Clinical Trials Register

Summary
EudraCT Number:	2017-004625-32
Sponsor's Protocol Code Number:	4045-302
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-12-17
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-004625-32

A.3

Full title of the trial

Long-term, Open-label Extension Study for Patients with Duchenne Muscular Dystrophy Enrolled in Clinical Trials Evaluating Casimersen or Golodirsen

Studio di estensione in aperto, a lungo termine, per pazienti affetti da distrofia muscolare di Duchenne arruolati in sperimentazioni cliniche che valutano casimersen o golodirsen

A.3.1

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

A long-term extension study of a new investigational medicinal product for the treatment of Duchenne Muscular Dystrophy patients

Studio di estensione a lungo termine di un nuovo farmaco sperimentale per il trattamento di pazienti con distrofia muscolare di Duchenne

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

4045-302

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

A.5.4

Other Identifiers

Name:

Number:

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	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	PPD
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	3900 Paramount Parkway
B.5.3.2	Town/ city	Morrisville, NC
B.5.3.3	Post code	28560
B.5.3.4	Country	United States
B.5.4	Telephone number	00019105588912
B.5.5	Fax number	00019198828919
B.5.6	E-mail	leslie.gransden@ppdi.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.2.1.1.1	Trade name	--
D.2.1.1.2	Name of the Marketing Authorisation holder	----
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SRP-4045
D.3.2	Product code	[SRP-4045]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
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	CASIMERSEN
D.3.9.1	CAS number	1422958-19-7
D.3.9.2	Current sponsor code	SRP-4045
D.3.9.3	Other descriptive name	Phosphorodiamidate morpholino oligomer for exon 45 skipping
D.3.9.4	EV Substance Code	SUB188601
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.2.1.1.1	Trade name	---
D.2.1.1.2	Name of the Marketing Authorisation holder	---
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SRP-4053
D.3.2	Product code	[SRP-4053]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
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	GOLODIRSEN
D.3.9.1	CAS number	1422959-91-8
D.3.9.2	Current sponsor code	SRP-4053
D.3.9.3	Other descriptive name	Phosphorodiamidate morpholino oligomer for exon 53 skipping
D.3.9.4	EV Substance Code	SUB188593
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Patients with Duchenne Muscular Dystrophy Amenable to Exon 45 or 53 Skipping

Pazienti con Distrofia Muscolare di Duchenne trattabile con lo Skipping dell'esone 45 o 53

E.1.1.1

Medical condition in easily understood language

Duchenne muscular dystrophy

Distrofia muscolare di Duchenne

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	20.0
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

The primary objective of the study is to evaluate the safety and tolerability of long-term treatment with 30 mg/kg of casimersen or golodirsen.

Valutare la sicurezza e la tollerabilità del trattamento a lungo termine con 30 mg/kg di casimersen o golodirsen.

E.2.2

Secondary objectives of the trial

• To evaluate changes in physical functioning with long-term treatment with 30 mg/kg of casimersen or golodirsen.
• To evaluate changes in pulmonary function with long-term treatment with 30 mg/kg of casimersen or golodirsen.
• To evaluate immunogenicity of long-term treatment with 30 mg/kg casimersen or golodirsen.

• Valutare le variazioni nella funzionalità fisica con il trattamento a lungo termine con 30 mg/kg di casimersen o golodirsen.
• Valutare le variazioni nella funzionalità polmonare con il trattamento a lungo termine con 30 mg/kg di casimersen o golodirsen.
• Valutare l'immunogenicità del trattamento a lungo termine con 30 mg/kg casimersen o golodirsen.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Completed a clinical trial evaluating casimersen or golodirsen, per protocol.
2. If sexually active, agrees to use a male condom during such activity for the entire duration of the study and for 90 days after the last dose of study drug. The sexual partner must also use a medically acceptable
form of contraceptive (eg, female oral contraceptives) during this time frame.
3. Is able to understand and comply with all the study requirements and, if under 18 years of age, has as (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with all the study requirements.
4. Is willing and legally able to provide written informed assent and/or consent, or, if not legally able to provide written informed assent and/or consent, has (a) parent(s) or legal guardian(s) who is (are) willing and legally able to provide written informed assent and/ or consent for the patient to participate in the study.
5. Is between 7 and 23 years of age, inclusive, at enrollment

