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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05481879




Registration number
NCT05481879
Ethics application status
Date submitted
28/07/2022
Date registered
1/08/2022

Titles & IDs
Public title
Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1
Scientific title
A Randomized, Placebo-Controlled, Multiple Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and Pharmacokinetics of DYNE-101 Administered to Participants With Myotonic Dystrophy Type 1
Secondary ID [1] 0 0
2023-510353-42-00
Secondary ID [2] 0 0
DYNE101-DM1-201
Universal Trial Number (UTN)
Trial acronym
ACHIEVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myotonic Dystrophy Type 1 (DM1) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DYNE-101
Treatment: Drugs - Placebo

Experimental: MAD Cohort: Placebo-Controlled Period: DYNE-101 - Participants will be randomized to receive ascending doses of DYNE-101, once every 4 weeks (Q4W) or once every 8 weeks (Q8W) for up to 24 weeks.

Placebo comparator: MAD Cohort: Placebo-Controlled Period: Placebo - Participants will be randomized to receive DYNE-101 matching placebo, Q4W or Q8W for up to 24 weeks.

Experimental: MAD Cohort: Treatment Period: DYNE-101 - Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q4W or Q8W for up to 24 weeks.

Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q4W or Q8W for up to 24 weeks.

Experimental: MAD Cohort: Long-Term Extension Period: DYNE-101 - Participants will receive DYNE-101, Q4W or Q8W for up to 144 weeks.

Experimental: Dose Expansion Cohort: Placebo-Controlled Period: DYNE-101 - Participants will receive DYNE-101, Q8W for up to 24 weeks.

Experimental: Dose Expansion Cohort: Placebo-Controlled Period: Placebo - Participants will receive DYNE-101 matching placebo, Q8W for up to 24 weeks.

Experimental: Dose Expansion Cohort: Treatment Period: DYNE-101 - Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q8W for up to 24 weeks.

Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q8W for up to 24 weeks.

Experimental: Dose Expansion Cohort: Long-Term Extension Period: DYNE-101 - Participants will receive DYNE-101, Q8W for up to 144 weeks.


Treatment: Drugs: DYNE-101
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
MAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Through study completion, up to Week 193
Primary outcome [2] 0 0
Dose Expansion Cohorts: Change From Baseline in Composite Alternative Splicing Index (CASI) in Skeletal Muscle Tissue up to Week 13
Timepoint [2] 0 0
Baseline up to Week 13
Secondary outcome [1] 0 0
MAD Cohorts: Change From Baseline in CASI in Skeletal Muscle Tissue
Timepoint [1] 0 0
Baseline up to Week 45
Secondary outcome [2] 0 0
MAD Cohorts: Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue
Timepoint [2] 0 0
Baseline up to Week 45
Secondary outcome [3] 0 0
MAD Cohorts: Change From Baseline in Hand Grip Relaxation Time
Timepoint [3] 0 0
Baseline up to Week 121
Secondary outcome [4] 0 0
MAD Cohorts: Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)
Timepoint [4] 0 0
Baseline up to Week 193
Secondary outcome [5] 0 0
MAD Cohorts: Change From Baseline in Quantitative Myometry Testing (QMT)
Timepoint [5] 0 0
Baseline up to Week 193
Secondary outcome [6] 0 0
MAD Cohorts: Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)
Timepoint [6] 0 0
Baseline up to Week 193
Secondary outcome [7] 0 0
MAD Cohorts: Change From Baseline in Stair-Ascend/Descend Test
Timepoint [7] 0 0
Baseline up to Week 121
Secondary outcome [8] 0 0
MAD Cohorts: Change From Baseline in 5 Times Sit to Stand (5×STS)
Timepoint [8] 0 0
Baseline up to Week 193
Secondary outcome [9] 0 0
MAD Cohorts: Change From Baseline in 9-Hole Peg Test (9-HPT)
Timepoint [9] 0 0
Baseline up to Week 193
Secondary outcome [10] 0 0
MAD Cohorts: Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101
Timepoint [10] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [11] 0 0
MAD Cohorts: Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101
Timepoint [11] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [12] 0 0
MAD Cohorts: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101
Timepoint [12] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [13] 0 0
MAD Cohorts: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC8) of DYNE-101 in Plasma
Timepoint [13] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [14] 0 0
MAD Cohorts: Apparent Terminal Elimination Rate Constant (?z) of DYNE-101 in Plasma
Timepoint [14] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [15] 0 0
MAD Cohorts: Apparent Terminal Elimination Half-Life (t1/2) of DYNE-101 in Plasma
Timepoint [15] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [16] 0 0
MAD Cohorts: Clearance (CL) of DYNE-101 in Plasma
Timepoint [16] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [17] 0 0
MAD Cohorts: Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma
Timepoint [17] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [18] 0 0
MAD Cohorts: Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma
Timepoint [18] 0 0
Pre-dose, and at multiple timepoints up to Week 193
Secondary outcome [19] 0 0
MAD Cohorts: Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue
Timepoint [19] 0 0
Up to Week 45
Secondary outcome [20] 0 0
MAD Cohorts: Number of Participants With Antidrug Antibodies (ADAs)
Timepoint [20] 0 0
Up to Week 193
Secondary outcome [21] 0 0
Dose Expansion Cohorts: Change From Baseline in Myotonia as Measured by vHOT up to Week 25
Timepoint [21] 0 0
Baseline up to Week 25
Secondary outcome [22] 0 0
Dose Expansion Cohorts: Change From Baseline in 10-MWRT up to Week 25
Timepoint [22] 0 0
Baseline up to Week 25
Secondary outcome [23] 0 0
Dose Expansion Cohorts: Change From Baseline in QMT up to Week 25
Timepoint [23] 0 0
Baseline up to Week 25
Secondary outcome [24] 0 0
Dose Expansion Cohorts: Change From Baseline in 5×STS up to Week 25
Timepoint [24] 0 0
Baseline up to Week 25
Secondary outcome [25] 0 0
Dose Expansion Cohorts: Change From Baseline in Myotonic Dystrophy Health Index (MDHI) Total Score up to Week 25
Timepoint [25] 0 0
Baseline up to Week 25

