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En undersøgelse til undersøgelse (BrAAVe)

18. september 2026 opdateret af: Sanofi

En fase 1/fase 2 open-label enkelt armstudie med dosisoptrapning (del A) og dosisudvidelse (del B) dele for at evaluere sikkerheden, tolerabiliteten og effektiviteten af ​​SAR446268, en adeno-associeret viral vektor-medieret genterapi i deltagere 10 til 50 år gammel med ikke-cornital myotonic dystrofy type 1 1

This is a Phase 1/Phase 2 open-label single arm, multicenter, and multinational study with SAR446268 for treatment of male and female participants 10 to 55 years old with non-congenital myotonic dystrophy (DM) type 1 (DM1).

The purpose of this study is to evaluate the safety and efficacy of SAR446268 in knocking down dystrophia myotonica protein kinase (DMPK) messenger ribonucleic acid (mRNA) levels and improving neuromuscular function in DM1 participants receiving a single intravenous (IV) administration of SAR446268. The study consists of a dose escalation part (Part A) during which single ascending doses of SAR446268 will be evaluated in 3 distinct cohorts and an optional fourth dose cohort. Once a safe and effective dose is identified, additional participants will be treated in Part B, the dose expansion phase of the study.

The study duration will be 112 weeks (approximately 2 years) for each participant in Parts A and B respectively and includes an optional pre-screening period, approximately 8-week screening phase and a 104-week follow-up period post-SAR446268 administration.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Each participant meeting the eligibility criteria for each of the study parts will receive a single dose administration of SAR446268.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

32

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

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

Studiekontakt

  • Navn: Trial Transparency email recommended (Toll free for US & Canada)
  • Telefonnummer: option 6 800-633-1610
  • E-mail: contact-us@sanofi.com

Studiesteder

  • Argentina
      • Buenos Aires, Argentina, 1181
        • Rekruttering
        • Hospital Italiano de Buenos Aires, Juan Domingo Peron 4190 - Site Number: 0320001
        • Kontakt:
        • Ledende efterforsker:
          • Ventura Simonovich
  • Australien
    • Queensland
      • Brisbane, Queensland, Australien, 4029
        • Rekruttering
        • Investigational Site Number : 0360001
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • Rekruttering
        • The Montreal Neurological Institute and Hospital, 3801 rue University - Site Number: 1240001
        • Kontakt:
        • Ledende efterforsker:
          • Dr. Erin O'Ferrall
  • Det Forenede Kongerige
      • Newcastle upon Tyne, Det Forenede Kongerige, NE7 7DN
        • Rekruttering
        • Investigational Site Number : 8260002
  • Forenede Stater
    • Florida
      • Gainesville, Florida, Forenede Stater, 32601
        • Rekruttering
        • University of Florida, 2004 Mowry Road - Site Number: 8400005
        • Kontakt:
        • Ledende efterforsker:
          • Dr. Subramony
      • Tampa, Florida, Forenede Stater, 33612
        • Rekruttering
        • University of South Florida - Neuromuscular Research, 13330 USF Laurel Drive - Site Number: 8400001
        • Ledende efterforsker:
          • Dr. Tuan Vu
        • Kontakt:
    • New York
      • New York, New York, Forenede Stater, 10032
        • Rekruttering
        • Columbia University Medical Center - Neurological Institute, 710 W. 168th, 2nd floor, suite 204 - Site Number : 8400003
        • Kontakt:
        • Ledende efterforsker:
          • Dr. Christina Ulane
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104
        • Rekruttering
        • Penn Medicine: University of Pennsylvania Health System- Site Number : 8400009
    • Virginia
      • Richmond, Virginia, Forenede Stater, 23298
        • Rekruttering
        • Virginia Commonwealth University Medical Center- Site Number : 8400006
  • Israel
      • Ramat Gan, Israel, 5262100
        • Rekruttering
        • Investigational Site Number : 3760002

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

10 år til 55 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

  • For Part A, participants must be 18 to 55 years of age inclusive, at the time of signing the informed consent.

  • For Part B, participants must be as follows:

    • 10 to 17 years of age inclusive, at the time of signing the informed consent or,
    • 18 to 55 years of age inclusive, at the time of signing the informed consent.