1. Aver completato una sperimentazione clinica di valutazione di casimersen o golodirsen, secondo il protocollo.
2. Se sessualmente attivo, accettare di utilizzare un preservativo maschile durante tale attività per tutta la durata dello studio e per 90 giorni dopo l'ultima dose di farmaco in studio. La partner sessuale deve inoltre utilizzare una forma di contraccezione clinicamente accettabile (ad es. contraccettivo femminile orale) durante questo periodo di tempo.
3. Essere in grado di comprendere e rispettare tutti i requisiti dello studio e, se di età inferiore a 18 anni, avere (a) un genitore/i genitori o un tutore legale/tutori legali in grado di comprendere e rispettare tutti i requisiti dello studio.
4. Essere disposto e legalmente in grado di fornire consenso informato e/o assenso scritto, o, se non legalmente in grado di fornire consenso informato e/o assenso, ha genitori o tutori legali che sono disponibili e legalmente in grado di fornire consenso informato scritto e/o assenso affinché il paziente possa partecipare allo studio.
5. È tra 7 e 23 anni, incluso, all'atto dell'iscrizione

E.4

Principal exclusion criteria

1. Any medical condition that could, in the Investigator's opinion, adversely affect the safety of the patient, make it unlikely that the course of treatment would be completed, or impair the assessment of study results.
2. Any patient who, in the Investigator's opinion, seems unable/unwilling to comply with the study procedures.
3. Treatment with any investigational therapies at the time of consent or within 6 months prior to dosing if there was an unexpected gap in treatment.

E 1. Qualsiasi condizione medica che, a giudizio dello sperimentatore, pregiudichi la sicurezza del paziente, renda improbabile il completamento del ciclo di trattamento o comprometta la valutazione dei risultati dello studio.
E 2. Qualsiasi paziente che, a giudizio dello sperimentatore, non sembri disposto/in grado di rispettare le procedure dello studio.
E 3. Trattamento con qualsiasi terapia sperimentale al momento del consenso o entro 6 mesi prima della somministrazione della dose in caso di intervallo imprevisto nel trattamento.

E.5 End points

E.5.1

Primary end point(s)

Patient incidence of serious adverse events (SAEs)

Incidenza di eventi avversi seri (SAE) nei pazienti

E.5.1.1

Timepoint(s) of evaluation of this end point

continuous

E.5.2

Secondary end point(s)

• 6-minute walk test (6MWT)
• Performance of the Upper Limb (PUL)
• North Star Ambulatory Assessment (NSAA)
• Loss of ambulation (LOA) by continued with wheelchair (CWU)
• Pulmonary function tests (PFTs)
• Need for assisted ventilation
• Percentage of patients who develop anti-dystrophin, anti-casimersen, or anti-golodirsen antibodies

• Test del cammino in 6 minuti (6MWT)
• Prestazioni degli arti superiori (PUL)
• Valutazione della deambulazione North Star (NSAA)
• Perdita di deambulazione (LOA) continuando con la sedia a rotelle (CWU)
• Test della funzionalità polmonare (PFT)
• Necessità di ventilazione assistita
• Percentuale di pazienti che sviluppano anticorpi anti-distrofina, anti-casimersen o anti-golodirsen

E.5.2.1

Timepoint(s) of evaluation of this end point

6MWT, PUL, NSAA, PFTs: Screening, Week 24, 48, 72, 96, 120, 144
LOA: Week 60, 72, 84, 96, 108, 120, 132, 144
Need for assisted ventilation: continuous
Immunogenicity*: Screening, Week 1, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144
*Patients who previously participated in 4045-101 or 4053-101 do not need to have immunogenicity testing at Weeks 1, 4 and 8

6MWT, PUL, NSAA, PFTs, CWU: Screening, Week 24, 48, 72, 96, 120, 144
LOA: Week 60, 72, 84, 96, 108, 120, 132, 144
Need for assisted ventilation: continuous
Immunogenicity*: Screening, Week 1, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144
*Patients who previously participated in 4045-101 or 4053-101 do not need to have immunogenicity testing at Weeks 1, 4 and 8

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

E.8.1.1

Randomised

E.8.1.2

Open

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

Information not present in EudraCT

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

Australia

Canada

Israel

United States

Belgium

Czechia

Finland

France

Germany

Ireland

Italy

Poland

Spain

Sweden

United Kingdom

E.8.7

Trial has a data monitoring committee

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.1.1.1

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:

104

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

130

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

This study is intended to be conducted with minors and will include male patients from 2 years old, and adults.

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

133

F.4.2.2

In the whole clinical trial

260

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)

It is anticipated by the Sponsor that the clinical study 4045-302 evaluating casimersen and golodirsen will conclude prior to these products being commercially available. If this is the case, the sponsor may consider to extend the study to continuously provide the
treatment option for those DMD patients.

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

2018-08-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-19

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

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IMP with orphan designation in the indication
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