Eligibility
Key inclusion criteria
* Diagnosis of DM1 with trinucleotide repeat size >100.
* Age of onset of DM1 muscle symptoms =12 years.
* Clinically apparent myotonia equivalent to hand opening time of at least 2 seconds in the opinion of the Investigator.
* Hand grip strength and ankle dorsiflexion strength.
* Able to complete 10-MWRT, stair ascend/descend, and 5×STS at screening without the use of assistive devices such as canes, walkers, or orthoses.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of major surgical procedure within 12 weeks prior to the start of investigative product administration or an expectation of a major surgical procedure (eg, implantation of cardiac defibrillator) during the study.
* History of anaphylaxis.
* Medical condition other than DM1 that would significantly impact ambulation or participation in functional assessments.
* Treatment with medications that can improve myotonia within a period of 5 half-lives of the medication prior to performing screening assessments.
* Electrocardiogram (ECG) with the corrected QT interval by Fridericia's Formula (QTcF) =450 milliseconds (ms) in men and QTcF =460 ms in women, PR =240 ms, left bundle-branch block, or a conduction defect, which is clinically significant in the opinion of the Investigator.
* Percent predicted forced vital capacity (FVC) <50%.
* History of tibialis anterior biopsy within 3 months of Day 1 or planning to undergo tibialis anterior biopsies during study period for reasons unrelated to the study.
* Participant has a history of suicide attempt, suicidal behavior, or has any suicidal ideation within 6 months prior to Screening that meets criteria at a level of 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) or who, in the opinion of the Investigator, is at significant risk to commit suicide.
* Use of glucagon-like peptide 1 (GLP-1) agonist medications including semaglutide, dulaglutide, liraglutide, exenatide, or tirzepatide within a period of 5 half-lives of the medication prior to performing screening assessments.
* Significant weight loss during study participation may impact weight-based dosing, performance on muscle function assessments, and pharmacodynamic (PD) biomarkers.

Note: 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
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
5/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2029
Actual
Sample size
Target
104
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Paris
Country [2] 0 0
Germany
State/province [2] 0 0
Munich
Country [3] 0 0
Italy
State/province [3] 0 0
Milan
Country [4] 0 0
Italy
State/province [4] 0 0
Rome
Country [5] 0 0
Netherlands
State/province [5] 0 0
Nijmegen
Country [6] 0 0
New Zealand
State/province [6] 0 0
Auckland
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Newcastle-Upon-Tyne
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Salford

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05481879