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Extension Study of Drisapersen in DMD Subjects

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT02636686
First received: December 9, 2015
Last updated: October 27, 2016
Last verified: July 2016
  Purpose
This is a phase IIIb, multi-centre, open-label extension study in male subjects with DMD who previously have been treated with drisapersen, aiming at assessing the safety and efficacy of drisapersen.

Condition Intervention Phase
Duchenne Muscular Dystrophy Drug: Drisapersen Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Drisapersen in Subjects With Duchenne Muscular Dystrophy.

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Weekly through study completion (48 weeks) ]
    Adverse events will be assessed weekly and incidence will be reported

  • Severity of adverse events [ Time Frame: Weekly through study completion (48 weeks) ]
    Adverse event severity will be assessed weekly


Secondary Outcome Measures:
  • Vital signs [ Time Frame: Weekly for 2 weeks, then every 3 months, through study completion (48 weeks) ]
    Vital signs (temperature, blood pressure, pulse and respiratory rate)

  • ECG and echocardiogram [ Time Frame: Screening and week 48 ]
  • Safety hematology and biochemistry parameters, and urinalysis [ Time Frame: Screening and Biweekly, through study completion (48 weeks) ]
    Laboratory panels will be drawn biweekly to assess safety parameters

  • 6MWD [ Time Frame: Baseline, 24 weeks and 48 weeks ]
    Subjects are asked to walk up and down a fixed distance of 25m. Total distance walked within 6 minutes is recorded in meters.

  • North Star Ambulatory Assessment [ Time Frame: Baseline, 24 weeks and 48 weeks ]
    NSAA is a functional scale for use in ambulant DMD children. It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement).

  • Pulmonary function [ Time Frame: Baseline, 24 weeks and 48 weeks ]
    Non-invasive spirometry using a spirometer will be conducted to assess forced vital capacity, forced expiratory volume. In addition, selected sites may perform Maximum Inspiratory and Expiratory Pressure (MIP and MEP).

  • Performance of Upper Limb [ Time Frame: Baseline, 24 weeks and 48 weeks ]
    Upper limb muscle function in the shoulder, elbow, wrist and hand dimensions will be assessed using a set of standardized equipment.

  • Patient questionnaire: DMD Functioning and activities survey (PODCI) [ Time Frame: Baseline, 24 weeks and 48 weeks ]
  • Patient questionnaire: EuroQol EG-5D-5L Health Utility Score [ Time Frame: Baseline, 24 weeks and 48 weeks ]
  • Dixon and T2 assessed by MRI [ Time Frame: Screening, 24 weeks and 48 weeks ]
    At selected sites only.


Enrollment: 24
Study Start Date: December 2015
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open label - continuous SC
Continuous SC injections. Subjects will receive drisapersen via SC injections at a dose of 6 mg/kg weekly
Drug: Drisapersen
Subjects will receive 6 mg/kg of drisapersen by subcutaneous injection once weekly. If subjects have experienced an intolerable injection site reaction(s), in consultation with the investigator, the subject may be allowed intermittent injections (8 weeks on/4 weeks off) or weekly intravenous infusions of 3 or 6 mg/kg
Other Name: PRO051
Experimental: Open label - intermittent SC
Intermittent SC injections. Subjects will receive drisapersen via SC injections at a dose of 6 mg/kg weekly for 8 weeks, followed by 4 weeks off treatment, and will then repeat these cycles.
Drug: Drisapersen
Subjects will receive 6 mg/kg of drisapersen by subcutaneous injection once weekly. If subjects have experienced an intolerable injection site reaction(s), in consultation with the investigator, the subject may be allowed intermittent injections (8 weeks on/4 weeks off) or weekly intravenous infusions of 3 or 6 mg/kg
Other Name: PRO051
Experimental: Open label - continuous IV
Continuous IV injections. Subjects will receive drisapersen via IV infusions at a dose of 3 or 6 mg/kg weekly
Drug: Drisapersen
Subjects will receive 6 mg/kg of drisapersen by subcutaneous injection once weekly. If subjects have experienced an intolerable injection site reaction(s), in consultation with the investigator, the subject may be allowed intermittent injections (8 weeks on/4 weeks off) or weekly intravenous infusions of 3 or 6 mg/kg
Other Name: PRO051

Detailed Description:

This is a phase IIIb, multi-centre, open-label extension study in male subjects with DMD who have previously been treated with drisapersen.

