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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alternate Intravenous Dosing Arm | Experimental | Subjects will receive drisapersen as a regimen of 3 mg/kg over 1 hr IV weekly throughout the duration of participation. |
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| Primary continuous Dosing Arm | Experimental | Subjects will receive drisapersen 6 mg/kg as SC injection(s) once a week, continuously throughout their duration of participation. |
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| Alternate Intermittent Dosing Arm | Experimental | Subjects will receive drisapersen intermittently, as a regimen of 6 mg/kg as SC injection(s) once a week for 8 weeks followed by 4 weeks of no dosing, throughout their duration of participation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Drisapersen | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to 48 weeks |
| Systolic and diastolic blood pressure measurements to assess the safety and tolerability | Up to 48 weeks | |
| Pulse rate and respiratory rate measurements to assess the safety and tolerability | Up to 48 weeks | |
| Body temperature measurements to assess the safety and tolerability | 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 | 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 | Up to 48 weeks |
| Laboratory tests to assess the safety and tolerability |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
(A) Prior DMD114876 subjects: Subjects who completed both the 24 week double-blind treatment and 24 week post-treatment phases in study DMD114876 OR Subjects who withdrew from the treatment portion of study DMD114876 due to meeting laboratory safety stopping criteria may be eligible to enrol in the extension study if: the laboratory parameters that led to stopping have resolved; the principal investigator (PI) considers the benefit of further treatment with drisapersen outweighs the risk to the individual subject; and following consultation with the Medical Monitor (B) Prior DMD114044 Subjects: US subjects who completed study DMD114044 in another country and who want to return to the US to participate in study DMD115501, upon agreement by a DMD115501 Investigator OR US citizens who participated in DMD114044 but who had to withdraw from the study due to meeting laboratory safety stopping criteria may be eligible to enrol in DMD115501 if: the laboratory parameters that led to stopping have resolved; the PI considers the benefit of further treatment with drisapersen outweighs the risk to the individual subject; and following consultation with the Medical Monitor and upon agreement by a DMD115501 investigator (C) Prior DMD114349 Subjects: US subjects who participated in and completed study DMD114044 in another country and who entered into the ongoing open-label extension study DMD114349 in a country outside the US who wish to withdraw from DMD114349 and return to the US to participate in study DMD115501, upon agreement by a DMD115501 investigator.
Canadian subjects who participated in the DMD114349 study OR Canadian subjects who withdrew from the treatment portion of the study DMD114349 due to meeting laboratory safety stopping criteria may be eligible to enroll in the extension study if the laboratory parameters that led to stopping have resolved; the PI considers the benefit of further treatment with drisapersen outweighs the risk to the individual subject; and following consultation with the Medical Monitor.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| BioMarin Clinical Trials | BioMarin Pharmaceutical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Davis Medical Center | Sacramento | California | 95817 | United States | ||
| Shriner's Hospital for Children Tampa |
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| Drisapersen | Drug | 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 |
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|
| Drisapersen | Drug | 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 |
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Laboratory tests will include hematology, biochemistry and urinalysis parameters
| Up to 48 weeks |
| 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) | 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) | 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) | 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. | Up to 48 weeks |
| Tampa |
| Florida |
| 12502 |
| United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Shriners Hospitals For Children | Portland | Oregon | 97239 | United States |
| Children's & Women's Health Centre of BC | Vancouver | British Columbia | V6H 3V4 | Canada |
| Children's Hospital London Health Sciences Centre | London | Ontario | N6A 4G5 | Canada |
| CHU Ste-Justine | Montreal | Quebec | H3T 1C5 | Canada |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
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| ID | Term |
|---|---|
| C525434 | PRO051 |
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