This is a phase III, multicenter, open-label, uncontrolled extension study in male subjects with DMD open to eligible US and Canadian subjects who previously participated in the following studies of drisapersen: DMD114876, DMD114044 and DMD114349. Subjects will receive 6mg/kg subcutaneous drisapersen on a weekly basis. For subjects who have previously experienced significant safety or tolerability issues or who experience these during the study, there is the potential of an alternate intermittent dosing arm that will be given as a regimen of 6 mg/kg weekly for 8 weeks followed by 4 weeks off treatment. For subjects who experience or have previously experienced significant safety/tolerability issues, side effects or reactions or intermittent dosing, intravenous dosing will be made available.
In Part A of the study (DMD115501, original protocol), 21 subjects entered the study at 3 US sites and completed up to 14 weeks of treatment, and up to 22 weeks of follow-up. This protocol amendment, Part B of the study will include up to 13 more US and Canadian centers, and up to 51 more subjects. In total the study will enroll approximately 72 subjects. All subjects will commence Part B at screening and follow the study schedule. The primary dosing arm is drisapersen 6 mg/kg as SC injection(s) once a week. For subjects who have previously experienced significant safety or tolerability issues or who experience these during the study, there is the potential of an alternate intermittent dosing arm that will be given as a regimen of 6 mg/kg/wk for 8 weeks followed by 4 weeks of treatment. For subjects who experience or have previously experienced significant safety/tolerability issues, intravenous dosing will be made available. 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 in this study until such a time that they withdraw based on protocol-defined criteria, or BioMarin stops the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Drisapersen will be supplied as 3 mL (milliliter) vials containing 1 mL sterile solution of 200 mg/mL strength. Each subject will receive drisapersen 3 mg/kg administered IV once a week, continuously throughout their duration of participation
Drisapersen will be supplied as 3 mL (milliliter) vials containing 1 mL sterile solution of 220 mg/mL strength. Each subject will receive drisapersen 6 mg/kg administered SC once a week, either continuously or intermittently (for 8 weeks, followed by 4 weeks of no dosing) throughout their duration of participation
Drisapersen will be supplied as 3 mL (milliliter) vials containing 1 mL sterile solution of 220 mg/mL strength. Each subject will receive drisapersen 6 mg/kg administered SC once a week, either continuously or intermittently (for 8 weeks, followed by 4 weeks of no dosing) throughout their duration of participation
UC Davis Medical Center
Sacramento, California, United States
Shriner's Hospital for Children Tampa
Tampa, Florida, United States
University of Iowa
Iowa City, Iowa, United States
Kennedy Krieger Institute
Baltimore, Maryland, United States
University of Minnesota
Minneapolis, Minnesota, United States
Columbia University Medical Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Shriners Hospitals For Children
Portland, Oregon, United States
...and 3 more locations
Incidence and severity of Adverse Events (AEs)
AEs will be assessed from Pre-baseline visit until 20 weeks after the subject has either completed the study or withdrawn from treatment early. AEs are any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time frame: Up to 48 weeks
Systolic and diastolic blood pressure measurements to assess the safety and tolerability
Time frame: Up to 48 weeks
Pulse rate and respiratory rate measurements to assess the safety and tolerability
Time frame: Up to 48 weeks
Body temperature measurements to assess the safety and tolerability
Time frame: Up to 48 weeks
12-Lead Electrocardiogram (ECG) measurements to assess the safety and tolerability
The following parameters will be assessed: heart rate, intervals, corrected QT (QTc) interval (Bazett). In addition, an assessment of abnormal morphology will be made
Time frame: Up to 48 weeks
Echocardiogram measurements to assess the safety and tolerability
The following parameters will be assessed: Left ventricular end-diastolic/end-systolic wall thickness (septum, posterior wall), fractional shortening (SF) and ejection fraction (LVEF) will be derived from M-mode (from the parasternal long-axis or short-axis view) for quantitative measurements
Time frame: Up to 48 weeks
Laboratory tests to assess the safety and tolerability
Laboratory tests will include hematology, biochemistry and urinalysis parameters
Time frame: Up to 48 weeks
Muscle function assessment using 6-minute walking distance (6MWD) test
Subjects will be asked to walk, at their own preferred speed, up and down a fixed distance until they are told to stop after 6 minutes. The subjects are warned of the time and are told that they may stop earlier if they feel unable to continue. The total distance walked within 6 minutes (or until the subject stopped in case of early termination of the test) will be recorded in meters, as well as any falls. Subjects who became non-ambulant in the prior study or who become non-ambulant during this study will not be able to perform this
Time frame: Up to 48 weeks
North Star Ambulatory Assessment (NSAA)
The NSAA is a functional scale devised from the Hammersmith Scale of Motor Ability specifically for use in ambulant children with DMD. It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). The scale assesses activities that are required for ambulatory activity and includes items that are rarely achieved in untreated DMD (jump, hop, raise head) as well as items that are known to progressively deteriorate over time (stand from a chair, walk)
Time frame: Up to 48 weeks
Pulmonary function assessment
Non-invasive spirometry will be conducted to determine actual and percent values for Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV1)
Time frame: Up to 48 weeks
Time to major disease milestones
Major disease milestones are defined as those events that occurred since the last time they were assessed and include the following muscular dystrophy-related milestones: Achilles tendon contracture, hamstring contracture, lumbar lordosis, limb skeletal deformity, loss of ambulation, respiratory support during the day, respiratory support during sleep, scoliosis, use of leg braces, use of orthoses, use of special shoes, using Gower's maneuver or other milestone (to be specified)
Time frame: Up to 48 weeks
Functional Outcomes assessment
One assessments will be completed to observe the changes in the ability of the subject to perform usual day-to-day activities during the study: Functional Outcomes Survey - by the family/caregivers who attends the scheduled clinic visit.
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Time frame: Up to 48 weeks