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

Duchenne Muscular Dystrophy (DMD) Clinical Trial

— DELIVER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05524883
• Other study ID #: DYNE251-DMD-201
• Secondary ID: 2021-005478-24
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 12, 2022
• Est. completion date: November 2026

Study information

• Verified date: June 2024
• Source: Dyne Therapeutics
• Contact: Dyne Clinical Trials
• Phone: +1-781-317-1919
• Email: clinicaltrials[@]dyne-tx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 period (96 weeks).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: November 2026
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy (DMD)
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• DYNE-251
Administered by IV infusion
• Placebo
Administered by IV infusion

Locations

Country	Name	City	State
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	CHR Citadelle	Liège
Canada	London Health Sciences Centre	London	Ontario
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Children's and Women's Health Centre of British Columbia	Vancouver	British Columbia
Italy	Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN	Genova	Liguria
Italy	Fondazione Serena Onlus - Centro Clinico NeMO	Milan	Lombardia
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milan	Lombardia
Italy	Fondazione Policlinico Universitario A Gemelli	Rome	Lazio
Spain	Hospital Sant Joan de Déu Universidad de Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	West Yorkshire
United Kingdom	Alder Hey Children's Hospital	Liverpool	Merseyside
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Royal Victoria Infirmary	Newcastle Upon Tyne	Northumberland
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of California San Diego	La Jolla	California
United States	UCLA	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Shriners Hospitals for Children Portland	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Utah - PPDS	Salt Lake City	Utah
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Dyne Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)		Through study completion, up to Week 145
Primary	Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25		Baseline, Week 25
Secondary	Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 25 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25		Baseline, Week 25
Secondary	Change From Baseline in Muscle Tissue Percent Dystrophin-Positive Fiber (PDPF) at Week 25 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25		Baseline, Week 25
Secondary	Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 145 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25		Baseline, up to Week 145
Secondary	Change From Baseline in Dystrophin Protein Level in Muscle Tissue as Determined by Western Blot at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49		Baseline, Week 49
Secondary	Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49		Baseline, Week 49
Secondary	Change From Baseline in Muscle Tissue PDPF at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49		Baseline, Week 49
Secondary	Change From Baseline in Blood CK Levels up to Week 145 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49		Baseline, up to Week 145
Secondary	Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 145	The NSAA is a 17-item functional scale used to measure functional motor abilities in ambulant participants with DMD and monitor progression of the disease and treatment effects in each of the items. The items are graded on a 3-point scale: 0=unable to achieve independently, 1=modified method but achieves goal with no physical assistance, and 2=normal, no obvious modification of activity. Total score range is 0 to 34.	Baseline, up to Week 145
Secondary	Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 145		Baseline, up to Week 145
Secondary	Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 145		Baseline, up to Week 145
Secondary	Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 145	The PUL scale is a validated tool specifically designed for assessing upper limb function in ambulant and non-ambulant individuals with DMD. It includes an entry item to define the broad starting functional level and 22 items subdivided into 3 areas indicative of upper limb strength as, shoulder level, midlevel, and distal level. The global score is a combination of the 3 areas and ranges from 0 to 42. Lower scores indicate higher disability.	Baseline, up to Week 145
Secondary	Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 145		Baseline, up to Week 145
Secondary	Change From Baseline in Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 145		Baseline, up to Week 145
Secondary	Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax)		Through study completion, up to Week 145
Secondary	Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax)		Through study completion, up to Week 145
Secondary	Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast)		Through study completion, up to Week 145
Secondary	Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC8)		Through study completion, up to Week 145
Secondary	Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (?z)		Through study completion, up to Week 145
Secondary	Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½)		Through study completion, up to Week 145
Secondary	Total Body Clearance (CL) of DYNE-251		Through study completion, up to Week 145
Secondary	Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz)		Through study completion, up to Week 145
Secondary	Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss)		Through study completion, up to Week 145
Secondary	Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue		Through study completion, up to Week 145
Secondary	Percentage of Participants With Antidrug Antibodies (ADAs)		Through study completion, up to Week 145