Exostoses, Multiple HereditaryPhase 2MO-PedNCT03442985
An Efficacy and Safety Study of Palovarotene for the Treatment of MO
A Phase 2 study testing Palovarotene 2.5 mg and Palovarotene 5.0 mg in people with Exostoses, Multiple Hereditary, run by Clementia Pharmaceuticals Inc. at 31 sites in 12 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 to 14 years
- Conditions the study is for
- Exostoses, Multiple Hereditary
- What is being tested?
- Palovarotene 2.5 mg and Palovarotene 5.0 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 193 participants
- Where
- 31 sitesin 12 countries
- Study dates
- 22 Mar 2018to 30 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
31 sites in 12 countries.
31 sites in 12 countries
United States13 sites
Johns Hopkins University
Baltimore, Maryland, 21205
Boston Children's Hospital
Boston, Massachusetts, 02115
Shriners Hospital for Children - Chicago
Chicago, Illinois, 60707
Memorial Hermann Hospital
Houston, Texas, 77030
Children's Orthopaedic Center
Los Angeles, California, 90027
The Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
Shriners Hospital for Children - Philadelphia
Philadelphia, Pennsylvania, 19410-4160
Shriners Hospitals for Children - Portland
Portland, Oregon, 97239
Mayo Clinic - PPDS
Rochester, Minnesota, 55905
Shriners Hospital for Children - Sacramento
Sacramento, California, 95817
University of California-San Francisco
San Francisco, California, 94158
Children's National Medical Center
Washington D.C., District of Columbia, 20010
The Paley Institute
West Palm Beach, Florida, 330407
Canada3 sites
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Shriners Hospital for Children - Canada
Montreal, Quebec, H4A 0A9
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
United Kingdom3 sites
Evelina London Children's Hospital
London, SE1 7EH
Royal Manchester Childrens Hospital
Manchester, M13 9WL
Royal National Orthopaedic Hospital
Stanmore, HA7 4LP
France2 sites
Hôpital universitaire Necker - Enfants Malades
Paris, 75015
Hôpital des Enfants, CHU de Toulouse
Toulouse, 31059
Japan2 sites
Nagoya University Hospital
Nagoya, Aiti, 4668560
Osaka University Hospital
Suita, Osaka, 565-0871
Turkey (Türkiye)2 sites
Ege University Medical Faculty Hospital
Bornova, İzmir
Bezmialem Vakif University Medical Faculty Hospital
Istanbul, 34093
Australia1 site
Westmead Children's Hospital
Westmead, New South Wales, 2145
About this study
Official title: 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).
Read the 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.
- Conditions
- Exostoses, Multiple Hereditary
- Being tested
- Palovarotene 2.5 mg, Palovarotene 5.0 mg, Placebo
- Keywords
- Multiple osteochondromas, Osteochondroma, Palovarotene, Hereditary multiple exostoses, HME, MO, Retinoic acid receptor gamma agonist, Retinoic acid receptor agonist
- Medical subject headings
- Exostoses, Multiple Hereditary, Osteochondroma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Palovarotene 2.5 mgDrug
Subjects received a weight-adjusted dose equivalent of 2.5 mg palovarotene, once daily, for up to 24 months.
Palovarotene 5.0 mgDrug
Subjects received a weight-adjusted dose equivalent of 5.0 mg palovarotene, once daily, for up to 24 months.
PlaceboOther
Subjects received placebo, once daily, for up to 24 months.
| Study group | Role | What they receive |
|---|---|---|
| Palovarotene 2.5 mg daily regimen | Experimental | Not described Receives: Drug: Palovarotene 2.5 mg |
| Palovarotene 5.0 mg daily regimen | Experimental | Not described Receives: Drug: Palovarotene 5.0 mg |
| Placebo regimen | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Month 12
Secondary outcomes (9)
Mean Change From Baseline in the Total Volume of New OCs at 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.
Measured: Baseline (Day 1) and Month 12
Percentage of Participants With No New OCs
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.
Measured: Month 12
Annualized Rate of New or Worsening Deformities
The annualized rate of new or worsening deformities as assessed by radiographic imaging of both upper and lower limbs.
Measured: Month 12
Annualized Rate of MO-Related Surgeries
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.
Measured: Month 12
Maximum Observed Plasma Drug Concentrations at Steady State (Cmax,ss) of Palovarotene
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Month 1: pre-dose and 3, 6, 10 and 24 hours post-dose
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
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.
Measured: Day 1 and Month 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start22 Mar 2018
- Primary completion24 Mar 2020
- Study completion30 Oct 2020
Why it stopped: Trial was terminated early to analyze the accumulated data and evaluate the efficacy, safety and future of palovarotene in MO.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Exostoses, Multiple HereditaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, randomized, double-blind, placebo-controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 193 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clementia Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03442985
- Sponsor's protocol ID
- PVO-2A-201
- Other IDs
- 2017-002751-28, 2017
- Acronym
- MO-Ped
- Status last verified
- Jul 2022
- First submitted
- 11 Oct 2017
- Last updated
- 1 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29120519Sangiorgi 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.
PubMed 41188357
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Palovarotene in Subjects With Multiple Osteochondromas
- ClinicalTrials.gov ID
- NCT03442985
- Acronym / sponsor ID
- MO-Ped / PVO-2A-201
- Conditions
- Exostoses, Multiple Hereditary
- Keywords
- Multiple osteochondromas, Osteochondroma, Palovarotene, Hereditary multiple exostoses, HME, MO, Retinoic acid receptor gamma agonist, Retinoic acid receptor agonist
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Trial was terminated early to analyze the accumulated data and evaluate the efficacy, safety and future of palovarotene in MO.
- Enrolment
- 193 participants (actual)
- Lead sponsor
- Clementia Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Mar 2018 (actual)
- Primary completion
- 24 Mar 2020 (actual)
- Study completion
- 30 Oct 2020 (actual)
- First posted
- 22 Feb 2018 (actual)
- Results
- Posted 1 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Multicenter, randomized, double-blind, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 2 to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Palovarotene 2.5 mgSubjects received a weight-adjusted dose equivalent of 2.5 mg palovarotene, once daily, for up to 24 months. | Drug | Palovarotene 2.5 mg daily regimen |
| Palovarotene 5.0 mgSubjects received a weight-adjusted dose equivalent of 5.0 mg palovarotene, once daily, for up to 24 months. | Drug | Palovarotene 5.0 mg daily regimen |
| PlaceboSubjects received placebo, once daily, for up to 24 months. | Other | Placebo regimen |
Primary outcome
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).
9 secondary outcomes
Mean Change From Baseline in the Total Volume of New OCs at Month 12
Time frame: Baseline (Day 1) and Month 12
Percentage of Participants With No New OCs
Time frame: Month 12
Annualized Rate of New or Worsening Deformities
Time frame: Month 12
Annualized Rate of MO-Related Surgeries
Time frame: 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
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
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
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
Number of Participants With Palatability of Sprinkled Palovarotene and Placebo
Time frame: Day 1 and Month 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29120519Inubushi 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.
- Derived from this study: PubMed 41188357Sangiorgi 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.
- MHE CoalitionLink provided by the sponsor.
- MHE Research FoundationLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ipsen Medical Director study director
Ipsen
31 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Palovarotene 2.5 mg and Palovarotene 5.0 mg in people with Exostoses, Multiple Hereditary, run by Clementia Pharmaceuticals Inc. at 31 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States, Canada, United Kingdom, France, Japan and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annualized Rate of New Osteochondromas (OCs) (time frame: Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03442985, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2022.