Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping (DELIVER)

Dyne Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Duchenne Muscular Dystrophy (DMD)

Treatments: Drug: Placebo; Drug: DYNE-251

Study type: Interventional

Funder types: Industry

Identifiers

NCT05524883

DYNE251-DMD-201

2021-005478-24 (EudraCT Number)

Details and patient eligibility

About

The primary purpose of this study is to evaluate the safety, tolerability, and dystrophin protein levels in muscle tissue following multiple intravenous (IV) doses of DYNE-251 in participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping.

The study consists of 3 periods: a multiple-ascending dose (MAD) / placebo-controlled period (24 weeks), an open-label period (24 weeks) and a long-term extension period (96 weeks).

Enrollment: 88 estimated patients

Sex: Male

Ages: 4 to 16 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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, with the expectation of maintaining a stable dose during the Placebo-Controlled and Open-Label Periods of the study (unless dose adjustment is required by weight change).
• Left ventricular ejection fraction of ≥50% by echocardiogram or ≥55% by cardiac magnetic resonance imaging (MRI).

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.

Other inclusion and exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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88 participants in 3 patient groups

Placebo-Controlled MAD Period - DYNE-251

Experimental group

Description:

DYNE-251 will be administered once every 4 weeks (Q4W) or once every 8 weeks (Q8W) over 24 weeks.

Treatment:

Drug: DYNE-251

Placebo-Controlled MAD Period - Placebo

Experimental group

Description:

Placebo will be administered Q4W or Q8W over 24 weeks.

Treatment:

Drug: Placebo

Open-Label and Long-Term Extension Period - DYNE-251

Experimental group

Description:

DYNE-251 will be administered Q4W or Q8W for up to 96 weeks after participants complete the Placebo-Controlled MAD Period of the study.

Treatment:

Drug: DYNE-251