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A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration

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ClinicalTrials.gov Identifier: NCT01910649
Recruitment Status : Terminated (Regulatory approval was not obtained for drisapersen, hence BioMarin is stopping the development of all exon skipping oligonucleotides in DMD.)
First Posted : July 29, 2013
Last Update Posted : November 7, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of the extension phase of this study is to determine whether Drisapersen is effective in the treatment of boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.

Condition or disease Intervention/treatment Phase
Muscular Dystrophies Drug: Drisapersen Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for Intravenous Dosing as an Alternative Route of Administration
Study Start Date : March 2008
Primary Completion Date : September 2016
Study Completion Date : September 2016


Arms and Interventions

Arm Intervention/treatment
Experimental: Drisapersen
Extension phase of treatment. Intravenous dosing of drisapersen will be investigated as an alternative route of administration
Drug: Drisapersen
Subcutaneous and Intravenous
Other Name: PRO051


Outcome Measures

Primary Outcome Measures :
  1. Acute phase: Safety data [ Time Frame: 18 weeks ]
    Summarized per dose group

  2. Acute phase and Continued Treatment Phase : Pharmacokinetics measured by T1/2, Cmax, Ctrough, 7d, tmax, and volume of distribution and clearance [ Time Frame: 18 weeks ]
    Plasma concentration versus time profiles of PRO051 (GSK2402968)

  3. Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs) [ Time Frame: 72 weeks ]
    Change from baseline and summarized values

  4. Continued Treatment Phase :Safety as assessed by laboratory parameters [ Time Frame: 72 weeks ]
    Change from baseline and summarized values


Secondary Outcome Measures :
  1. Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA) [ Time Frame: 18 weeks ]
  2. Acute phase: Presence of dystrophin expression [ Time Frame: 18 weeks ]
  3. Acute phase: Muscle function [ Time Frame: 18 weeks ]
    Timed tests and 6-minutes walk

  4. Acute phase: Muscle strength [ Time Frame: 18 weeks ]
    Quantitative Muscle Testing [QMT]- Cooperative International Neuromuscular Research Group (CINRG) and Manual Muscle Testing [MMT]

  5. Continued Treatment Phase: Exon skip efficiency [ Time Frame: 72 weeks ]
  6. Continued Treatment Phase Dystrophin expression in muscle biopsy [ Time Frame: 72 weeks ]
  7. Continued Treatment Phase: Muscle function [ Time Frame: 300 weeks ]
    Timed tests and 6-minutes walk

  8. Continued Treatment Phase: Muscle strength [ Time Frame: 300 weeks ]
    Handheld myometry and spirometry


Eligibility Criteria

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Ages Eligible for Study:   5 Years to 16 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Boys aged between 5 and 16 years inclusive.
  • Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO051.
  • Not ventilator dependent.
  • Life expectancy of at least six months.
  • No previous treatment with investigational medicinal treatment within six months prior to the study.
  • Willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  • Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during screening.
  • Known presence of dystrophin in 5% of fibers in a pre-study diagnostic muscle biopsy.
  • Severe muscle abnormalities defined as increased signal intensity in >50% of the tibialis anterior muscle at MRI.
  • FEV1 and/or FVC <60% of predicted.
  • Current or history of liver or renal disease.
  • Acute illness within 4 weeks prior to treatment (Day 1) which may interfere with the measurements.
  • Severe mental retardation which in the opinion of the investigator prohibits participation in this study.
  • Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study.
  • Need for mechanical ventilation.
  • Creatinine concentration above 1.5 times the upper limit of normal (age corrected).
  • Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment.
  • Use of anticoagulants, antithrombotics or antiplatelet agents.
  • Subject has donated blood less than 90 days before the start of the study.
  • Current or history of drug and/or alcohol abuse.
  • Participation in another trial with an investigational product.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01910649


Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Principal Investigator: N Goemans, Dr. UZ Leuven
More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01910649     History of Changes
Other Study ID Numbers: 114673
2007-004819-54 ( EudraCT Number )
First Posted: July 29, 2013    Key Record Dates
Last Update Posted: November 7, 2016
Last Verified: November 2016

Keywords provided by BioMarin Pharmaceutical:
drisapersen

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