Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy

NCT01826474 | Terminated Phase 1 DMC

• 1 other identifier: PRO045-CLIN-01
• Study Type: interventional
• Target: 15
• Locations: 5 countries
• Sites: 6

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.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; DMD; Prosensa; Duchenne

Outcome Measures

Primary Outcomes (1)

• Change from baseline in 6 minute walk test

  after 48 weeks of treatment phase

Secondary Outcomes (5)

• Muscle function

  after 48 weeks of treatment phase

• Muscle strength

  after 48 weeks treatment phase

• Performance of upper limb

  after 48 weeks of treatment phase

• Functional outcomes questionnaire

  after 48 weeks of treatment

• Safety

  after 48 weeks of treatment phase

Study Arms (6)

PRO045, cohort 1

EXPERIMENTAL

0.15 mg/kg until dose-titration

Drug: PRO045, 0.15 mg/kg/week

PRO045, cohort 2

EXPERIMENTAL

1.0 mg/kg until dose-titration

Drug: PRO045, 1.0 mg/kg/week

PRO045, cohort 3

EXPERIMENTAL

3.0 mg/kg until dose-titration

Drug: PRO045, 3.0 mg/kg/week

PRO045, cohort 4

EXPERIMENTAL

6.0 mg/kg until dose-titration

Drug: PRO045, 6.0 mg/kg/week

PRO045, cohort 5

EXPERIMENTAL

9.0 mg/kg until move to 48 week treatment phase

Drug: PRO045, 9.0 mg/kg/week

PRO045, cohort 6

EXPERIMENTAL

48 week treatment phase

Drug: PRO045, selected dose

Interventions

PRO045, 0.15 mg/kg/week DRUG

Subcutaneous injection

PRO045, cohort 1

PRO045, 1.0 mg/kg/week DRUG

Subcutaneous injection

PRO045, cohort 2

PRO045, 3.0 mg/kg/week DRUG

Subcutaneous injection

PRO045, cohort 3

PRO045, 6.0 mg/kg/week DRUG

Subcutaneous injection

PRO045, cohort 4

PRO045, 9.0 mg/kg/week DRUG

Subcutaneous injection

PRO045, cohort 5

PRO045, selected dose DRUG

Subcutaneous injection

PRO045, cohort 6

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (6)

UZ Leuven

Leuven, Belgium

Location

Institut de Myologie

Paris, France

Location

Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Leids Universitair Medisch Centrum

Leiden, Netherlands

Location

Great Ormond Street Hospital for Children

London, United Kingdom

Location

Institute of Genetic Medicine International Centre for Life

Newcastle, United Kingdom

Location

Related Links

• BioMarin website

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• T. Voit, MD PhD

  Institut de Myologie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2013
• First Posted: April 8, 2013
• Study Start: January 1, 2013
• Primary Completion: August 31, 2016
• Study Completion: August 31, 2016
• Last Updated: December 8, 2017

Record last verified: 2017-12

Locations

GB (2); NL (1); IT (1); BE (1); FR (1)