Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

Sikkerhed, tolerabilitet, farmakodynamisk, effektivitet og farmakokinetisk undersøgelse af DYNE-101 hos deltagere med myotonisk dystrofi type 1 (ACHIEVE)

19. september 2026 opdateret af: Dyne Therapeutics

Et randomiseret, placebo-kontrolleret, multiple stigende dosisstudie, der vurderer sikkerhed, tolerabilitet, farmakodynamik, effektivitet og farmakokinetik af DYNE-101 administreret til deltagere med myotonisk dystrofi type 1

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 (208 weeks) in both multiple-ascending dose (MAD) and dose expansion cohorts.

Studieoversigt

Status

Aktiv, ikke rekrutterende

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

127

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Australien
    • Victoria
      • Fitzroy, Victoria, Australien, 3065
        • St. Vincent's Hospital
  • Det Forenede Kongerige
      • London, Det Forenede Kongerige, NW1 2BU
        • University College London Hospitals
      • Newcastle upon Tyne, Det Forenede Kongerige
        • John Walton Muscular Dystrophy Research Centre
      • Salford, Det Forenede Kongerige, M6 8HD
        • Salford Royal Hospital
  • Forenede Stater
    • California
      • Stanford, California, Forenede Stater, 94305
        • Stanford University
    • Florida
      • Gainesville, Florida, Forenede Stater, 32610
        • University of Florida College of Medicine
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202
        • Indiana University School of Medicine
    • Iowa
      • Iowa City, Iowa, Forenede Stater, 52242
        • University of Iowa
    • Missouri
      • St Louis, Missouri, Forenede Stater, 63110
        • Washington University in St. Louis
    • New York
      • Rochester, New York, Forenede Stater, 14642
        • University of Rochester Medical Center
    • Texas
      • Denton, Texas, Forenede Stater, 76208
        • Neurology Rare Disease Center
    • Virginia
      • Richmond, Virginia, Forenede Stater, 23298
        • Virginia Commonwealth University (VCU)
  • Frankrig
      • Nantes, Frankrig, 44093
        • CHU de Nantes
      • Paris, Frankrig, 75013
        • Institut de Myologie
  • Holland
      • Nijmegen, Holland
        • Radboud Medical Center
  • Italien
      • Milan, Italien, 20162
        • Centro Clinico Nemo
      • Rome, Italien, 00168
        • Fondazione Policlinico Universitario A Gemelli-Rome
  • New Zealand
      • Auckland, New Zealand, 1023
        • NZCR Auckland
  • Tyskland
      • Berlin, Tyskland, 10117
        • Charité - Universitätsmedizin Berlin
      • Munich, Tyskland, 80336
        • Ludwig Maximilians University, Munich - Friedrich Baur Institut

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 65 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: DYNE-101

Administered by IV infusion
Placebo komparator: MAD Cohort: Placebo-Controlled Period: Placebo

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

Administered by IV infusion
Eksperimentel: 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.
Medicin: DYNE-101

Administered by IV infusion

Medicin: Placebo

Administered by IV infusion
Eksperimentel: MAD Cohort: Long-Term Extension Period: DYNE-101

Participants will receive DYNE-101, Q4W or Q8W for up to 208 weeks.
Medicin: DYNE-101

Administered by IV infusion
Eksperimentel: Dose Expansion Cohort: Placebo-Controlled Period: DYNE-101

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

Administered by IV infusion
Eksperimentel: Dose Expansion Cohort: Placebo-Controlled Period: Placebo

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

Administered by IV infusion
Eksperimentel: 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.
Medicin: DYNE-101

Administered by IV infusion

Medicin: Placebo

Administered by IV infusion
Eksperimentel: Dose Expansion Cohort: Long-Term Extension Period: DYNE-101

