Extension Study of Drisapersen in DMD Subjects

An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Drisapersen in Subjects With Duchenne Muscular Dystrophy.

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.

Study Overview

• Status: No longer available
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Drisapersen

Detailed 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.

• Study Type: Expanded Access
• Expanded Access Type: Treatment IND/Protocol

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425AWC
    • IMAI Research
• Australia
  • Westmead, Australia, 2145
    • Institute for Neuromuscular Research
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hosital, Children's Neuroscience Centre
• Belgium
  • Brussels, Belgium, 1020
    • Queen Fabiola Children's University Hospital
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent, Afdeling Neurologie
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Gasthuisberg
  • Liege, Belgium, 4000
    • Hôpital de La Citadelle, Centre de référence des Maladies
• Bulgaria
  • Sofia, Bulgaria, 1431
    • MHAT "Alexandrovska
• Czechia
  • Brno, Czechia, 613 00
    • Detska Nemocnice
  • Praha 5, Czechia
    • FN Motol
• France
  • Nantes cedex 01, France, 44093
    • CHU de Nantes - Hotel Dieu
  • Paris Cedex 12, France, 75571
    • Hopital Armand Trousseau
  • Pau, France, 64000
    • Centre Hospitalier de Pau
  • Toulouse cedex 9, France, 31059
    • CHU de Toulouse - Hôpital des Enfants
• Germany
  • Essen, Germany, 45122
    • Universitaetsklinikum Essen
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Muenchen
    • Bayern, Muenchen, Germany, 80337
      • Dr. Von Haunersches Kinderspital
• Israel
  • Jerusalem, Israel, 91240
    • Hadassah, Hebrew University Medical Center
• Italy
  • Messina, Italy, 98125
    • Azienda Universitaria Ospedaliera
  • Milano, Italy, 20122
    • IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesù
  • Roma, Italy, 00168
    • Fondazione IRCCS Policlinico Gemelli
• Japan
  • Hyogo, Japan, 650-0017
    • Kobe University Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Saitama, Japan, 349-0196
    • National Hospital Organization
  • Tokyo, Japan
    • National Center Hospital of Neurology and Psychiatry
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Children's Hospital
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
  • Nijmegen, Netherlands, 6525 GA
    • UMCN St. Radboud
• Norway
  • Oslo, Norway, 0027
    • Oslo Universitetssykehus
• Poland
  • Warszawa, Poland, 02-097
    • SPCSK Uniwersytet Medyczny w
• Russian Federation
  • Moscow, Russian Federation, 125412
    • Moscow Pediatrics and Children
• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Deu
  • Madrid, Spain, 28046
    • Hospital Infantil La Paz
  • Valencia, Spain, 46009
    • Hospital Universitari La Fe
• Taiwan
  • Kaohsiung, Taiwan, 80708
    • Kaohsiung Medical University Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe Children's Hospsital
• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • UCL Institute of Child Health
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Derry Ridgway, MD, BioMarin Pharmaceutical

Study record dates

Study Registration Dates

• First Submitted: December 9, 2015
• First Submitted That Met QC Criteria: December 17, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): January 24, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy; DMD; Drisapersen; Kyndrisa; exon-skipping; exon-51; BMN-051-302; 051-302
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: BMN-051-302