A Study of the Safety, Tolerability & Efficacy of Long-term Administration of Drisapersen in US & Canadian Subjects

NCT01803412 | Terminated Phase 3 FDA Drug

• 1 other identifier: DMD115501
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 13

Brief Summary

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.

Conditions

Muscular Dystrophies

Keywords

GSK2402968; open-label extension; safety; drisapersen; Duchenne Muscular Dystrophy; tolerability; Quality of Life

Outcome Measures

Primary Outcomes (7)

• 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  AEs will be assessed from Pre-baseline visit until 20 weeks after the subject has either completed the study or withdrawn from treatment early.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

  Laboratory tests will include hematology, biochemistry and urinalysis parameters

  Up to 48 weeks

Secondary Outcomes (5)

• Muscle function assessment using 6-minute walking distance (6MWD) test

  Up to 48 weeks

• North Star Ambulatory Assessment (NSAA)

  Up to 48 weeks

• Pulmonary function assessment

  Up to 48 weeks

• Time to major disease milestones

  Up to 48 weeks

• Functional Outcomes assessment

  Up to 48 weeks

Study Arms (3)

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.

Drug: Drisapersen

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.

Drug: Drisapersen

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.

Drug: Drisapersen

Interventions

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

Also known as: BMN 051

Alternate Intravenous Dosing Arm

Eligibility Criteria

• Age: 5 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participation in an eligible drisapersen study as follows:
• (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.
• Continued use of glucocorticoids for a minimum of 60 days prior to study entry with a reasonable expectation that the subject will remain on steroids for the duration of the study. Changes to or cessation of glucocorticoids will be at the discretion of the PI in consultation with the subject/parent and the Medical Monitor. If subject is not on steroids, involvement in the study needs to be discussed with the medical monitor.
• Willing and able to comply with all protocol requirements and procedures (with the exception of those assessments requiring a subject to be ambulant, for those subjects who have lost ambulation)
• Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations)

You may not qualify if:

• Subject had a serious adverse experience or who met safety stopping criteria that remains unresolved from studies DMD114876, DMD114044, or DMD114349, which in the opinion of the investigator could have been attributable to study medication, and which is ongoing. Once resolved, subject may be eligible to enrol following PI consultation with the Medical Monitor
• Use of anticoagulants, antithrombotics or antiplatelet agents, or previous treatment with investigational drugs except for drisapersen, within 28 days of the first administration of study medication
• Participation in any other investigational clinical trial within 30 days prior to the start of screening, or during this clinical study. If subject has participated in any other study within 6 months, this should be discussed with the medical monitor prior to study entry.
• History of significant medical disorder which may confound the interpretation of either efficacy or safety data (e.g. current or history of renal or liver disease/impairment, history of inflammatory illness)
• A platelet count under the lower limit of normal at screening. A re-test within the screening period is permissible and if within normal range the subject may enter the study.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (13)

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Shriner's Hospital for Children Tampa

Tampa, Florida, 12502, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Shriners Hospitals For Children

Portland, Oregon, 97239, United States

Location

Children's & Women's Health Centre of BC

Vancouver, British Columbia, V6H 3V4, Canada

Location

Children's Hospital London Health Sciences Centre

London, Ontario, N6A 4G5, Canada

Location

CHU Ste-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

MeSH Terms

Conditions

Muscular Dystrophies; Muscular Dystrophy, Duchenne

Interventions

PRO051

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• BioMarin Clinical Trials

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2013
• First Posted: March 4, 2013
• Study Start: May 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: October 1, 2016
• Last Updated: June 14, 2018

Record last verified: 2018-06

Locations

CA (3); US (10)