

This is a randomized, double-blind, placebo-controlled study comparing the safety and efficacy of 2 dosage regimens of palovarotene versus placebo in preventing disease progression in pediatric subjects with multiple osteochondromas (MO).

Conditions

Exostoses, Multiple Hereditary

Keywords

Multiple osteochondromas; Osteochondroma; Palovarotene; Hereditary multiple exostoses; HME; MO; Retinoic acid receptor gamma agonist; Retinoic acid receptor agonist

Outcome Measures

Primary Outcomes (1)

• Annualized Rate of New Osteochondromas (OCs)

  The annualized rate of new OCs was assessed by whole-body magnetic resonance imaging (MRI) (that is, the total number of new OCs divided by the time in years between the baseline and latest post-baseline MRI).

  Month 12

Secondary Outcomes (9)

• Mean Change From Baseline in the Total Volume of New OCs at Month 12

  Baseline (Day 1) and Month 12

• Percentage of Participants With No New OCs

  Month 12

• Annualized Rate of New or Worsening Deformities

  Month 12

• Annualized Rate of MO-Related Surgeries

  Month 12

• Maximum Observed Plasma Drug Concentrations at Steady State (Cmax,ss) of Palovarotene

  Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose

Study Arms (3)

Palovarotene 2.5 mg daily regimen

EXPERIMENTAL

Drug: Palovarotene 2.5 mg

Palovarotene 5.0 mg daily regimen

EXPERIMENTAL

Drug: Palovarotene 5.0 mg

Placebo regimen

PLACEBO COMPARATOR

Other: Placebo

Interventions

Palovarotene 2.5 mg DRUG

Subjects received a weight-adjusted dose equivalent of 2.5 mg palovarotene, once daily, for up to 24 months.

Palovarotene 2.5 mg daily regimen

Palovarotene 5.0 mg DRUG

Subjects received a weight-adjusted dose equivalent of 5.0 mg palovarotene, once daily, for up to 24 months.

Palovarotene 5.0 mg daily regimen

Placebo OTHER

Subjects received placebo, once daily, for up to 24 months.

Placebo regimen

Eligibility Criteria

• Age: 2 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written, signed, and dated informed subject/parent consent and age-appropriate assent (performed according to local regulations).
• A clinical diagnosis of MO with disease-causing exostosin 1 or 2 gene mutations.
• Male or female from 2 to 14 years of age.
• Female subjects must be premenarchal at screening.
• A bone age at screening of 14 years or less.
• Symptomatic MO, defined as five or more clinically evident osteochondromas and a new or enlarged osteochondroma that occurred in the preceding 12 months, five or more clinically evident osteochondromas and the presence of a painful osteochondroma, a skeletal deformity, a joint limitation, or prior surgery for a MO-related complication.
• The ability to undergo whole body MRI with or without sedation/general anesthesia.
• Use of two effective methods of birth control during treatment, and for 1 month after treatment discontinuation, unless committed to true abstinence from heterosexual sex. Sexually active females of child-bearing potential must also agree to start effective methods of birth control at screening.

You may not qualify if:

• Weight under 10 kg.
• Other syndromic conditions such as Langer-Giedion or Potocki-Shaffer.
• Any subject with neurologic signs suggestive of spinal cord impingement.
• Concomitant medications that are strong inhibitors or inducers of cytochrome P450 3A4 activity.
• Amylase or lipase \>2 times the above the upper limit of normal (\>2×ULN) or with a history of chronic pancreatitis.
• Elevated aspartate aminotransferase or alanine aminotransferase above 2.5×ULN.
• Any surgical implant that is contraindicated for MRI.

Sponsors & Collaborators

• Clementia Pharmaceuticals Inc.: lead

Study Sites (31)

Children's Orthopaedic Center

Los Angeles, California, 90027, United States

Location

Shriners Hospital for Children - Sacramento

Sacramento, California, 95817, United States

Location

University of California-San Francisco

San Francisco, California, 94158, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

The Paley Institute

West Palm Beach, Florida, 330407, United States

Location

Shriners Hospital for Children - Chicago

Chicago, Illinois, 60707, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

Shriners Hospitals for Children - Portland

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

Shriners Hospital for Children - Philadelphia

Philadelphia, Pennsylvania, 19410-4160, United States

Location

Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

Westmead Children's Hospital

Westmead, New South Wales, 2145, Australia

Location

UZ Antwerpen

Edegem, Antwerp, 2650, Belgium

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Shriners Hospital for Children - Canada

Montreal, Quebec, H4A 0A9, Canada

Location

Hôpital universitaire Necker - Enfants Malades

Paris, 75015, France

Location

Hôpital des Enfants, CHU de Toulouse

Toulouse, 31059, France

Location

Istituti Ortopedici Rizzoli

Bologna, Emilia-Romagna, 40136, Italy

Location

Nagoya University Hospital

Nagoya, Aiti, 4668560, Japan

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

OLVG locatie Oost

Amsterdam, North Holland, 1091 AC, Netherlands

Location

Hospital Pediátrico de Coimbra

Coimbra, 3000-602, Portugal

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Ege University Medical Faculty Hospital

Bornova, İzmir, Turkey (Türkiye)

Location

Bezmialem Vakif University Medical Faculty Hospital

Istanbul, 34093, Turkey (Türkiye)

Location

Evelina London Children's Hospital

London, SE1 7EH, United Kingdom

Location

Royal Manchester Childrens Hospital

Manchester, M13 9WL, United Kingdom

Location

Royal National Orthopaedic Hospital

Stanmore, HA7 4LP, United Kingdom

Location

Related Publications (2)

• Inubushi T, Lemire I, Irie F, Yamaguchi Y. Palovarotene Inhibits Osteochondroma Formation in a Mouse Model of Multiple Hereditary Exostoses. J Bone Miner Res. 2018 Apr;33(4):658-666. doi: 10.1002/jbmr.3341. Epub 2017 Nov 30.

  PMID: 29120519 BACKGROUND

• Sangiorgi L, Conrad EU, Shih F, Strahs A, Feldman DS. Palovarotene for patients with multiple hereditary exostosis: results of MO-Ped, a terminated, randomized, placebo-controlled, double-blind phase 2 trial. Sci Rep. 2025 Nov 4;15(1):38563. doi: 10.1038/s41598-025-22554-6.

  PMID: 41188357 DERIVED

Related Links

• MHE Coalition
• MHE Research Foundation

MeSH Terms

Conditions

Exostoses, Multiple Hereditary; Osteochondroma

Interventions

Palovarotene

Condition Hierarchy (Ancestors)

Osteochondromatosis; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Exostoses; Hyperostosis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

The Sponsor terminated the study early due to a partial clinical hold instituted by the Food and Drug Administration. Recruitment was stopped before full enrollment was reached, and study drug administration was discontinued.

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
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, randomized, double-blind, placebo-controlled

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: February 22, 2018
• Study Start: March 22, 2018
• Primary Completion: March 24, 2020
• Study Completion: October 30, 2020
• Last Updated: August 1, 2022
• Results First Posted: August 1, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); PT (1); AU (1); US (13); JP (2); ES (1); GB (3); TU (2); FR (2); NL (1); CA (3); BE (1)