An Efficacy and Safety Study of Palovarotene for the Treatment of MO (MO-Ped)

July 7, 2022 updated by: Clementia Pharmaceuticals Inc.

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Palovarotene in Subjects With Multiple Osteochondromas

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Multiple osteochondromas is a rare condition where children develop multiple benign cartilage-capped bony tumors called osteochondromas on bones throughout the body, resulting in pain, deformity, limb length discrepancy, disability, and eventually arthritis and possible malignancy. The primary objective is to compare the efficacy of two dosage regimens of palovarotene with placebo to prevent the formation of new osteochondromas in pediatric MO subjects with exostosin 1 or exostosin 2 gene mutations. Osteochondroma formation was assessed by whole body magnetic resonance imaging (MRI). Secondary efficacy objectives were to compare the effects of palovarotene with placebo on the volume of osteochondromas as assessed by MRI; the proportion of subjects with no new osteochondromas as assessed by whole-body MRI; the annualized rate of new or worsening deformities; the annualized rate of MO-related surgeries; and palatability. The overall safety and pharmacokinetics of palovarotene and the effects of palovarotene on linear growth, bone growth plates, bone mineral density, quality of life, and pain due to osteochondromas was also studied.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
193

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Westmead Children's Hospital
  • Belgium
    • Antwerp
      • Edegem, Antwerp, Belgium, 2650
        • UZ Antwerpen
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montréal, Quebec, Canada, H3T 1C5
        • Centre Hospitalier Universitaire Sainte-Justine
      • Montréal, Quebec, Canada, H4A 0A9
        • Shriners Hospital for Children - Canada
  • France
      • Paris, France, 75015
        • Hôpital Universitaire Necker - Enfants Malades
      • Toulouse, France, 31059
        • Hopital des Enfants, CHU de Toulouse
  • Italy
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40136
        • Istituti Ortopedici Rizzoli
  • Japan
    • Aiti
      • Nagoya, Aiti, Japan, 4668560
        • Nagoya University Hospital
    • Osaka
      • Suita, Osaka, Japan, 565-0871
        • Osaka University Hospital
  • Netherlands
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1091 AC
        • OLVG locatie Oost
  • Portugal
      • Coimbra, Portugal, 3000-602
        • Hospital Pediátrico de Coimbra
  • Spain
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
  • Turkey
      • Istanbul, Turkey, 34093
        • Bezmialem Vakif University Medical Faculty Hospital
    • Izmir
      • Bornova, Izmir, Turkey
        • Ege University Medical Faculty Hospital
  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • Evelina London Children's Hospital
      • Manchester, United Kingdom, M13 9WL
        • Royal Manchester Childrens Hospital
      • Stanmore, United Kingdom, HA7 4LP
        • Royal National Orthopaedic Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Children's Orthopaedic Center
      • Sacramento, California, United States, 95817
        • Shriners Hospital for Children - Sacramento
      • San Francisco, California, United States, 94158
        • University of California-San Francisco
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • West Palm Beach, Florida, United States, 330407
        • The Paley Institute
    • Illinois
      • Chicago, Illinois, United States, 60707
        • Shriners Hospital for Children - Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - PPDS
    • Oregon
      • Portland, Oregon, United States, 97239
        • Shriners Hospitals for Children - Portland
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia (CHOP)
      • Philadelphia, Pennsylvania, United States, 19410-4160
        • Shriners Hospital for Children - Philadelphia
    • Texas
      • Houston, Texas, United States, 77030
        • Memorial Hermann Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 10 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Palovarotene 2.5 mg daily regimen
Drug: Palovarotene 2.5 mg
Subjects received a weight-adjusted dose equivalent of 2.5 mg palovarotene, once daily, for up to 24 months.
Experimental: Palovarotene 5.0 mg daily regimen
Drug: Palovarotene 5.0 mg
Subjects received a weight-adjusted dose equivalent of 5.0 mg palovarotene, once daily, for up to 24 months.
Placebo Comparator: Placebo regimen
Other: Placebo
Subjects received placebo, once daily, for up to 24 months.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Annualized Rate of New Osteochondromas (OCs)
Time Frame: Month 12
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in the Total Volume of New OCs at Month 12
Time Frame: Baseline (Day 1) and Month 12
The change from baseline in the total volume of OCs was assessed by whole-body MRI. Baseline was defined as the last available value prior to first administration of study drug.
Baseline (Day 1) and Month 12
Percentage of Participants With No New OCs
Time Frame: Month 12
The percentage of participants with no new OCs as assessed by whole-body MRI. Participants with new OCs not identified by MRI due to surgical resection during the treatment period were categorized as having new OCs for this analysis.
Month 12
Annualized Rate of New or Worsening Deformities
Time Frame: Month 12
The annualized rate of new or worsening deformities as assessed by radiographic imaging of both upper and lower limbs.
Month 12
Annualized Rate of MO-Related Surgeries
Time Frame: Month 12
The MO-related surgeries included any procedure indicated for the treatment of MO, such as an excision of a symptomatic OC or correction of a limb deformity.
Month 12
Maximum Observed Plasma Drug Concentrations at Steady State (Cmax,ss) of Palovarotene
Time Frame: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
The Cmax,ss of palovarotene was evaluated. The pharmacokinetic (PK) sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
Minimum Observed Plasma Drug Concentrations at Steady State (Cmin,ss) of Palovarotene
Time Frame: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
The Cmin,ss of palovarotene was evaluated. The PK sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
Time to Maximum Observed Drug Concentration at Steady State (Tmax,ss) of Palovarotene
Time Frame: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
The Tmax,ss of palovarotene was evaluated. The PK sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
Area Under the Plasma Concentration-Time Curve at Steady State From Time 0 to 24 Hours After Dosing (AUC0-24,ss) of Palovarotene
Time Frame: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
The AUC0-24,ss of palovarotene was evaluated. The PK sampling was performed at Month 1. If samples could not be obtained at Month 1, then one additional attempt was made at a subsequent visit.
Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Time Frame: Day 1 and Month 1
Palatability of palovarotene and placebo when sprinkled on specific foods as assessed with a 5-point hedonic face scale at the first dose (Day 1) and at Month 1 in all participants (including <4 years old) who sprinkled the palovarotene or placebo onto a spoonful of specific foods. The hedonic face scale ranges from 1 to 5 where, 1= dislike very much, 2= dislike slightly, 3= neither like nor dislike, 4= like slightly, 5= like very much. Higher scores indicate positive outcome.
Day 1 and Month 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Clementia Pharmaceuticals Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 22, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 24, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 22, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 1, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PVO-2A-201
  • 2017-002751-28 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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