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

About

Brief Summary

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 (LTE) period (192 weeks).

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1/Phase 2

Eligibility

Gender

Male

Healthy Volunteers

No

Minimum Age

4 Years

Maximum Age

16 Years

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 enrollment.
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.