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Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy

This study has been terminated.
Information provided by (Responsible Party):
BioMarin Pharmaceutical Identifier:
First received: March 20, 2013
Last updated: October 27, 2016
Last verified: June 2015
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.

Condition Intervention Phase
Duchenne Muscular Dystrophy
Drug: PRO045, 0.15 mg/kg/week
Drug: PRO045, 1.0 mg/kg/week
Drug: PRO045, 3.0 mg/kg/week
Drug: PRO045, 6.0 mg/kg/week
Drug: PRO045, 9.0 mg/kg/week
Drug: PRO045, selected dose
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Change from baseline in 6 minute walk test [ Time Frame: after 48 weeks of treatment phase ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Muscle function [ Time Frame: after 48 weeks of treatment phase ] [ Designated as safety issue: No ]
  • Muscle strength [ Time Frame: after 48 weeks treatment phase ] [ Designated as safety issue: No ]
  • Performance of upper limb [ Time Frame: after 48 weeks of treatment phase ] [ Designated as safety issue: No ]
  • Functional outcomes questionnaire [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: after 48 weeks of treatment phase ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: January 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PRO045, cohort 1
0.15 mg/kg until dose-titration
Drug: PRO045, 0.15 mg/kg/week
Subcutaneous injection
Experimental: PRO045, cohort 2
1.0 mg/kg until dose-titration
Drug: PRO045, 1.0 mg/kg/week
Subcutaneous injection
Experimental: PRO045, cohort 3
3.0 mg/kg until dose-titration
Drug: PRO045, 3.0 mg/kg/week
Subcutaneous injection
Experimental: PRO045, cohort 4
6.0 mg/kg until dose-titration
Drug: PRO045, 6.0 mg/kg/week
Subcutaneous injection
Experimental: PRO045, cohort 5
9.0 mg/kg until move to 48 week treatment phase
Drug: PRO045, 9.0 mg/kg/week
Subcutaneous injection
Experimental: PRO045, cohort 6
48 week treatment phase
Drug: PRO045, selected dose
Subcutaneous injection

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.

Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Life expectancy of at least 3 years after inclusion in the study.
  5. 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.
  6. Willing and able to adhere to the study visit schedule and other protocol requirements.
  7. Written informed consent signed (by parent(s)/legal guardian and/or the subject, according to the local regulations).
  8. 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:

  1. 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).
  2. Current or history of liver disease or impairment.
  3. Current or history of renal disease or impairment.
  4. At least two aPTT above ULN within the last month.
  5. Screening platelet count below the lower limit of normal (LLN).
  6. Acute illness within 4 weeks prior to first dose of PRO045 which may interfere with the study assessments.
  7. Severe mental retardation or behavioural problems which in the opinion of the investigator prohibits participation in this study.
  8. 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.
  9. Expected need for daytime mechanical ventilation within the next year.
  10. Use of anticoagulants, antithrombotics or antiplatelet agents.
  11. Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of the screening for the study.
  12. Use of nutritional or herbal supplements which, in the opinion of the investigator, may influence muscle performance, within 1 month of the study.
  13. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01826474

UZ Leuven
Leuven, Belgium
Institut de Myologie
Paris, France
Policlinico Universitario Agostino Gemelli
Roma, Italy
Leids Universitair Medisch Centrum
Leiden, Netherlands
United Kingdom
Great Ormond Street Hospital for Children
London, United Kingdom
Institute of Genetic Medicine International Centre for Life
Newcastle, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Principal Investigator: T. Voit, MD PhD Institut de Myologie
  More Information

Additional Information:
Responsible Party: BioMarin Pharmaceutical Identifier: NCT01826474     History of Changes
Other Study ID Numbers: PRO045-CLIN-01 
Study First Received: March 20, 2013
Last Updated: October 27, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Italy: National Institute of Health

Keywords provided by BioMarin Pharmaceutical:
Duchenne muscular dystrophy

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked processed this record on January 14, 2017