ICH GCP - EU Clinical trials Registry - 2021-005478-24 (IE)

Klinische Studien Nct Page

Summary
EudraCT Number:	2021-005478-24
Sponsor's Protocol Code Number:	DYNE251-DMD-201
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2022-08-24
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

A. Protocol Information

A.1

Member State Concerned

Ireland - HPRA

A.2

EudraCT number

2021-005478-24

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and Pharmacokinetics of DYNE-251 Administered to Participants with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

A.3.1

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

Study of DYNE-251 in Participants with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

A.4.1

Sponsor's protocol code number

DYNE251-DMD-201

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	Dyne 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	Dyne 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	Dyne Therapeutics, Inc
B.5.2	Functional name of contact point	Dyne Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	1560 Trapelo Rd
B.5.3.2	Town/ city	Waltham, MA
B.5.3.3	Post code	02451
B.5.3.4	Country	United States
B.5.4	Telephone number	1781317-1919
B.5.6	E-mail	clinicaltrials@dyne-tx.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	DYNE-251
D.3.2	Product code	DYNE-251
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	NA
D.3.9.1	CAS number	2725863-42-1
D.3.9.2	Current sponsor code	DYNE-251
D.3.9.3	Other descriptive name	Fragment antibody targeting human TfR1 conjugated to phosphorodiamidate morpholino oligomer
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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
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

Muscular disease causing progressive loss of skeletal, pulmonary, cardiac and muscle function

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

To evaluate the safety and tolerability of multiple IV doses of DYNE-251 administered to participants with DMD

To evaluate dystrophin protein levels in muscle tissue following multiple IV doses of DYNE-251 administered to participants with DMD

E.2.2

Secondary objectives of the trial

To evaluate the effects on muscle tissue exon skipping, percent dystrophin-positive fibers (PDPFs), and blood creatine kinase (CK) following multiple IV doses of DYNE-251 administered to participants with DMD

To evaluate muscle function following multiple IV doses of DYNE-251 administered to participants with DMD

To evaluate plasma and muscle tissue PK following multiple IV doses of DYNE-251
administered to participants with DMD

To evaluate the immunogenicity of multiple IV doses of DYNE-251 administered to participants with DMD

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age 4 to 16 years inclusive, at the time of informed consent/assent.
• Male with a confirmed DMD mutation in the dystrophin gene characterized by exon deletion amenable to exon 51 skipping.
• Upper extremity muscle group that is amenable to muscle biopsy.
• Brooke Upper Extremity Scale score of 1 or 2.
• Ambulatory or non-ambulatory. A non-ambulatory participant must have been non-ambulatory for <2 years before enrolment.
• Receiving a stable dosage of glucocorticoids for at least 12 weeks prior to the start of study drug administration.
• Left ventricular ejection fraction of ≥50% by echocardiogram or ≥55% by cardiac magnetic resonance imaging (MRI).

E.4

Principal exclusion criteria

• Uncontrolled clinical symptoms and signs of congestive heart failure (CHF).
• Any change in prophylaxis/treatment for CHF within 3 months prior to the start of study treatment.
• History of major surgical procedure within 12 weeks prior to the start of study drug administration or an expectation of a major surgical procedure during the study.
• Requirement of daytime ventilator assistance.
• Percent predicted FVC <40 % (applies only for participants who are age ≥7 years).
• Receipt of eteplirsen, or alternative exon-skipping/dystrophin-modifying therapy, within 12 weeks of randomization.
• Receipt of non-exon skipping investigational drug within 4 months before the start of study drug administration.
• Receipt of gene therapy at any time.

E.5 End points

E.5.1

Primary end point(s)

1. Number and proportion of participants with treatment-emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), TEAEs considered related to study drug, and TEAEs leading to discontinuation from study drug and discontinuation from the study.
2. Change from Baseline in dystrophin protein levels in muscle tissue as determined by Western blot analysis at Week 25

E.5.1.1

Timepoint(s) of evaluation of this end point

1. All visits from screening to end of study
2. Screening and week 25 visit

E.5.2

Secondary end point(s)

1. Change from Baseline in muscle tissue exon 51 skipping levels at Week 25
2. Change from Baseline in muscle tissue PDPF at Week 25
3. Change from Baseline in blood CK levels up to Week 145
4. Change from Baseline in North Star Ambulatory Assessment (NSAA) total score in ambulatory participants up to Week 145
5. Change from Baseline in time to rise from floor in ambulatory participants up to Week 145
6. Change from Baseline in 10-meter run/walk (10-MRW) time in ambulatory participants up to Week 145
7. Change from Baseline in performance upper limb (PUL) scale Version 2.0 score up to Week 145
8. Change from Baseline in percent predicted forced vital capacity (FVC) up to Week 145
9. Change from Baseline in stride velocity 95th centile (SV95C) up to Week 145
10. Maximum observed drug concentration (Cmax)
11. Time to maximum concentration (tmax)
12. Area under the concentration-time curve (AUC) from hour 0 to the last measurable concentration (AUCtlast)
13. AUC extrapolated to infinity (AUC∞)
14. Apparent terminal elimination rate constant (λZ)
15. Apparent terminal elimination half-life (t½)
16. Plasma clearance (CL)
17. Volume of distribution at the terminal phase (Vz), if appropriate
18. Volume of distribution at steady state (Vss), if appropriate
19. Tissue phosphorodiamidate morpholino oligomer (PMO) concentration
20. Incidence of antidrug antibodies (ADAs)

E.5.2.1

Timepoint(s) of evaluation of this end point

- For endpoints 1 and 2: Screening and week 25 visit
- For endpoint 3: Screening, D1/pre-dose, D3, D8, W5, W9, W13, W17, W21, W25, W37, W29, W33, W41, W45, W49, W53, W57, W65, W69, W77, W81, W89, W93, W101, W105, W113, W117, W125, W129, W137, W141, W61, W85, W109, W133, W73, W121, W97, W145
- For endpoints 4 through 8: Screening, W13, W25, W37, W49, W73, W121, W97, W145
- For endpoints 9 through 17: D1/Pre-dose, D1/EOI, D1/15min-post, D1/1h-post, D1/4h-post, D1/8h-post, D1/12h-post, D2, D3, D8, W5, W25, W49, W97, W145
- For endpoint 18: Screening and week 25
- For endpoint 19: Screening, W5, W9, W13, W17, W21, W25, W37, W29, W33, W41, W45, W49, W53, W57, W65, W69, W77, W81, W89, W93, W101, W105, W113, W117, W125, W129, W137, W141, W61, W85, W109, W133, W73, W121, W97, W145

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Ireland

Australia

Belgium

Canada

Italy

Spain

United Kingdom

United States

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

Number of subjects for this age range:

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

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

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)

Open label study/registry.

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

2022-10-28

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

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