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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05524883




Registration number
NCT05524883
Ethics application status
Date submitted
30/08/2022
Date registered
1/09/2022
Date last updated
7/05/2024

Titles & IDs
Public title
Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
Scientific 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
Secondary ID [1] 0 0
2021-005478-24
Secondary ID [2] 0 0
DYNE251-DMD-201
Universal Trial Number (UTN)
Trial acronym
DELIVER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Duchenne Muscular Dystrophy (DMD) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DYNE-251
Treatment: Drugs - Placebo

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.

Experimental: Placebo-Controlled MAD Period - Placebo - Placebo will be administered Q4W or Q8W over 24 weeks.

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.


Treatment: Drugs: DYNE-251
Administered by IV infusion

Treatment: Drugs: Placebo
Administered by IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Through study completion, up to Week 145
Primary outcome [2] 0 0
Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25
Timepoint [2] 0 0
Baseline, Week 25
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline, Week 25
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline, Week 25
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline, up to Week 145
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline, Week 49
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline, Week 49
Secondary outcome [6] 0 0
Change From Baseline in Muscle Tissue PDPF at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49
Timepoint [6] 0 0
Baseline, Week 49
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Baseline, up to Week 145
Secondary outcome [8] 0 0
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 145
Timepoint [8] 0 0
Baseline, up to Week 145
Secondary outcome [9] 0 0
Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 145
Timepoint [9] 0 0
Baseline, up to Week 145
Secondary outcome [10] 0 0
Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 145
Timepoint [10] 0 0
Baseline, up to Week 145
Secondary outcome [11] 0 0
Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 145
Timepoint [11] 0 0
Baseline, up to Week 145
Secondary outcome [12] 0 0
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 145
Timepoint [12] 0 0
Baseline, up to Week 145
Secondary outcome [13] 0 0
Change From Baseline in Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 145
Timepoint [13] 0 0
Baseline, up to Week 145
Secondary outcome [14] 0 0
Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax)
Timepoint [14] 0 0
Through study completion, up to Week 145
Secondary outcome [15] 0 0
Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax)
Timepoint [15] 0 0
Through study completion, up to Week 145
Secondary outcome [16] 0 0
Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast)
Timepoint [16] 0 0
Through study completion, up to Week 145
Secondary outcome [17] 0 0
Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC8)
Timepoint [17] 0 0
Through study completion, up to Week 145
Secondary outcome [18] 0 0
Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (?z)
Timepoint [18] 0 0
Through study completion, up to Week 145
Secondary outcome [19] 0 0
Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½)
Timepoint [19] 0 0
Through study completion, up to Week 145
Secondary outcome [20] 0 0
Total Body Clearance (CL) of DYNE-251
Timepoint [20] 0 0
Through study completion, up to Week 145
Secondary outcome [21] 0 0
Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz)
Timepoint [21] 0 0
Through study completion, up to Week 145
Secondary outcome [22] 0 0
Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss)
Timepoint [22] 0 0
Through study completion, up to Week 145
Secondary outcome [23] 0 0
Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue
Timepoint [23] 0 0
Through study completion, up to Week 145
Secondary outcome [24] 0 0
Percentage of Participants With Antidrug Antibodies (ADAs)
Timepoint [24] 0 0
Through study completion, up to Week 145

Eligibility
Key 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).
Minimum age
4 Years
Maximum age
16 Years
Sex
Males
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2026
Actual
Sample size
Target
88
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
02145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Belgium
State/province [12] 0 0
Liège
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Italy
State/province [14] 0 0
Lazio
Country [15] 0 0
Italy
State/province [15] 0 0
Liguria
Country [16] 0 0
Italy
State/province [16] 0 0
Lombardia
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Merseyside
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Northumberland
Country [20] 0 0
United Kingdom
State/province [20] 0 0
West Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Dyne Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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 period (96 weeks).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05524883
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dyne Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
+1-781-317-1919
Fax 0 0
Email 0 0
clinicaltrials@dyne-tx.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05524883