Clinical Trials Register

Summary
EudraCT Number:	2018-000975-34
Sponsor's Protocol Code Number:	WVE-DMDX51-002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
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

2018-000975-34

A.3

Full title of the trial

A Multicenter, Open-Label Extension Study of WVE-210201 in Patients
previously enrolled in WVE-DMDX51-001

Studio di estensione in aperto, multicentrico su WVE 210201 in pazienti precedentemente arruolati nello studio WVE-DMDX51-001

A.3.1

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

A Study of WVE-210201 in Patients previously enrolled in WVE-DMDX51001

Studio su WVE-210201 in pazienti precedentemente arruolati nello studio WVE-DMDX51-001

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

WVE-DMDX51-002

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	WAVE LIFE SCIENCES USA 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	Wave Life Sciences Ltd.
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	Bruno Rocton
B.5.3	Address:
B.5.3.1	Street Address	1-2 Crown Walk, Jewry Street
B.5.3.2	Town/ city	Winchester, Hampshire
B.5.3.3	Post code	SO23 8BB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441932563375
B.5.5	Fax number	00441932563375
B.5.6	E-mail	bruno.rocton@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.2.5	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/3/18/2051 - EMA/OD/032/18
D.3 Description of the IMP
D.3.1	Product name	WVE-210201
D.3.2	Product code	[WVE-210201]
D.3.4	Pharmaceutical form	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	WVE-210201
D.3.9.1	CAS number	2142024-01-7
D.3.9.2	Current sponsor code	WVE-210201
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	20
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

Duchenne muscular dystrophy

Distrofia muscolare di Duchenne

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] - Nervous System Diseases [C10]

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

To evaluate the safety and tolerability of WVE-210201

Valutare la sicurezza e la tollerabilità di WVE-210201

E.2.2

Secondary objectives of the trial

-To evaluate the effect of WVE-210201 treatment -To evaluate the concentration of WVE-210201 in plasma following treatment with WVE-210201
-To evaluate the concentration of WVE-210201 in urine following treatment with WVE-210201

-Valutare l’effetto del trattamento con WVE-210201 sulla produzione di distrofina
-Valutare la concentrazione di WVE-210201 nel plasma a seguito del trattamento con WVE-210201
-Valutare la concentrazione di WVE-210201 nelle urine a seguito del trattamento con WVE-210201

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient and/or parent or legal guardian must have the ability and be willing to provide written informed consent/minor assent prior to any
study-related procedures.
2. Patient successfully completed the Phase 1 study with WVE-210201, WVE-DMDX51-001.
3. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures.
4. Stable pulmonary and cardiac function, as measured by:
a. Reproducible percent predicted forced vital capacity (FVC) =50%
b. Left ventricular ejection fraction (LVEF) >55% in patients <10 years of age and >45% in patients =10 years of age, as measured (and documented) by echocardiogram.
5. Sexually mature males must be willing to use contraception for the duration of the study, if the patient is sexually active.
6. Patient and caregivers must agree not to post any study-related information on social media

1. Il paziente e/o il genitore o il tutore legale deve avere la capacità ed essere disposto a fornire il consenso informato/assenso del minore scritto prima dell'esecuzione di qualsiasi procedura correlata allo studio.
2. Il paziente ha completato con successo lo studio di Fase 1 con WVE-210201, WVE-DMDX51-001.
3. Volontà e capacità di attenersi alle visite programmate, al programma di somministrazione del farmaco, agli esami di laboratorio, alle restrizioni e a tutte le procedure previste dallo studio.
4. Funzionalità polmonare e cardiaca stabili, come misurato mediante:
a. Percentuale riproducibile della capacità vitale forzata prevista (FVC) =50%
b. Frazione di eiezione ventricolare sinistra (LVEF) >55% nei pazienti di età <10 anni e >45% nei pazienti di età =10 anni, come misurato (e documentato) con ecocardiogramma.
5. I soggetti di sesso maschile sessualmente maturi devono essere disposti a fare uso della contraccezione per tutta la durata dello studio, se sessualmente attivi.
6. Pazienti e caregiver devono accettare di non pubblicare alcuna informazione correlata allo studio sui social media.

E.4

Principal exclusion criteria

1. Clinically significant medical finding on the physical examination other than DMD that, in the judgment of the Investigator will make the patient
unsuitable for participation in, and/or unable to complete the study procedures.
2. Other prior or ongoing medical conditions including:
a. Acute illness within Screening period;
b. Abnormal physical findings, other than those associated with musculoskeletal findings attributable to DMD.
3. Laboratory abnormality, that, in the Investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow up would be completed, or impair the assessment of study results. These include, but are not limited to:
a. Renal insufficiency;
b. Impaired hepatic function as measured by glutamate dehydrogenase
(GLDH) = 2.5x upper limit of normal (ULN) and Bilirubin = 2x ULN (or INR = 1.5x ULN;
c. Activated partial thromboplastin time [aPTT] values above the ULN;
d. Platelet count less than lower limit of normal (LLN).
e. Any evidence of clinically significant structural or functional heart abnormality would prohibit participation in this study.
f. Troponin I value above 2x ULN
4. Parent or legal guardian is directly or indirectly involved in the conduct and administration of this study as an Investigator, subinvestigator,
study coordinator, or other study staff member, or the patient is a first-degree family member, significant other, or relative residing
with one of the above persons involved directly or indirectly in the study.

