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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dyne Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

6 Jan 2023 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Dyne Therapeutics, Inc.

External identifiers

EU CT number

2023-510351-31-00

EudraCT number

2021-005478-24

ClinicalTrials.gov

NCT05524883

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

"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 "

Secondary objectives 4

1. 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
2. To evaluate muscle function following multiple IV doses of DYNE-251 administered to participants with DMD
3. To evaluate plasma and muscle tissue PK following multiple IV doses of DYNE-251 administered to participants with DMD
4. To evaluate the immunogenicity of multiple IV doses of DYNE-251 administered to participants with DMD

Conditions and MedDRA coding

Duchenne muscular dystrophy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Age 4 to 16 years inclusive, at the time of informed consent/assent. • Male with a confirmed diagnosis of DMD and with a 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).

Exclusion criteria 1

1. • 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/dystrophinmodifying 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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

Secondary endpoints 9

1. Muscle Tissue Endpoints: Cohorts dosed Q4W or Q8W with a second biopsy at Week 25
2. Change from Baseline at Week 25: -exon 51 skipping levels in muscle tissue -PDPF in muscle tissue -PMO concentration in muscle tissue
3. Change from baseline up to Week 145: -blood CK levels
4. Cohorts dosed Q8W with a second biopsy at Week 49 Change from Baseline at Week 49 in: -dystrophin protein levels in muscle tissue -exon 51 skipping levels in muscle tissue -PDPF in muscle tissue -PMO concentration in muscle tissue
5. Change from Baseline up to Week 145 in: -blood CK level
6. Functional Endpoints: All cohorts
7. Change from Baseline up to Week 145 in: -PUL scale V 2.0 score -%pFVC -NSAA total score, TTR, 10MRW, and SV95C in ambulatory participants
8. Plasma Endpoints: All cohorts -Cmax -tmax -AUCtlast -AUC∞ -λZ -t½ -CL -Vz and Vss, if appropriate
9. Immunogenicity Endpoint: All cohorts -Incidence of ADAs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dyne Therapeutics Inc.

Sponsor organisation

Dyne Therapeutics Inc.

Address

1560 Trapelo Road

City

Waltham

Postcode

02451-7306

Country

United States

Scientific contact point

Organisation

Dyne Therapeutics Inc.

Contact name

Dyne Clinical Trials

Public contact point

Organisation

Dyne Therapeutics Inc.

Contact name

Dyne Clinical Trials

Third parties 22

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 76 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications