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

Primary Purpose

Myotonic Dystrophy Type 1 (DM1)

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

DYNE-101

Placebo

About this trial

This is an interventional treatment trial for Myotonic Dystrophy Type 1 (DM1)

Eligibility Criteria

18 Years - 49 Years (Adult)All SexesDoes not accept 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 averaged from both sides ≥20th and ≤80th percentile for age, sex, and height at screening.
Able to complete 10MWT, stair ascend/descend, 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 QTc ≥460 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.

Note: Other inclusion and exclusion criteria may apply.

Sites / Locations

Institut de MyologieRecruiting
Ludwig Maximilians University, Munich - Friedrich Baur InstitutRecruiting
Centro Clinico NemoRecruiting
Radboud Medical CenterRecruiting
University of Auckland Research CentreRecruiting
University College London HospitalsRecruiting
John Walton Muscular Dystrophy Research CentreRecruiting
Salford Royal HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Placebo-Controlled MAD Period: DYNE-101

Placebo-Controlled MAD Period: Placebo

Treatment Period: DYNE-101

Long-Term Extension Period: DYNE-101

Arm 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.

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

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.

Participants will receive DYNE-101, Q4W or Q8W for up to 96 weeks.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Secondary Outcome Measures

Change From Baseline in Splicing Index in Skeletal Muscle Tissue

Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue

Change From Baseline in Hand Grip Relaxation Time

Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)

Change From Baseline in Quantitative Myometry Testing (QMT)

Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)

Change From Baseline in Stair-Ascend/Descend Test

Change From Baseline in 5 Times Sit to Stand (5×STS)

Change From Baseline in 9-Hole Peg Test (9-HPT)

Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101

Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101

Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101

Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma

Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma

Apparent Terminal Elimination Half-Life (t½) of DYNE-101 in Plasma

Clearance (CL) of DYNE-101 in Plasma

Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma

Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma

Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue

Percentage of Participants With Antidrug Antibodies (ADAs)

Full Information

NCT ID

NCT05481879

First Posted

July 28, 2022

Last Updated

May 31, 2023

Sponsor

Dyne Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT05481879

Brief Title

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

Acronym

ACHIEVE

Official 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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 5, 2022 (Actual)

Primary Completion Date

July 2026 (Anticipated)

Study Completion Date

July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Dyne Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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 multiple-ascending dose (MAD) Placebo-Controlled Period (24 weeks), a Treatment Period (24 weeks) and a Long-Term Extension (LTE) Period (96 weeks).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myotonic Dystrophy Type 1 (DM1)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo-Controlled MAD Period: DYNE-101

Arm Type

Experimental

Arm 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.

Arm Title

Placebo-Controlled MAD Period: Placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Treatment Period: DYNE-101

Arm Type

Experimental

Arm Description

Arm Title

Long-Term Extension Period: DYNE-101

Arm Type

Experimental

Arm Description

Participants will receive DYNE-101, Q4W or Q8W for up to 96 weeks.

Intervention Type

Drug

Intervention Name(s)

DYNE-101

Intervention Description

Administered by IV infusion

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered by IV infusion

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Time Frame

Through study completion, up to Week 145

Secondary Outcome Measure Information:

Title

Change From Baseline in Splicing Index in Skeletal Muscle Tissue

Time Frame

Baseline up to Week 97

Title

Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue

Time Frame

Baseline up to Week 97

Title

Change From Baseline in Hand Grip Relaxation Time

Time Frame

Baseline up to Week 145

Title

Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)

Time Frame

Baseline up to Week 145

Title

Change From Baseline in Quantitative Myometry Testing (QMT)

Time Frame

Baseline up to Week 145

Title

Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)

Time Frame

Baseline up to Week 145

Title

Change From Baseline in Stair-Ascend/Descend Test

Time Frame

Baseline up to Week 145

Title

Change From Baseline in 5 Times Sit to Stand (5×STS)

Time Frame

Baseline up to Week 145

Title

Change From Baseline in 9-Hole Peg Test (9-HPT)

Time Frame

Baseline up to Week 145

Title

Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Apparent Terminal Elimination Half-Life (t½) of DYNE-101 in Plasma

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Clearance (CL) of DYNE-101 in Plasma

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma

Time Frame

Pre-dose, and at multiple timepoints up to Week 145

Title

Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue

Time Frame

Up to Week 97

Title

Percentage of Participants With Antidrug Antibodies (ADAs)

Time Frame

Up to Week 145

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

49 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. 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. Note: Other inclusion and exclusion criteria may apply.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dyne Clinical Trials

Phone

+1-781-317-1919

clinicaltrials@dyne-tx.com

Facility Information:

Facility Name

Institut de Myologie

City

Paris

ZIP/Postal Code

75013

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr. Guillaume Bassez

Phone

+33142163791

g.bassez@institut-myologie.org

Facility Name

Ludwig Maximilians University, Munich - Friedrich Baur Institut

City

Munich

ZIP/Postal Code

80336

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marko Mijic

Phone

+49 89 440057078

Marko.Mijic@med.uni-muenchen.de

First Name & Middle Initial & Last Name & Degree

Benedikt Schoser, MD

Facility Name

Centro Clinico Nemo

City

Milan

ZIP/Postal Code

20162

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alessandra DiBari

Phone

+393386936070

alessandra.dibari@centrocliniconemo.it

First Name & Middle Initial & Last Name & Degree

Valeria Sansone, MD, PhD

Facility Name

Radboud Medical Center

City

Nijmegen

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joost Kools, MD

joost.kools@radboudumc.nl

Facility Name

University of Auckland Research Centre

City

Auckland

ZIP/Postal Code

1023

Country

New Zealand

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Miriam Rodrigues

Phone

+6408007883437

miriam.rodrigues@auckland.ac.nz

Facility Name

University College London Hospitals

City

London

ZIP/Postal Code

NW1 2BU

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr. Chris Turner

Phone

+44 020 3448 8005

jreveira@nhs.net

Facility Name

John Walton Muscular Dystrophy Research Centre

City

Newcastle-Upon-Tyne

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jordi Diaz-Manera, MD, PhD

nmd.clinicaltrials@newcastle.ac.uk

Facility Name

Salford Royal Hospital

City

Salford

ZIP/Postal Code

M6 8HD

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kathryn Slevin

Phone

+44 0161 206 5203

neuroresearch.nurse@nca.nhs.uk

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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