- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01826474
Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy
December 6, 2017 updated by: BioMarin Pharmaceutical
A Phase IIb, Open-label Study to Assess the Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of Multiple Subcutaneous Doses of PRO045 in Subjects With Duchenne Muscular Dystrophy
The purpose of the study is to see whether PRO045 is safe and effective to use as medication for Duchenne Muscular Dystrophy (DMD) patients with a mutation around location 45 in the DNA for the dystrophin protein.
Study Overview
Status
Terminated
Conditions
Detailed Description
A phase IIb, open-label, multiple-dose study.
The study consists of two phases; a dose escalation phase (with subsequent dose-titration) and a 48-week treatment phase.
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 2
- Phase 1
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
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Leuven, Belgium
- UZ Leuven
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Paris, France
- Institut de Myologie
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Roma, Italy
- Policlinico Universitario Agostino Gemelli
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Leiden, Netherlands
- Leids Universitair Medisch Centrum
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London, United Kingdom
- Great Ormond Street Hospital for Children
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Newcastle, United Kingdom
- Institute of Genetic Medicine International Centre for Life
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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
Ages Eligible for Study
5 years to 18 years (ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO045 confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition Amplification/Internal Primer) or HRMCA (High-Resolution Melting Curve Analysis), and correctable by PRO045-induced DMD exon 45 skipping in cultured skin-derived myo-converted fibroblasts.
- Ambulant boys aged at least 5 years on the day of first dosing able to walk for at least 230 meters in the 6 minute walking distance (6MWD) test at first screening visit and also at the baseline visit. In addition, 2 of the 3 pre-treatment 6MWD tests (screen 1, screen 2, baseline) must be within +/-30 metres of each other prior to first PRO045 administration.
- Adequate quality for biopsy (confirmed with MRI) of the lateral head of the gastrocnemius muscle. An alternative muscle may be considered for biopsy but only following discussion between the Principal Investigator and the Prosensa Medical Monitor.
- Life expectancy of at least 3 years after inclusion in the study.
- Glucocorticosteroid use which is stable for at least 3 months prior to first PRO045 administration. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first PRO045 administration.
- Willing and able to adhere to the study visit schedule and other protocol requirements.
- Written informed consent signed (by parent(s)/legal guardian and/or the subject, according to the local regulations).
- In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
Exclusion Criteria:
- Known presence of dystrophin in ≥5% of fibres in a pre-study diagnostic muscle biopsy (i.e. historic muscle biopsy taken prior to written informed consent for this study).
- Current or history of liver disease or impairment.
- Current or history of renal disease or impairment.
- At least two aPTT above ULN within the last month.
- Screening platelet count below the lower limit of normal (LLN).
- Acute illness within 4 weeks prior to first dose of PRO045 which may interfere with the study assessments.
- Severe mental retardation or behavioural problems which in the opinion of the investigator prohibits participation in this study.
- Severe cardiomyopathy which in the opinion of the investigator prohibits participation in this study. If a subject has a left ventricular ejection fraction <45% at screening, the investigator should discuss inclusion of the subject with the Medical Monitor.
- Expected need for daytime mechanical ventilation within the next year.
- Use of anticoagulants, antithrombotics or antiplatelet agents.
- Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of the screening for the study.
- Use of nutritional or herbal supplements which, in the opinion of the investigator, may influence muscle performance, within 1 month of the study.
- Use of any other investigational product or participation in another trial with an investigational product, within 6 months prior to the start of the screening for the study.
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: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: PRO045, cohort 1
0.15 mg/kg until dose-titration
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Subcutaneous injection
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Experimental: PRO045, cohort 2
1.0 mg/kg until dose-titration
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Subcutaneous injection
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Experimental: PRO045, cohort 3
3.0 mg/kg until dose-titration
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Subcutaneous injection
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Experimental: PRO045, cohort 4
6.0 mg/kg until dose-titration
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Subcutaneous injection
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Experimental: PRO045, cohort 5
9.0 mg/kg until move to 48 week treatment phase
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Subcutaneous injection
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Experimental: PRO045, cohort 6
48 week treatment phase
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Subcutaneous injection
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Change from baseline in 6 minute walk test
Time Frame: after 48 weeks of treatment phase
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after 48 weeks of treatment phase
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Muscle function
Time Frame: after 48 weeks of treatment phase
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after 48 weeks of treatment phase
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Muscle strength
Time Frame: after 48 weeks treatment phase
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after 48 weeks treatment phase
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Performance of upper limb
Time Frame: after 48 weeks of treatment phase
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after 48 weeks of treatment phase
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Functional outcomes questionnaire
Time Frame: after 48 weeks of treatment
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after 48 weeks of treatment
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Safety
Time Frame: after 48 weeks of treatment phase
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after 48 weeks of treatment phase
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: T. Voit, MD PhD, Institut de Myologie
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.
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)
January 1, 2013
Primary Completion (Actual)
August 31, 2016
Study Completion (Actual)
August 31, 2016
Study Registration Dates
First Submitted
March 20, 2013
First Submitted That Met QC Criteria
April 3, 2013
First Posted (Estimate)
April 8, 2013
Study Record Updates
Last Update Posted (Actual)
December 8, 2017
Last Update Submitted That Met QC Criteria
December 6, 2017
Last Verified
December 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO045-CLIN-01
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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