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Trial record 47 of 1002 for:    BMD

Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy

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: NCT01826474
Recruitment Status : Terminated
First Posted : April 8, 2013
Last Update Posted : December 8, 2017
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE March 20, 2013
First Posted Date  ICMJE April 8, 2013
Last Update Posted Date December 8, 2017
Actual Study Start Date  ICMJE January 2013
Actual Primary Completion Date August 31, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2013)
Change from baseline in 6 minute walk test [ Time Frame: after 48 weeks of treatment phase ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01826474 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2013)
  • Muscle function [ Time Frame: after 48 weeks of treatment phase ]
  • Muscle strength [ Time Frame: after 48 weeks treatment phase ]
  • Performance of upper limb [ Time Frame: after 48 weeks of treatment phase ]
  • Functional outcomes questionnaire [ Time Frame: after 48 weeks of treatment ]
  • Safety [ Time Frame: after 48 weeks of treatment phase ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE
  • Drug: PRO045, 0.15 mg/kg/week
    Subcutaneous injection
  • Drug: PRO045, 1.0 mg/kg/week
    Subcutaneous injection
  • Drug: PRO045, 3.0 mg/kg/week
    Subcutaneous injection
  • Drug: PRO045, 6.0 mg/kg/week
    Subcutaneous injection
  • Drug: PRO045, 9.0 mg/kg/week
    Subcutaneous injection
  • Drug: PRO045, selected dose
    Subcutaneous injection
Study Arms  ICMJE
  • Experimental: PRO045, cohort 1
    0.15 mg/kg until dose-titration
    Intervention: Drug: PRO045, 0.15 mg/kg/week
  • Experimental: PRO045, cohort 2
    1.0 mg/kg until dose-titration
    Intervention: Drug: PRO045, 1.0 mg/kg/week
  • Experimental: PRO045, cohort 3
    3.0 mg/kg until dose-titration
    Intervention: Drug: PRO045, 3.0 mg/kg/week
  • Experimental: PRO045, cohort 4
    6.0 mg/kg until dose-titration
    Intervention: Drug: PRO045, 6.0 mg/kg/week
  • Experimental: PRO045, cohort 5
    9.0 mg/kg until move to 48 week treatment phase
    Intervention: Drug: PRO045, 9.0 mg/kg/week
  • Experimental: PRO045, cohort 6
    48 week treatment phase
    Intervention: Drug: PRO045, selected dose
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: October 27, 2016)
15
Original Estimated Enrollment  ICMJE
 (submitted: April 3, 2013)
45
Actual Study Completion Date  ICMJE August 31, 2016
Actual Primary Completion Date August 31, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 5 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Netherlands,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01826474
Other Study ID Numbers  ICMJE PRO045-CLIN-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BioMarin Pharmaceutical
Study Sponsor  ICMJE BioMarin Pharmaceutical
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: T. Voit, MD PhD Institut de Myologie
PRS Account BioMarin Pharmaceutical
Verification Date December 2017

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