Extension Study of Drisapersen in DMD Subjects

Duchenne Muscular Dystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: No longer available

Administrative data

• NCT number: NCT02636686
• Other study ID #: BMN-051-302
• Status: No longer available
• Phase: N/A
• First received: December 9, 2015
• Last updated: January 19, 2018

Study information

• Verified date: January 2018
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Expanded Access

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: No longer available
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Drisapersen
Subjects will receive 6 mg/kg of drisapersen by subcutaneous injection once weekly. If subjects have experienced an intolerable injection site reaction(s), in consultation with the investigator, the subject may be allowed intermittent injections (8 weeks on/4 weeks off) or weekly intravenous infusions of 3 or 6 mg/kg

Locations

Country	Name	City	State
Argentina	IMAI Research	Buenos Aires
Australia	Royal Children's Hosital, Children's Neuroscience Centre	Parkville	Victoria
Australia	Institute for Neuromuscular Research	Westmead
Belgium	Queen Fabiola Children's University Hospital	Brussels
Belgium	Universitair Ziekenhuis Gent, Afdeling Neurologie	Gent
Belgium	Universitair Ziekenhuis Gasthuisberg	Leuven
Belgium	Hôpital de La Citadelle, Centre de référence des Maladies	Liege
Bulgaria	MHAT "Alexandrovska	Sofia
Czechia	Detska Nemocnice	Brno
Czechia	FN Motol	Praha 5
France	CHU de Nantes - Hôtel Dieu	Nantes cedex 01
France	Hopital Armand Trousseau	Paris Cedex 12
France	Centre hospitalier de Pau	Pau
France	CHU de Toulouse - Hôpital des Enfants	Toulouse cedex 9
Germany	Dr. von Haunersches Kinderspital	Bayern	Muenchen
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Freiburg	Freiburg
Israel	Hadassah, Hebrew University Medical Center	Jerusalem
Italy	Azienda Universitaria Ospedaliera	Messina
Italy	IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena	Milano
Italy	Fondazione IRCCS Policlinico Gemelli	Roma
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Roma
Japan	Kobe University Hospital	Hyogo
Japan	Kumamoto University Hospital	Kumamoto
Japan	National Hospital Organization	Saitama
Japan	National Center Hospital of Neurology and Psychiatry	Tokyo
Korea, Republic of	Seoul National University Children's Hospital	Seoul
Netherlands	Leiden University Medical Center	Leiden
Netherlands	UMCN St. Radboud	Nijmegen
Norway	Oslo Universitetssykehus	Oslo
Poland	SPCSK Uniwersytet Medyczny w	Warszawa
Russian Federation	Moscow Pediatrics and Children	Moscow
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Hospital Infantil La Paz	Madrid
Spain	Hospital Universitari la Fe	Valencia
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Turkey	Hacettepe Children's Hospsital	Ankara
United Kingdom	UCL Institute of Child Health	London
United States	Kennedy Krieger Institute	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Czechia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  United Kingdom,