1. Risultato medico clinicamente significativo diverso da DMD all’esame obiettivo che, a giudizio dello sperimentatore, renderà il paziente inadatto alla partecipazione e/o non in grado di completare le procedure dello studio.
2. Altre condizioni mediche precedenti o in corso tra cui:
a. Malattia acuta entro 28 giorni dalla Visita di screening;
b. Risultati dell'esame obiettivo anomali, diversi da quelli associati a esiti muscolo-scheletrici attribuibili alla DMD.
3. Anomalie di laboratorio che, a giudizio dello sperimentatore, potrebbero compromettere la sicurezza del paziente o rendere improbabile il completamento del ciclo di trattamento o il follow-up. Tali fattori comprendono, a titolo esemplificativo ma non esaustivo, i seguenti:
a. Insufficienza renale;
b. Funzionalità epatica compromessa, rilevata da glutammato deidrogenasi (GLDH) =2,5 volte il limite superiore della norma (ULN) e bilirubina =2x ULN (o INR =1,5 x ULN);
c. Valori del tempo di tromboplastina parziale attivata (aPTT) al di sopra dell’ULN;
d. Conta delle piastrine più bassa del limite inferiore della norma (LLN).
e. Un'evidenza di anomalia cardiaca strutturale o funzionale clinicamente significativa vieterebbe la partecipazione a questo studio
f. Valore della troponina I superiore a 2x ULN
4. Genitore o tutore legale direttamente o indirettamente coinvolto nella conduzione e gestione del presente studio in qualità di sperimentatore, assistente sperimentatore, coordinatore dello studio o altro membro dello staff di ricerca oppure il paziente è un parente di primo grado, partner, o parente residente presso una delle suddette persone coinvolte direttamente o indirettamente nello studio.

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability of WVE-210201 as assessed by the number of patients with adverse events (AEs), severity of AEs, number of patients
with serious adverse events (SAEs), and the number of patients who withdraw due to AEs.

Sicurezza e tollerabilità di WVE-210201 valutate in base al numero di pazienti con eventi avversi (AE), alla gravità degli AE, al numero di pazienti con eventi avversi seri (SAE), e al numero di pazienti che si ritirano a causa di AE.

E.5.1.1

Timepoint(s) of evaluation of this end point

During study treatment - week 1 to week 13

Durante il trattamento in studio - dalla settimana 1 alla settimana 13

E.5.2

Secondary end point(s)

1. Dystrophin level assessed by Western blot muscle biopsy
2. Concentration of WVE-210201 in plasma at predefined time points -sett. 1, 2, 24, 48, 84
3. Concentration of WVE-210201 in urine at predefined time points -sett. 1

1. Livello di distrofina valutato mediante Western blot su biopsia muscolare
2. Concentrazione di WVE-210201 nel plasma in momenti temporali predefiniti
3. Concentrazione di WVE-210201 nelle urine in momenti temporali predefiniti

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Dystrophin level assessed by Western blot of muscle biopsy - open biopsy at baseline and after 22 weeks of dosing at the selected level; needle biopsy at week 94

2. Concentration of WVE-210201 in plasma at predefined time points - wk1, 2, 24, 48, 84

3. Concentration of WVE-210201 in urine at predefined time points -
wk1

1. Livello di distrofina valutato mediante Western blot su biopsia muscolare; biopsia a cielo aperto alla baseline e dopo 22 settimane di somministrazione della dose al livello selezionato; agobiopsia alla settimana 94
2. Concentrazione di WVE-210201 nel plasma in momenti temporali predefiniti - sett1, sett5
3. Concentrazione di WVE-210201 nelle urine in momenti temporali predefiniti - sett1, sett2, sett5,

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Open-Label Extension Study of WVE-210201 in Patients previously enrolled in WVEDMDX51-001

Studio di estensione in aperto su WVE-210201 in pazienti precedentemente arruolati nello studio WVE-

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

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

Canada

United States

Belgium

France

Italy

Netherlands

United Kingdom

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.1.1.1

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:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

Children aged =5 and =18 years at randomization in the WVE-DMDX51001 study

Bambini di età =5 e =18 anni al momento della randomizzazione nello studio WVE-DMDX51- 001

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

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 participation in the trial, if applicable, patients will be treated with the current standard therapy.

Dopo la partecipazione alla sperimentazione, se applicabile, i pazienti saranno trattati con l'attuale terapia standard.

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

2018-10-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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IMP with orphan designation in the indication
Orphan Designation Number:
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