Overview

This trial has been terminated.

Condition duchenne muscular dystrophy
Treatment drisapersen
Phase phase 3
Sponsor BioMarin Pharmaceutical
Start date December 2015
End date October 2016
Trial size 24 participants
Trial identifier NCT02636686, BMN-051-302

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Continuous SC injections. Subjects will receive drisapersen via SC injections at a dose of 6 mg/kg weekly
drisapersen PRO051
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
(Experimental)
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.
drisapersen PRO051
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
(Experimental)
Continuous IV injections. Subjects will receive drisapersen via IV infusions at a dose of 3 or 6 mg/kg weekly
drisapersen PRO051
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

Primary Outcomes

Measure
Incidence of adverse events
time frame: Weekly through study completion (48 weeks)
Severity of adverse events
time frame: Weekly through study completion (48 weeks)

Secondary Outcomes

Measure
Vital signs
time frame: Weekly for 2 weeks, then every 3 months, through study completion (48 weeks)
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)
6MWD
time frame: Baseline, 24 weeks and 48 weeks
North Star Ambulatory Assessment
time frame: Baseline, 24 weeks and 48 weeks
Pulmonary function
time frame: Baseline, 24 weeks and 48 weeks
Performance of Upper Limb
time frame: Baseline, 24 weeks and 48 weeks
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

Eligibility Criteria

Male participants from 5 years up to 80 years old.

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.

Additional Information

Official title An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Drisapersen in Subjects With Duchenne Muscular Dystrophy.
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by BioMarin Pharmaceutical.