Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1 (ACHIEVE)

Dyne Therapeutics

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Myotonic Dystrophy Type 1 (DM1)

Treatments

Drug: Placebo

Drug: DYNE-101

Study type

Interventional

Funder types

Industry

Identifiers

NCT05481879

2023-510353-42-00 (EU Trial (CTIS) Number)

DYNE101-DM1-201

Details and patient eligibility

About

The primary purpose of the study is to evaluate the safety and tolerability of multiple intravenous (IV) doses of DYNE-101 administered to participants with Myotonic Dystrophy Type 1 (DM1).

The study consists of 4 periods: A Screening Period (up to 8 weeks), a Placebo-Controlled Period (24 weeks), a Treatment Period (24 weeks) and a Long-Term Extension (LTE) Period (168 weeks) in both multiple-ascending dose (MAD) and dose expansion cohorts.

Enrollment

116 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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 (MAD cohorts only), and 5×STS at screening without the use of assistive devices such as canes, walkers, or orthoses.

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Quadruple Blind

116 participants in 8 patient groups, including a placebo group

MAD Cohort: Placebo-Controlled Period: DYNE-101

Experimental group

Description:

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.

Treatment:

Drug: DYNE-101

MAD Cohort: Placebo-Controlled Period: Placebo

Placebo Comparator group

Description:

Participants will be randomized to receive DYNE-101 matching placebo, Q4W or Q8W for up to 24 weeks.

Treatment:

Drug: Placebo

MAD Cohort: Treatment Period: DYNE-101

Experimental group

Description:

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.

Treatment:

Drug: DYNE-101

Drug: Placebo

MAD Cohort: Long-Term Extension Period: DYNE-101

Experimental group

Description:

Participants will receive DYNE-101, Q4W or Q8W for up to 168 weeks.

Treatment:

Drug: DYNE-101

Dose Expansion Cohort: Placebo-Controlled Period: DYNE-101

Experimental group

Description:

Participants will receive DYNE-101, Q8W for up to 24 weeks.

Treatment:

Drug: DYNE-101

Dose Expansion Cohort: Placebo-Controlled Period: Placebo

Experimental group

Description:

Participants will receive DYNE-101 matching placebo, Q8W for up to 24 weeks.

Treatment:

Drug: Placebo

Dose Expansion Cohort: Treatment Period: DYNE-101

Experimental group

Description:

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.

Treatment:

Drug: DYNE-101

Drug: Placebo

Dose Expansion Cohort: Long-Term Extension Period: DYNE-101

Experimental group

Description:

Participants will receive DYNE-101, Q8W for up to 168 weeks.

Treatment:

Drug: DYNE-101