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Trial record 4 of 7 for:    clementia

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

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ClinicalTrials.gov Identifier: NCT03442985
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Clementia Pharmaceuticals Inc.

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).

Condition or disease Intervention/treatment Phase
Exostoses, Multiple Hereditary Drug: Palovarotene 2.5 mg Drug: Palovarotene 5.0 mg Other: Placebo Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
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
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Palovarotene in Subjects With Multiple Osteochondromas
Actual Study Start Date : April 20, 2018
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : February 2021


Arm Intervention/treatment
Experimental: Palovarotene 2.5 mg daily regimen 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.

Experimental: Palovarotene 5.0 mg daily regimen 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.

Placebo Comparator: Placebo regimen Other: Placebo
Subjects will receive placebo, once daily, for up to 24 months.




Primary Outcome Measures :
  1. Annualized rate of new osteochondromas [ Time Frame: Month 24 ]
    The annualized rate of new osteochondromas as assessed by whole body magnetic resonance imaging (MRI).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Palovarotene area under the concentration-time curve (AUC) [ Time Frame: Month 1 ]
    Determination of AUC at steady-state assessed during treatment.

  5. 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.


Other Outcome Measures:
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. FPS-R [ Time Frame: Months 6, 12, 18, and 24/EOT ]
    The Faces Pain Scale - Revised (FPS-R) to assess pain intensity.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03442985


Contacts
Contact: Clementia Call Center (US/Canada Only) 1-800-750-8710 ClinicalTrials@clementiapharma.com

Locations
United States, California
Children's Orthopaedic Center Recruiting
Los Angeles, California, United States, 90027
Contact: Regina Woon    323-361-2843    rwoon@chla.usc.edu   
Principal Investigator: Vernon T Tolo, MD         
Sub-Investigator: Rachel Y Goldstein, MD, MPH         
University of California-San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Emma Canepa    415-502-2425    Emma.Canepa@ucsf.edu   
Principal Investigator: Jessica Tenney, MD         
Sub-Investigator: Edward Hsiao, MD         
Sub-Investigator: Janet Lee, MD         
United States, Florida
Paley Orthopedic and Spine Institute Recruiting
West Palm Beach, Florida, United States, 330407
Contact: Troy Rand    561-531-1553    trand@paleyinstitute.org   
Principal Investigator: David Feldman, MD         
United States, Illinois
Shriners Hospital for Children - Chicago Recruiting
Chicago, Illinois, United States, 60707
Contact: Sahar Hassani, MS    773-622-5400    shassani@shrinenet.org   
Principal Investigator: Jeffrey Ackman, MD         
Sub-Investigator: Haluk Altiok, MD         
Sub-Investigator: Purnendu Gupta, MD         
Sub-Investigator: Peter Smith, MD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Andrea Hale    167-135-5600    Andrea.Hale@childrens.harvard.edu   
Principal Investigator: Christina Jacobsen, MD         
Sub-Investigator: Ingrid Holm, MD, MPH         
Sub-Investigator: Samantha Spencer, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia (CHOP) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Vashisht Arshanapally, BS    267-426-7482    arshanapav@email.chop.edu   
Principal Investigator: Michael A Levine, MD         
Sub-Investigator: Edna Mancilla, MD         
Shriners Hospital for Children - Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19410-4160
Contact: Jamie Landgarten, MS    215-430-4239    jlandgarten@shrinenet.org   
Principal Investigator: Bethany Lipa, MD         
United States, Texas
Memorial Hermann Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Mayank Rao    713-704-2639    Mayank.Rao@uth.tmc.edu   
Principal Investigator: Ernest Conrad, MD         
Sub-Investigator: Shiraz Younas, MD         
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Tony (Yongyao) Tan    (416) 813-7654 ext 203575    tony.tan@sickkids.ca   
Principal Investigator: Roberto Mendoza-Londono, MD         
Sub-Investigator: Lucie Dupuis, MD         
Sub-Investigator: Andrew Howard, MD         
Sub-Investigator: Jennifer Stimec, MD         
Sub-Investigator: Irene Lara-Corrales, MD         
Sub-Investigator: Peter Kannu, MD         
Japan
Nagoya University Hospital Recruiting
Nagoya, Aichi, Japan
Contact: Kumiko Tsukamoto    +81-52-561-0166    kumiko-tsukamoto@irom.co.jp   
Principal Investigator: Hiroshi Kitoh, MD         
Sub-Investigator: Kenichi Mishima, MD         
Sub-Investigator: Tadashi Nagata, MD         
Sub-Investigator: Masaki Matsushita, MD         
Osaka University Hospital Recruiting
Suita, Osaka, Japan, 565-0871
Contact: Hiromi Tanaka (SC)    +81662108290    h-tanaka@dmi.med.osaka-u.ac.jp   
Principal Investigator: Keiichi Ozono, MD, PhD         
Sub-Investigator: Taichi Kitaoka, MD         
Sub-Investigator: Hiroyuki Saitou, MD         
Sub-Investigator: Dr. Kiyoshi Yoshida         
Sub-Investigator: Dr. Hidetatsu Otani         
Sub-Investigator: Dr. Kenichiro Hamada         
Sub-Investigator: Dr. Satoshi Takenaka         
Sub-Investigator: Hiroto Takahashi, MD         
Sponsors and Collaborators
Clementia Pharmaceuticals Inc.

Additional Information:
Publications:
Responsible Party: Clementia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03442985     History of Changes
Other Study ID Numbers: PVO-2A-201
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Clementia Pharmaceuticals Inc.:
Multiple osteochondromas
Osteochondroma
Palovarotene
Hereditary multiple exostoses
HME
MO
Retinoic acid receptor gamma agonist
Retinoic acid receptor agonist

Additional relevant MeSH terms:
Exostoses
Osteophyte
Osteochondroma
Exostoses, Multiple Hereditary
Osteochondromatosis
Hyperostosis
Bone Diseases
Musculoskeletal Diseases
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteochondrodysplasias
Bone Diseases, Developmental
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn