Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Prosensa Therapeutics
Sponsor:
Information provided by (Responsible Party):
Prosensa Therapeutics
ClinicalTrials.gov Identifier:
NCT01826474
First received: March 20, 2013
Last updated: August 16, 2013
Last verified: February 2013
  Purpose

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 Prosensa Therapeutics:

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 ]

Estimated Enrollment: 45
Study Start Date: January 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (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.

  Eligibility

Ages Eligible for Study:   5 Years to 18 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT01826474

Contacts
Contact: Wai Ling +31 71 3322100 w.mo@prosensa.nl

Locations
Belgium
UZ Leuven Recruiting
Leuven, Belgium
Contact: N Goemans, MD    +32 16 343845    nathalie.goemans@uz.kuleuven.be   
Principal Investigator: N Goemans, MD         
France
Institut de Myologie Recruiting
Paris, France
Contact: T Voit, MD    +33 142 165858    t.voit@institut-myologie.org   
Principal Investigator: T Voit, MD         
Italy
Policlinico Universitario Agostino Gemelli Recruiting
Roma, Italy
Contact: E Mercuri, MD    +39 0630 155 340    eumercuri@gmail.com   
Principal Investigator: E Mercuri, MD         
Netherlands
Leids Universitair Medisch Centrum Not yet recruiting
Leiden, Netherlands
Contact: E Niks, MD    +31 7152 62197    E.H.Niks@lumc.nl   
Principal Investigator: E Niks, MD         
United Kingdom
Great Ormond Street Hospital for Children Not yet recruiting
London, United Kingdom
Contact: F Muntoni, MD    +44 207 405 9200    f.muntoni@ich.ucl.ac.uk   
Principal Investigator: F Muntoni, MD         
Institute of Genetic Medicine International Centre for Life Recruiting
Newcastle, United Kingdom
Contact: V Straub, MD    +44 191 241 8600    volker.straub@newcastle.ac.uk   
Principal Investigator: V Straub, MD         
Sponsors and Collaborators
Prosensa Therapeutics
Investigators
Study Chair: Giles Campion, MD PhD Prosensa Therapeutics
  More Information

Additional Information:
No publications provided

Responsible Party: Prosensa Therapeutics
ClinicalTrials.gov Identifier: NCT01826474     History of Changes
Other Study ID Numbers: PRO045-CLIN-01
Study First Received: March 20, 2013
Last Updated: August 16, 2013
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 Prosensa Therapeutics:
Duchenne muscular dystrophy
DMD
Prosensa
Duchenne

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on October 21, 2014