Clinical Trials Register

Summary
EudraCT Number:	2015-001955-54
Sponsor's Protocol Code Number:	BMN-051-302
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-08-18
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2015-001955-54

A.3

Full title of the trial

An open-label extension study of the long-term safety, tolerability and efficacy of drisapersen in subjects with Duchenne Muscular Dystrophy.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical study to provide drisapersen (study medication) to patients with Duchenne disease (muscular disease) and to assess the safety, tolerability and effect by giving the medication long term.

A.3.2

Name or abbreviated title of the trial where available

Drisapersen extension study

A.4.1

Sponsor's protocol code number

BMN-051-302

A.5.4

Other Identifiers

Name:

Duchenne Muscular Dystrophy

Number:

DMD

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	BioMarin Pharmaceutical Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	BioMarin Pharmaceutical Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	BioMarin Pharmaceutical Inc
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	105 Digital Drive
B.5.3.2	Town/ city	Novato
B.5.3.3	Post code	94949
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrials@bmrn.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/599
D.3 Description of the IMP
D.3.1	Product name	Drisapersen
D.3.2	Product code	Drisapersen
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	drisapersen
D.3.9.2	Current sponsor code	PRO051
D.3.9.3	Other descriptive name	DRISAPERSEN SODIUM
D.3.9.4	EV Substance Code	SUB177199
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/599
D.3 Description of the IMP
D.3.1	Product name	Drisapersen
D.3.2	Product code	Drisapersen
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	drisapersen
D.3.9.2	Current sponsor code	PRO051
D.3.9.3	Other descriptive name	DRISAPERSEN SODIUM
D.3.9.4	EV Substance Code	SUB177199
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	140/0.7
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Duchenne Muscular Dystrophy (DMD)

E.1.1.1

Medical condition in easily understood language

Duchenne disease, muscle weakness

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10013801
E.1.2	Term	Duchenne muscular dystrophy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the long-term safety and tolerability of subcutaneous or intravenous drisapersen in subjects with DMD correctable by drisapersen-induced DMD exon 51 skipping who have previously participated in an eligible study.

E.2.2

Secondary objectives of the trial

• To evaluate the long-term efficacy of subcutaneous drisapersen at a dose of 6 mg/kg/week.
• To evaluate the long-term impact on functional outcomes of continued treatment with drisapersen.
• To evaluate the long-term safety and efficacy of an intermittent dosing option in those subjects unable to tolerate drisapersen 6 mg/kg/week.
• To evaluate the long-term safety and efficacy of an intravenous dosing option in those subjects unable to tolerate subcutaneous administration of drisapersen.

E.2.3

Trial contains a sub-study

E.3

Principal 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:
a. 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.
2. Subjects with DMD mutation/deletion within the dystrophin gene and correctable by drisapersen-induced DMD exon 51 skipping.
3. Male subjects age > or =5 with DMD in whom the investigator considers treatment with drisapersen is likely to lead to improvement or prevent worsening of the condition.
4. 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.
5. 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).
6. Able to give informed assent and/or consent in writing by the subject and/or parent(s)/legal guardian (according to local regulations).

E.4

Principal 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.

E.5 End points

E.5.1

Primary end point(s)

Study Endpoints/Assessments

Safety Variables:
• Incidence and severity of adverse events
• Vital signs
• ECG parameters
• Echocardiogram
• Injection Site Reactions
• Safety haematology and biochemistry parameters including non-standard parameters such as coagulation parameters (in particular activated partial thromboplastin time [aPTT]), serum cystatin C, Complement Factor C3, haptoglobin, fibrinogen, high-sensitivity C-reactive protein (hsCRP)
• Urinalysis (including quantitative protein and creatinine and their ratio)

Efficacy Variables:
Ambulant subjects
• Muscle function using 6 minute walking distance (6MWD) test.
• North Star Ambulatory Assessment.

All subjects
• Pulmonary function (forced expiratory volume in the 1st second of exhalation [FEV1], forced vital capacity [FVC]). In addition, at selected sites, Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP) will be assessed.
• Time to major disease milestones (e.g. loss of ambulation, night time ventilation)
• Performance Upper Limb (PUL)
• Patient Reported Outcome Measures (PODCI and EQ-5D-5L)
• MRI (at selected centers)

E.5.1.1

Timepoint(s) of evaluation of this end point

End of study

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Austria

Belarus

Belgium

Brazil

Bulgaria

Chile

Czech Republic

Denmark

France

Germany

Hungary

Israel

Italy

Japan

Korea, Republic of

Netherlands

Norway

Poland

Portugal

Russian Federation

Spain

Switzerland

Taiwan

Turkey

Ukraine

United Kingdom

United States

Uruguay

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

220

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

112

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

103

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

young patients starting 5 years and older.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

190

F.4.2.2

In the whole clinical trial

220

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

BioMarin wishes to provide re-access to drisapersen for subjects who previously participated in drisapersen clinical studies and who are not able to participate in any ongoing drisapersen studies in their country, until such time as drisapersen may be available commercially in their country.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-10-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-01-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-09

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