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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03442985
Recruitment Status : Active, not recruiting
First Posted : February 22, 2018
Last Update Posted : April 30, 2020
Sponsor:
Information provided by (Responsible Party):
Ipsen ( Clementia Pharmaceuticals Inc. )

Tracking Information
First Submitted Date  ICMJE October 11, 2017
First Posted Date  ICMJE February 22, 2018
Last Update Posted Date April 30, 2020
Actual Study Start Date  ICMJE April 20, 2018
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
Annualized rate of new osteochondromas [ Time Frame: Month 24 ]
The annualized rate of new osteochondromas as assessed by whole body magnetic resonance imaging (MRI).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
  • Total volume of osteochondromas [ Time Frame: Months 12 and 24/end-of-treatment (EOT) ]
    The change from baseline in the total volume of osteochondromas as assessed by whole body MRI.
  • Annualized rate of new or worsening deformities [ Time Frame: Months 12 and 24/EOT ]
    The annualized rate of new or worsening deformities as assessed by radiographic imaging of both upper and lower limbs.
  • Annualized rate of MO-related surgeries [ Time Frame: Months 12 and 24/EOT ]
    The annualized rate of MO-related surgeries. Surgeries include surgical excisions of a symptomatic osteochondroma and surgical procedures to correct a joint deformities or functional limitations.
  • Palovarotene area under the concentration-time curve (AUC) [ Time Frame: Month 1 ]
    Determination of AUC at steady-state assessed during treatment.
  • Palatability [ Time Frame: Day 1 and Month 1 ]
    The palatability of the drug product versus placebo when sprinkled onto specific foods as assessed by a five-point hedonic face scale.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
  • Total volume of osteochondromas [ Time Frame: Months 12 and 24/end-of-treatment (EOT) ]
    The change from baseline in the total volume of osteochondromas as assessed by whole body MRI.
  • Annualized rate of new or worsening deformities [ Time Frame: Months 12 and 24/EOT ]
    The annualized rate of new or worsening deformities as assessed by radiographic imaging of both upper and lower limbs.
  • Annualized rate of MO-related surgeries [ Time Frame: Months 12 and 24/EOT ]
    The annualized rate of MO-related surgeries. Surgeries include surgical excisions of a symptomatic osteochondroma and surgical procedures to correct a joint deformities or functional limitations.
  • Palovarotene area under the concentration-time curve (AUC) [ Time Frame: Month 1 ]
    Determination of AUC at steady-state assessed during treatment.
Current Other Pre-specified Outcome Measures
 (submitted: October 17, 2018)
  • Safety of Palovarotene: Monitoring of adverse events [ Time Frame: Study Day 1; and from Months 1 to 30/ET at every subject contact ]
    Monitoring of adverse events.
  • Volume of osteochondroma cartilage cap [ Time Frame: Months 12 and 24 ]
    Change from baseline in the total volume of cartilage cap of osteochondromas as assessed by whole body MRI
  • Annualized rate of new or worsening functional limitations [ Time Frame: Months 12 and 24/EOT ]
    The annualized rate of new or worsening functional limitations. Functional limitations are defined as restrictions in joint range of motion.
  • PedsQL [ Time Frame: Months 6, 12, 18, and 24/EOT ]
    The Pediatric Quality of Life Inventory (PedsQL, version 4.0) questionnaire to assess quality of life.
  • PROMIS Global Health Scale [ Time Frame: Months 6, 12, 18, and 24/EOT ]
    The Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference pediatric item bank to assess the effect of pain on daily activities.
  • FPS-R [ Time Frame: Months 6, 12, 18, and 24/EOT ]
    The Faces Pain Scale - Revised (FPS-R) to assess pain intensity.
Original Other Pre-specified Outcome Measures
 (submitted: February 21, 2018)
  • Safety of Palovarotene: Monitoring of adverse events [ Time Frame: Study Day 1; and from Months 1 to 36/ET at every subject contact ]
    Monitoring of adverse events.
  • Annualized rate of new or worsening functional limitations [ Time Frame: Months 12 and 24/EOT ]
    The annualized rate of new or worsening functional limitations. Functional limitations are defined as restrictions in joint range of motion.
  • PedsQL [ Time Frame: Months 6, 12, 18, and 24/EOT ]
    The Pediatric Quality of Life Inventory (PedsQL, version 4.0) questionnaire to assess quality of life.
  • PROMIS Global Health Scale [ Time Frame: Months 6, 12, 18, and 24/EOT ]
    The Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference pediatric item bank to assess the effect of pain on daily activities.
  • FPS-R [ Time Frame: Months 6, 12, 18, and 24/EOT ]
    The Faces Pain Scale - Revised (FPS-R) to assess pain intensity.
 
Descriptive Information
Brief Title  ICMJE An Efficacy and Safety Study of Palovarotene for the Treatment of MO
Official Title  ICMJE A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Palovarotene in Subjects With Multiple Osteochondromas
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).
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 will be assessed by whole body magnetic resonance imaging (MRI). Secondary efficacy objectives are to compare the effect of palovarotene on the volume of osteochondromas as assessed by MRI; and on the annualized rate of new or worsening deformities and MO-related surgeries. The overall safety of palovarotene and the effects of palovarotene on linear growth, bone growth plates, bone mineral density, quality of life, and pain due to osteochondromas will also be studied.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Multicenter, randomized, double-blind, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Exostoses, Multiple Hereditary
Intervention  ICMJE
  • Drug: Palovarotene 2.5 mg
    Subjects will receive a weight-adjusted dose equivalent of 2.5 mg palovarotene, once daily, for up to 24 months.
  • Drug: Palovarotene 5.0 mg
    Subjects will receive a weight-adjusted dose equivalent of 5.0 mg palovarotene, once daily, for up to 24 months.
  • Other: Placebo
    Subjects will receive placebo, once daily, for up to 24 months.
Study Arms  ICMJE
  • Experimental: Palovarotene 2.5 mg daily regimen
    Intervention: Drug: Palovarotene 2.5 mg
  • Experimental: Palovarotene 5.0 mg daily regimen
    Intervention: Drug: Palovarotene 5.0 mg
  • Placebo Comparator: Placebo regimen
    Intervention: Other: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 29, 2020)
194
Original Estimated Enrollment  ICMJE
 (submitted: February 21, 2018)
240
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 14 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Italy,   Japan,   Netherlands,   Portugal,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03442985
Other Study ID Numbers  ICMJE PVO-2A-201
2017-002751-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ipsen ( Clementia Pharmaceuticals Inc. )
Study Sponsor  ICMJE Clementia Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ipsen Medical Director Ipsen
PRS Account Ipsen
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP