Clinical Trials Register

Summary
EudraCT Number:	2019-003374-91
Sponsor's Protocol Code Number:	SRP-9001-301
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-10-21
Trial 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

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2019-003374-91

A.3

Full title of the trial

A Phase 3 Multinational, Randomized, Double-Blind, Placebo-Controlled Systemic Gene Delivery Study to Evaluate the Safety and Efficacy of SRP-9001 in Subjects With Duchenne Muscular Dystrophy (EMBARK)

A.3.1

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

Study to Evaluate the Safety and Efficacy of SRP-9001 in Subjects With Duchenne Muscular Dystrophy

A.4.1

Sponsor's protocol code number

SRP-9001-301

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/419/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sarepta Therapeutics, 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	Sarepta Therapeutics, 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	Sarepta Therapeutics, Inc.
B.5.2	Functional name of contact point	Patient Recruitment
B.5.3	Address:
B.5.3.1	Street Address	215 First Street
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	MA 02142
B.5.3.4	Country	United States
B.5.4	Telephone number	+18887273782
B.5.6	E-mail	clinicaltrials@sarepta.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/3/20/2250
D.3 Description of the IMP
D.3.2	Product code	SRP-9001
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Delandistrogene moxeparvovec
D.3.9.1	CAS number	2305040-16-6
D.3.9.2	Current sponsor code	SRP-9001
D.3.9.3	Other descriptive name	ADENO-ASSOCIATED VIRUS SEROTYPE RH74 CONTAINING THE HUMAN MICRO-DYSTROPHIN GENE
D.3.9.4	EV Substance Code	SUB197789
D.3.10	Strength
D.3.10.1	Concentration unit	vector genomes (vg)/mL
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.33 x 10^13
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

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

E.1.1.1

Medical condition in easily understood language

Duchenne Muscular Dystrophy

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	20.1
E.1.2	Level	PT
E.1.2	Classification code	10052655
E.1.2	Term	Duchenne muscular dystrophy gene carrier
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
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 effect of SRP-9001 on physical function as assessed by the North Star Ambulatory Assessment (NSAA) score

E.2.2

Secondary objectives of the trial

• To evaluate the effect of SRP-9001 on physical function as assessed by:
o Number of skills gained or improved on the NSAA
• To evaluate micro-dystrophin expression from SRP-9001 at 12 weeks (Part 1) as measured by Western blot of biopsied muscle tissue
• To evaluate the effect of SRP-9001 on timed function tests as assessed by measuring:
o Time to rise from the floor
o 100-meter walk/run (100MWR)
o Time to ascend 4 steps
o 10-meter walk/run (10MWR)
• To evaluate the effect of SRP-9001 on stride velocity 95th centile (SV95C) as measured by a wearable device
• To evaluate subject (parent/caregiver proxy) reported Mobility and Upper Extremity Function using the Patient Reported Outcomes Measurement Information System (PROMIS®) tool
• To evaluate the safety of SRP-9001

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A subject must meet all of the following criteria to be eligible to participate in this study:
1. Is male at birth, ambulatory, and ≥ 4 to < 8 years of age at the time of randomization.
2. Has a definitive diagnosis of DMD prior to Screening based on documentation of clinical findings and prior confirmatory genetic testing using a clinical diagnostic genetic test. Genetic report must describe a frameshift deletion, frameshift duplication, premature stop ("nonsense"), canonical splice site mutation, or other pathogenic variant in the DMD gene fully contained between exons 18 to 79 (inclusive) that is expected to lead to absence of dystrophin protein.
a. Mutations between or including exons 1-17 are not eligible.
b. In-frame deletions, in-frame duplications, and variants of uncertain significance (“VUS”) are not eligible.
c. Mutations fully contained within exon 45 (inclusive) are not eligible.
3. Able to cooperate with motor assessment testing.
4. Has a NSAA score > 16 and < 29 at the Screening visit.
5. Has a time to rise from floor < 5 seconds at the Screening visit.
6. Stable daily dose of oral corticosteroids for at least 12 weeks before Screening and the dose and regimen are expected to remain constant (except for modifications to accommodate changes in weight) throughout the study.
7. Has rAAVrh74 antibody titers < 1:400 (ie, not elevated) as determined by an ELISA.
8. Subjects who are sexually active must agree to use, for the entire duration of the study, a condom and the female sexual partner must also use a medically acceptable form of birth control (eg, oral contraceptive). Refer to Appendix 1 for guidance on highly effective contraceptive methods.
9. Has (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with the study visit schedule and all other protocol requirements.
10. Is willing to provide informed assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide informed consent for the subject to participate in the study.

E.4

Principal exclusion criteria

A subject who meets any of the following criteria will be excluded from this study:
1. Has left ventricular ejection fraction < 40% on the screening ECHO or clinical signs and/or symptoms of cardiomyopathy.
2. Major surgery within 3 months prior to Day 1 or planned surgery or procedures that would interfere with the conduct of the study for any time during this study.
3. Presence of any other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for gene transfer or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the subject’s ability to comply with the protocol required testing or procedures or compromise the subject’s wellbeing, safety, or clinical interpretability.
4. Has serological evidence of current, chronic, or active human immunodeficiency virus, hepatitis C, or hepatitis B infection.
5. Has a symptomatic infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks prior to Day 1.
6. Demonstrates cognitive delay or impairment that could confound motor development in the opinion of the Investigator.
7. Treatment with any of the following therapies according to the time frames specified:
• Any time:
− Gene therapy
− Cell based therapy (eg, stem cell transplantation)
− CRISPR/Cas9, or any other form of gene editing
• Within 12 weeks of Day 1 and any time during the study:
− Use of human growth factor or vamorolone
• Within 6 months of Day 1 and any time during the study:
− Any investigational medication
− Any treatment designed to increase dystrophin expression (eg, Translarna™, EXONDYS 51™, VILTEPSO™)
8. Has received a live virus vaccine within 4 weeks or inactive vaccine within 2 weeks of the Day 1 visit or expects to receive a vaccination during the first 3 months after Day 1.
9. Has abnormal laboratory values considered clinically significant including but not limited to:
• Gamma-glutamyl transferase > 2× upper limit of normal (ULN)
• Glutamate dehydrogenase (GLDH) > 15 U/L
• Total bilirubin > ULN. Note; elevations in total bilirubin confirmed to be due to Gilbert’s syndrome are not exclusionary.
• White blood cell count > 18,500 per µl
• Platelets ≤ 150,000 per µL
10. Known hypersensitivity to SRP-9001 or any excipients of SRP-9001.
11. Family does not want to disclose subject’s study participation with general practitioner/primary care physician and other medical providers.
12. In the opinion of the Investigator, the subject is not likely to be compliant with the study protocol.

E.5 End points

E.5.1

Primary end point(s)

• Change in NSAA total score from Baseline to Week 52 (Part 1)

E.5.1.1

Timepoint(s) of evaluation of this end point

From Baseline to Week 52 (Part 1)

E.5.2

Secondary end point(s)

• Number of skills gained or improved at Week 52 (Part 1) as measured by the NSAA
• Quantity of micro-dystrophin protein expression at Week 12 (Part 1) as measured by Western Blot
• Change in time to rise from the floor from Baseline to Week 52 (Part 1)
• Change in time of 100MWR from Baseline to Week 52 (Part 1)
• Change in time to ascend 4 steps from Baseline to Week 52 (Part 1)
• Change in time of 10MWR from Baseline to Week 52 (Part 1)
• Change in SV95C from Baseline to Week 52 (Part 1)
• Change in PROMIS score in Mobility and Upper Extremity from Baseline to Week 52 (Part 1)
• Incidence of treatment-emergent adverse events
• Incidence of serious adverse events
• Incidence of adverse events of special interest
• Clinically significant changes in vital signs and physical examination findings
• Clinically significant changes in safety laboratory assessments, electrocardiograms (ECGs), and echocardiograms (ECHOs)

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Hong Kong

Taiwan

Japan

United Kingdom

United States

Belgium

France

Germany

Italy

Spain

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

Last Patient Last Visit

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:

120

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:

120

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

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

Patients ≥ 4 to < 8 years of age at the time of randomization

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

F.4.2.2

In the whole clinical trial

120

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)

After completion of the Part 2 Week 52 assessments, subjects could be enrolled into an extension study to assess long-term safety and efficacy.

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-05-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-17

P. End of Trial
P.	End of Trial Status	Ongoing

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