A Study of the Safety, Tolerability and Efficacy of Long-term Administration of Drisapersen in United States (US) Subjects With Duchenne Muscular Dystrophy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Prosensa Therapeutics
ClinicalTrials.gov Identifier:
NCT01803412
First received: February 28, 2013
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

This is a phase III, multicenter, open-label, uncontrolled extension study. The Purpose of this study is to evaluate the effects of long-term administration of drisapersen in US male subjects with Duchenne Muscular Dystrophy (DMD), who have previously participated in one of the following eligible studies of drisapersen: DMD114876, DMD114044 and DMD114349. This study does not have a minimum duration of participation. The study participation time of the subjects will vary 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 GlaxoSmithKline (GSK) stops the study. Subjects will receive drisapersen 6 milligrams (mg)/kilogram (kg) as Subcutaneous (SC) injection(s) once a week (wk), continuously throughout their duration of participation. For subjects who cannot continue on 6 mg/kg/wk for safety and/or tolerability reasons, but who may benefit from drisapersen, an alternate intermittent dosing will be given as a regimen of 6 mg/kg/wk for 8 weeks followed by 4 weeks off treatment. Subjects withdrawing from this study but who do not withdraw consent, will be followed up for safety and progress as clinically indicated, for at least 20 weeks after the last dose of study treatment, after which a follow-up telephone call will be conducted. If subjects withdraw, they will not be replaced.


Condition Intervention Phase
Muscular Dystrophies
Drug: Drisapersen
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Drisapersen (GSK2402968) in US Subjects With Duchenne Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by Prosensa Therapeutics:

Primary Outcome Measures:
  • Incidence and severity of Adverse Events (AEs) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    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

  • Systolic and diastolic blood pressure measurements to assess the safety and tolerability [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
  • Pulse rate and respiratory rate measurements to assess the safety and tolerability [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
  • Body temperature measurements to assess the safety and tolerability [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
  • 12-Lead Electrocardiogram (ECG) measurements to assess the safety and tolerability [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    The following parameters will be assessed: heart rate, intervals, corrected QT (QTc) interval (Bazett). In addition, an assessment of abnormal morphology will be made

  • Echocardiogram measurements to assess the safety and tolerability [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    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

  • Laboratory tests to assess the safety and tolerability [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    Laboratory tests will include hematology, biochemistry and urinalysis parameters


Secondary Outcome Measures:
  • Muscle function assessment using 6-minute walking distance (6MWD) test [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    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

  • North Star Ambulatory Assessment (NSAA) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    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)

  • Pulmonary function assessment [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    Non-invasive spirometry will be conducted to determine actual and percent values for Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV1)

  • Frequency of accidental falls during 6MWD [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    The number of falls as well as the time of occurrence of each fall will be recorded for every subject

  • Time to major disease milestones [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    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)

  • Functional Outcomes assessment [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    Two assessments will be completed to observe the changes in the ability of the subject to perform usual day-to-day activities during the study: 1. Physician Assessment of Daily Living -by the principal investigator, treating physician or suitable proxy who interacts with the subject/parent/caregiver at the corresponding clinic visit, and 2. Functional Outcomes Survey - by the family/caregivers who attends the scheduled clinic visit.

  • Plasma concentration of drisapersen - continuous dosing regimen [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40 and 48 ] [ Designated as safety issue: No ]
  • Plasma concentration of drisapersen - intermittent dosing regimen [ Time Frame: Weeks 0, 7, 12, 19, 24, 31, 36 and 43 ] [ Designated as safety issue: No ]

Estimated Enrollment: 23
Study Start Date: May 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Primary Continuous Dosing Arm
Subjects will receive drisapersen 6 mg/kg as SC injection(s) once a week, continuously throughout their duration of participation
Drug: Drisapersen
Drisapersen will be supplied as 3 mL (milliliter) vials containing 1 mL sterile solution of 200 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
Experimental: Alternate Intermittent Dosing Arm
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
Drisapersen will be supplied as 3 mL (milliliter) vials containing 1 mL sterile solution of 200 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

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 citizens 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 citizens 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. Subjects are required to withdraw from DMD114349 to participate in this study

  • 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
  • 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)

Exclusion Criteria:

  • Subject had a serious adverse experience or who met safety stopping criteria that remains unresolved from studies DMD115501, 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
  • Current or anticipated participation in any other investigational clinical studies
  • 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)
  • Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction <45% at Screening, the investigator should discuss inclusion of subject in the study with the medical monitor
  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: NCT01803412

Sponsors and Collaborators
Prosensa Therapeutics
Investigators
Study Director: Prosensa Clinical Trials Prosensa Therapeutics
  More Information

No publications provided

Responsible Party: Prosensa Therapeutics
ClinicalTrials.gov Identifier: NCT01803412     History of Changes
Other Study ID Numbers: 115501
Study First Received: February 28, 2013
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Prosensa Therapeutics:
GSK2402968
open-label extension
safety
drisapersen
Duchenne Muscular Dystrophy
tolerability
Quality of Life

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on August 25, 2014