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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03442985




Registration number
NCT03442985
Ethics application status
Date submitted
11/10/2017
Date registered
22/02/2018
Date last updated
3/07/2019

Titles & IDs
Public title
An Efficacy and Safety Study of Palovarotene for the Treatment of MO
Scientific title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Palovarotene in Subjects With Multiple Osteochondromas
Secondary ID [1] 0 0
PVO-2A-201
Universal Trial Number (UTN)
Trial acronym
MO-Ped
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Exostoses, Multiple Hereditary 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Palovarotene 2.5 mg
Treatment: Drugs - Palovarotene 5.0 mg
Other interventions - Placebo

Experimental: Palovarotene 2.5 mg daily regimen -

Experimental: Palovarotene 5.0 mg daily regimen -

Placebo Comparator: Placebo regimen -


Treatment: Drugs: Palovarotene 2.5 mg
Subjects will receive a weight-adjusted dose equivalent of 2.5 mg palovarotene, once daily, for up to 24 months.

Treatment: Drugs: 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 interventions: Placebo
Subjects will receive placebo, once daily, for up to 24 months.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized rate of new osteochondromas - The annualized rate of new osteochondromas as assessed by whole body magnetic resonance imaging (MRI).
Timepoint [1] 0 0
Month 24
Secondary outcome [1] 0 0
Total volume of osteochondromas - The change from baseline in the total volume of osteochondromas as assessed by whole body MRI.
Timepoint [1] 0 0
Months 12 and 24/end-of-treatment (EOT)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Months 12 and 24/EOT
Secondary outcome [3] 0 0
Annualized rate of MO-related surgeries - 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.
Timepoint [3] 0 0
Months 12 and 24/EOT
Secondary outcome [4] 0 0
Palovarotene area under the concentration-time curve (AUC) - Determination of AUC at steady-state assessed during treatment.
Timepoint [4] 0 0
Month 1
Secondary outcome [5] 0 0
Palatability - The palatability of the drug product versus placebo when sprinkled onto specific foods as assessed by a five-point hedonic face scale.
Timepoint [5] 0 0
Day 1 and Month 1

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
2 Years
Maximum age
14 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Children's Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Belgium
State/province [11] 0 0
Antwerp
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
France
State/province [15] 0 0
Toulouse
Country [16] 0 0
Japan
State/province [16] 0 0
Aichi
Country [17] 0 0
Japan
State/province [17] 0 0
Osaka
Country [18] 0 0
Netherlands
State/province [18] 0 0
Noord-Holland
Country [19] 0 0
Portugal
State/province [19] 0 0
Coimbra
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Turkey
State/province [21] 0 0
Izmir
Country [22] 0 0
Turkey
State/province [22] 0 0
Istanbul
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Manchester
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Stanmore

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Clementia Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03442985
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clementia Call Center (US/Canada Only)
Address 0 0
Country 0 0
Phone 0 0
1-800-750-8710
Fax 0 0
Email 0 0
ClinicalTrials@clementiapharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03442985