This study aims to enroll up to approximately 220 subjects. The primary dosing arm is drisapersen 6 mg/kg as subcutaneous (SC) injection(s) once a week. All subjects starting with subcutaneous injections will receive a loading dose of twice weekly 6mg/kg drisapersen for the first three weeks of treatment. This study does not have a minimum duration of participation. Subjects will have varying times of study participation depending on when they enter from one of the eligible studies and will be permitted to continue the study until such a time that they withdraw based on protocol-defined criteria, or BioMarin stops the study. Subjects naïve to treatment are not eligible for participation in this study

For subjects who have previously experienced significant safety or tolerability issues in one of the eligible studies, or who experience these during this study, there is the potential of an alternate intermittent dosing arm. This will be agreed in advance with the Medical Monitor.

For subjects who have previously experienced significant injection site reactions in an earlier drisapersen study, or who experience similar reaction(s) during this study, there is the potential to be dosed intravenously.

  Eligibility

Ages Eligible for Study:   5 Years to 80 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Any subject who has been previously treated with an exon 51 skipping antisense oligonucleotide (drisapersen or eteplirsen) and is not eligible for another ongoing drisapersen study. Subjects who withdrew from the previous studies due to meeting laboratory safety stopping criteria may be eligible to enroll if:
  2. The laboratory parameters that led to stopping have resolved; benefit of further treatment with drisapersen outweighs the risk to the individual subject; and following consultation with the Medical Monitor.
  3. Subjects with DMD mutation/deletion within the dystrophin gene and correctable by drisapersen-induced DMD exon 51 skipping.
  4. Male subjects age >5 at screening in whom the investigator considers treatment with drisapersen is likely to lead to improvement or prevent worsening of the condition.
  5. Continued use of glucocorticoids for a minimum of 60 days prior to study entry with a reasonable expectation that the subject will remain on glucocorticoids for the duration of this study. Changes to or cessation of glucocorticoids will be at the discretion of the investigator conducting this study in consultation with the subject/parent and Medical Monitor.
  6. Willing and able to comply with all study requirements and procedures (with the exception of those assessments requiring a subject to be ambulant, for those subjects who have lost ambulation).
  7. Able to give informed assent and/or consent in writing by the subject and/or parent(s)/legal guardian (according to local regulations)

Exclusion Criteria:

  1. Subjects who have previously been treated with drisapersen and who had a serious adverse experience or who met safety stopping criteria that remains unresolved, which in the opinion of the investigator could have been attributable to drisapersen. Once resolved, subject may be eligible to enter the study following investigator consultation with the Medical Monitor.
  2. Use of anticoagulants, anti-thrombotics or antiplatelet agents within 28 days of the first re-dosing of drisapersen. Chronic use of anticoagulants, anti-thrombotics or antiplatelet agents is prohibited during the study. As needed dosing (pro re nata - PRN) may be acceptable (except for aspirin) following discussion with the Medical Monitor.
  3. Participation in any investigational clinical trial within 3 months prior to start or during this study (except for other drisapersen studies). If subjects have participated in any other study within the last 6 months this should be discussed with the Medical Monitor prior to start of this study.
  4. History of significant medical disorder which may confound the interpretation of safety data (e.g. current or history of renal or liver disease/impairment, history of inflammatory illness)
  5. Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction <45% at start of this study, the investigator should discuss inclusion of subject in this study with the Medical Monitor.
  6. A platelet count under the lower limit of normal (LLN) at start of this study. A re-test is possible at a later stage, and if within normal range, the subject may enter 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: NCT02636686

  Show 39 Study Locations
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Derry Ridgway, MD BioMarin Pharmaceutical
  More Information

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT02636686     History of Changes
Other Study ID Numbers: BMN-051-302
Study First Received: December 9, 2015
Last Updated: October 27, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by BioMarin Pharmaceutical:
DMD
Duchenne Muscular Dystrophy
Drisapersen
Kyndrisa
exon-skipping
exon-51
BMN-051-302
051-302

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

ClinicalTrials.gov processed this record on August 18, 2017