Extension Study of Drisapersen in DMD Subjects
Primary Purpose
Duchenne Muscular Dystrophy
Status
No longer available
Phase
Locations
International
Study Type
Expanded Access
Intervention
Drisapersen
Sponsored by
About this trial
This is an expanded access trial for Duchenne Muscular Dystrophy focused on measuring DMD, Duchenne Muscular Dystrophy, Drisapersen, Kyndrisa, exon-skipping, exon-51, BMN-051-302, 051-302
Eligibility Criteria
Inclusion Criteria:
- 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:
- 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.
- Subjects with DMD mutation/deletion within the dystrophin gene and correctable by drisapersen-induced DMD exon 51 skipping.
- 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.
- 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.
- 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).
- 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:
- 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.
- 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.
- 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.
- 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)
- 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.
- 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.
Sites / Locations
- Kennedy Krieger Institute
- IMAI Research
- Royal Children's Hosital, Children's Neuroscience Centre
- Institute for Neuromuscular Research
- Queen Fabiola Children's University Hospital
- Universitair Ziekenhuis Gent, Afdeling Neurologie
- Universitair Ziekenhuis Gasthuisberg
- Hôpital de La Citadelle, Centre de référence des Maladies
- MHAT "Alexandrovska
- Detska Nemocnice
- FN Motol
- CHU de Nantes - Hôtel Dieu
- Hopital Armand Trousseau
- Centre hospitalier de Pau
- CHU de Toulouse - Hôpital des Enfants
- Dr. von Haunersches Kinderspital
- Universitaetsklinikum Essen
- Universitaetsklinikum Freiburg
- Hadassah, Hebrew University Medical Center
- Azienda Universitaria Ospedaliera
- IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
- IRCCS Ospedale Pediatrico Bambino Gesù
- Fondazione IRCCS Policlinico Gemelli
- Kobe University Hospital
- Kumamoto University Hospital
- National Hospital Organization
- National Center Hospital of Neurology and Psychiatry
- Seoul National University Children's Hospital
- Leiden University Medical Center
- UMCN St. Radboud
- Oslo Universitetssykehus
- SPCSK Uniwersytet Medyczny w
- Moscow Pediatrics and Children
- Hospital Sant Joan de Deu
- Hospital Infantil La Paz
- Hospital Universitari la Fe
- Kaohsiung Medical University Hospital
- Hacettepe Children's Hospsital
- UCL Institute of Child Health
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT02636686
First Posted
December 9, 2015
Last Updated
January 19, 2018
Sponsor
BioMarin Pharmaceutical
1. Study Identification
Unique Protocol Identification Number
NCT02636686
Brief Title
Extension Study of Drisapersen in DMD Subjects
Official Title
An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Drisapersen in Subjects With Duchenne Muscular Dystrophy.
Study Type
Expanded Access
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
No longer available
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical
4. Oversight
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
Keywords
DMD, Duchenne Muscular Dystrophy, Drisapersen, Kyndrisa, exon-skipping, exon-51, BMN-051-302, 051-302
7. Study Design
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Drisapersen
Other Intervention Name(s)
PRO051
Intervention Description
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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:
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.
Subjects with DMD mutation/deletion within the dystrophin gene and correctable by drisapersen-induced DMD exon 51 skipping.
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.
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.
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).
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:
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.
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.
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.
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)
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Derry Ridgway, MD
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
IMAI Research
City
Buenos Aires
ZIP/Postal Code
C1425AWC
Country
Argentina
Facility Name
Royal Children's Hosital, Children's Neuroscience Centre
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Institute for Neuromuscular Research
City
Westmead
ZIP/Postal Code
2145
Country
Australia
Facility Name
Queen Fabiola Children's University Hospital
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent, Afdeling Neurologie
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Universitair Ziekenhuis Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Hôpital de La Citadelle, Centre de référence des Maladies
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
MHAT "Alexandrovska
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Detska Nemocnice
City
Brno
ZIP/Postal Code
613 00
Country
Czechia
Facility Name
FN Motol
City
Praha 5
Country
Czechia
Facility Name
CHU de Nantes - Hôtel Dieu
City
Nantes cedex 01
ZIP/Postal Code
44093
Country
France
Facility Name
Hopital Armand Trousseau
City
Paris Cedex 12
ZIP/Postal Code
75571
Country
France
Facility Name
Centre hospitalier de Pau
City
Pau
ZIP/Postal Code
64000
Country
France
Facility Name
CHU de Toulouse - Hôpital des Enfants
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Dr. von Haunersches Kinderspital
City
Bayern
State/Province
Muenchen
ZIP/Postal Code
80337
Country
Germany
Facility Name
Universitaetsklinikum Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitaetsklinikum Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Hadassah, Hebrew University Medical Center
City
Jerusalem
ZIP/Postal Code
91240
Country
Israel
Facility Name
Azienda Universitaria Ospedaliera
City
Messina
ZIP/Postal Code
98125
Country
Italy
Facility Name
IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
IRCCS Ospedale Pediatrico Bambino Gesù
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Fondazione IRCCS Policlinico Gemelli
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
Kobe University Hospital
City
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Kumamoto University Hospital
City
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
National Hospital Organization
City
Saitama
ZIP/Postal Code
349-0196
Country
Japan
Facility Name
National Center Hospital of Neurology and Psychiatry
City
Tokyo
Country
Japan
Facility Name
Seoul National University Children's Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
UMCN St. Radboud
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Oslo Universitetssykehus
City
Oslo
ZIP/Postal Code
0027
Country
Norway
Facility Name
SPCSK Uniwersytet Medyczny w
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Moscow Pediatrics and Children
City
Moscow
ZIP/Postal Code
125412
Country
Russian Federation
Facility Name
Hospital Sant Joan de Deu
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Infantil La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitari la Fe
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Kaohsiung Medical University Hospital
City
Kaohsiung
ZIP/Postal Code
80708
Country
Taiwan
Facility Name
Hacettepe Children's Hospsital
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
UCL Institute of Child Health
City
London
ZIP/Postal Code
WC1N 1EH
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Extension Study of Drisapersen in DMD Subjects
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