Participants will receive DYNE-101, Q8W for up to 208 weeks.
Medicin: DYNE-101

Administered by IV infusion

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Dosisekspansionskohorter: Skift fra baseline i myotonia målt ved åbningstid for videovirksomhed (VHOT)
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
MAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Tidsramme: Through study completion, up to Week 257
Through study completion, up to Week 257

Sekundære resultatmål

Resultatmål
Tidsramme
MAD -kohorter: Skift fra baseline i dystrofi myotonica proteinkinase (DMPK) ribonukleinsyre (RNA) ekspression i muskelvæv
Tidsramme: Baseline op til uge 45
Baseline op til uge 45
MAD -kohorter: Skift fra baseline i håndgrebets afslapningstid
Tidsramme: Baseline op til uge 121
Baseline op til uge 121
MAD-kohorter: Skift fra baseline i trappesag/nedgangstest
Tidsramme: Baseline op til uge 121
Baseline op til uge 121
MAD-kohorter: Antisense oligonukleotid (ASO) koncentration af DYNE-101 i muskelvæv
Tidsramme: Op til uge 45
Op til uge 45
MAD -kohorter: Skift fra baseline i sammensat alternativt splejsningsindeks (CASI) i skeletmuskelvæv
Tidsramme: Baseline op til uge 45
Baseline op til uge 45
Dosisudvidelseskohorter: Skift fra baseline i CASI i skeletmuskelvæv
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline i QMT i alt
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline i 10-MWRT
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline i 5 × STS
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline i 9-HPT
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisekspansionskohorter: Skift fra baseline i myotonisk dystrofi Sundhedsindeks (MDHI) Total score
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisekspansionskohorter: Patient Globalt indtryk af forandring (PGI-C)
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Kliniker Global Impression of Change (CGI-C)
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisekspansionskohorter: Skift fra baseline i patientens globale indtryk af sværhedsgrad (PGI-S)
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline i klinikeren Globalt indtryk af sværhedsgrad (CGI-S)
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline i MDHI -underskala -scoringer
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline ved i myotonisk dystrofi Type 1 Aktivitet og deltagelsesskala (DM1-Activ^C) Total score
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
Dosisudvidelseskohorter: Skift fra baseline i procent forudsagt håndgrebstyrke
Tidsramme: Baseline op til uge 25
Baseline op til uge 25
MAD Cohorts: Change From Baseline in Myotonia as Measured by vHOT
Tidsramme: Baseline up to Week 257
Baseline up to Week 257
MAD Cohorts: Change From Baseline in Quantitative Myometry Testing (QMT)
Tidsramme: Baseline up to Week 257
Baseline up to Week 257
MAD Cohorts: Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)
Tidsramme: Baseline up to Week 257
Baseline up to Week 257
MAD Cohorts: Change From Baseline in 5 Times Sit to Stand (5×STS)
Tidsramme: Baseline up to Week 257
Baseline up to Week 257
MAD Cohorts: Change From Baseline in 9-Hole Peg Test (9-HPT)
Tidsramme: Baseline up to Week 257
Baseline up to Week 257
MAD Cohorts: Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Apparent Terminal Elimination Half-Life (t1/2) of DYNE-101 in Plasma
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Clearance (CL) of DYNE-101 in Plasma
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma
Tidsramme: Pre-dose, and at multiple timepoints up to Week 257
Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Number of Participants With Antidrug Antibodies (ADAs)
Tidsramme: Up to Week 257
Up to Week 257

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Dyne Therapeutics

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

5. september 2022

Primær færdiggørelse (Anslået)

1. juli 2029

Studieafslutning (Anslået)

1. juli 2029

Datoer for studieregistrering

Først indsendt

28. juli 2022

Først indsendt, der opfyldte QC-kriterier

28. juli 2022

Først opslået (Faktiske)

1. august 2022

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

23. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

19. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • DYNE101-DM1-201
  • 2023-510353-42-00 (Ctis)
  • 2023 (U.S. NIH-bevilling/kontrakt)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ja

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Abonner