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

March 12, 2024 updated by: Dyne Therapeutics

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

88

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 02145
        • Recruiting
        • Children's Hospital at Westmead
        • Contact:
        • Principal Investigator:
          • Michelle Lorentzos
  • Belgium
      • Gent, Belgium, 9000
        • Recruiting
        • UZ Gent
        • Contact:
      • Leuven, Belgium, 3000
      • Liège, Belgium, 4000
  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • Recruiting
        • London Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Craig Campbell, MD, MSc
      • Ottawa, Ontario, Canada, ON K1H 8L1
        • Recruiting
        • Children's Hospital of Eastern Ontario
        • Contact:
  • Italy
    • Lazio
    • Liguria
      • Genova, Liguria, Italy, 16147
        • Recruiting
        • Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN
        • Contact:
    • Lombardia
      • Milan, Lombardia, Italy, 20312
        • Recruiting
        • Ospedale San Raffaele S.r.l. - PPDS
        • Contact:
      • Milan, Lombardia, Italy, 20162
  • Spain
      • Barcelona, Spain, 8025
        • Recruiting
        • Hospital Universitario Vall d'Hebron - PPDS
        • Contact:
      • Barcelona, Spain, 8950
        • Recruiting
        • Hospital Sant Joan de Déu Universidad de Barcelona
        • Contact:
  • United Kingdom
    • Merseyside
      • Liverpool, Merseyside, United Kingdom, L12 2AP
        • Recruiting
        • Alder Hey Children's Hospital
        • Contact:
    • Northumberland
      • Newcastle Upon Tyne, Northumberland, United Kingdom, NE1 4LP
        • Recruiting
        • Royal Victoria Infirmary
        • Contact:
        • Principal Investigator:
          • Michela Guglieri, MD
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS1 3EX
  • United States
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • University of California San Diego
        • Contact:
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA
        • Contact:
          • Perry Shieh
        • Principal Investigator:
          • Perry Shieh
    • Colorado
    • Georgia
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • UMASS Memorial Medical Center
        • Contact:
    • Ohio
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Shriners Hospitals for Children Portland
        • Principal Investigator:
          • Erika Finanger, MD
        • Contact:
    • Tennessee
      • Memphis, Tennessee, United States, 38105-3678
        • Recruiting
        • St. Jude Children's Research Hospital
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 08412
        • Recruiting
        • University of Utah - PPDS
        • Principal Investigator:
          • Russell Butterfield, MD, PhD
        • Contact:
    • Virginia
      • Richmond, Virginia, United States, 23219

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 16 years (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo-Controlled MAD Period - DYNE-251
DYNE-251 will be administered once every 4 weeks (Q4W) or once every 8 weeks (Q8W) over 24 weeks.
Drug: DYNE-251
Administered by IV infusion
Experimental: Placebo-Controlled MAD Period - Placebo
Placebo will be administered Q4W or Q8W over 24 weeks.
Drug: Placebo
Administered by IV infusion
Experimental: Open-Label and Long-Term Extension Period - DYNE-251
DYNE-251 will be administered Q4W or Q8W for up to 96 weeks after participants complete the Placebo-Controlled MAD Period of the study.
Drug: DYNE-251
Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25
Time Frame: Baseline, Week 25
Baseline, Week 25

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 145
Time Frame: Baseline, 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
Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 145
Time Frame: Baseline, up to Week 145
Baseline, up to Week 145
Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 145
Time Frame: Baseline, 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
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 145
Time Frame: Baseline, up to Week 145
Baseline, up to Week 145
Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Percentage of Participants With Antidrug Antibodies (ADAs)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 145
Time Frame: Baseline, up to Week 145
Baseline, up to Week 145
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
Time Frame: Baseline, Week 25
Baseline, Week 25
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
Time Frame: Baseline, Week 25
Baseline, Week 25
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
Time Frame: Baseline, up to Week 145
Baseline, up to Week 145
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
Time Frame: Baseline, Week 49
Baseline, Week 49
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
Time Frame: Baseline, Week 49
Baseline, Week 49
Change From Baseline in Muscle Tissue PDPF at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49
Time Frame: Baseline, Week 49
Baseline, Week 49
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
Time Frame: Baseline, up to Week 145
Baseline, up to Week 145
Change From Baseline in Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 145
Time Frame: Baseline, up to Week 145
Baseline, up to Week 145
Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC∞)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (λz)
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145
Total Body Clearance (CL) of DYNE-251
Time Frame: Through study completion, up to Week 145
Through study completion, up to Week 145

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dyne Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 12, 2022

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

August 30, 2022

First Submitted That Met QC Criteria

August 30, 2022

First Posted (Actual)

September 1, 2022

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DYNE251-DMD-201
  • 2021-005478-24 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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