  • Participants with non-congenital onset DM1

  • Participants presenting with signs of DM1 including myotonia and muscle weakness, as diagnosed previously by a clinician based on medical history.

  • Participants with genetic diagnosis of DM1 [cytosine-thymine-guanine (CTG) repeat length ≥50 in one allele from medical history]

  • Participants who can walk independently for at least 10 meters at screening (orthoses and ankle braces allowed).

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  • Participants with neutralizing antibodies against the AAV.SAN011 capsid

  • Participants with left ventricular ejection fraction <50%

  • Participants with liver or biliary disease defined as having at least one of the following:

    • ALT >3 x ULN and AST >3 x ULN
    • Alkaline phosphatase >3 x ULN
    • Total bilirubin >1.5 x ULN (unless has a genetically confirmed diagnosis of Gilbert's syndrome)
    • Direct bilirubin ≥1.5 x ULN
    • Participants with International normalized ratio >1.5

  • Participants with renal disease defined as:

    • Serum creatinine >1.5 x ULN and/or estimated glomerular filtration rate <60 mL/min/1.73 m2 as determined by Chronic Kidney Disease Epidemiology Collaboration (2021) for those age ≥18 years and Bedside Schwartz Equation for those <18 years

  • Participants with chronic respiratory insufficiency and on long term/hull-time ventilatory assistance requiring at least 6 hours per day for at least 21 consecutive days.

  • Participants with contraindication to corticosteroid or with conditions that could worsen in the presence of corticosteroids, as determined by the Investigator.

  • Participants with active hepatitis B or C infection; HBsAg (+), or HCV RNA (+), or current antiviral therapy for either.

  • Participants with HBcAb (+) who are not amenable for prophylactic anti-HBV therapy or pre-emptive therapy guided by serial HBV DNA monitoring during the corticosteroids therapy.

  • Participants at high risk for tuberculosis reactivation during the corticosteroids therapy as determined by the Investigator.

  • Participants with a known HIV infection

  • Participants with serious intercurrent illness that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival.

  • Participants with recent history of or current drug or alcohol abuse in the past 12 months prior to screening.

  • Participants with history of tibialis anterior biopsy within 12 weeks from Day 1 or planning to undergo tibialis anterior biopsies during the duration of this clinical trial.

  • Participants with significant developmental delay, intellectual disability, or behavioral neuropsychiatric manifestations as determined by the Investigator.

  • Participants with previous systemic corticosteroids treatment at doses of >5 mg/day within 15 days of Day 1

  • Participants with previous treatment with anti-myotonic medication within 15 days of Day 1

  • Participants not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

  • Participants who have been classified as severe cardiac risk by the Investigator.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

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: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: SAR446268

Participants will receive a single dose of SAR446268 on Day 1
Biologisk: SAR446268

Pharmaceutical form: Solution for infusion; Route of administration: IV infusion

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Del B: Andel af deltagere med mindst 40% DMPK mRNA -knockdown i muskelbiopsi i uge 12 og 52 efter SAR446268 -administration
Tidsramme: Uger 12 og 52
Uger 12 og 52
Part A and Part B: Incidence of treatment-emergent adverse events (TEAEs) following SAR446268 administration
Tidsramme: Baseline to Week 52

Number of TEAEs post-SAR446268 administration
Baseline to Week 52

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Del A: Andel af deltagere med mindst 40% DMPK mRNA -knockdown i muskelbiopsi i uge 12 og 52 efter SAR446268 -administration
Tidsramme: Uger 12 og 52
Uger 12 og 52
Del A: Ændring i DMPK mRNA -niveauer i muskelbiopsi fra baseline til uge 12 og 52 efter SAR446268 -administration
Tidsramme: Baseline til uge 12 og 52
Baseline til uge 12 og 52
Del A: Ændring i RNA -splejsningsindeks i muskelbiopsi fra baseline til uge 12 og 52 efter SAR446268 -administration
Tidsramme: Baseline til uge 12 og 52
Baseline til uge 12 og 52
Del A: Vurdering af varigheden af ​​AAV-vektorudgydelse af SAR446268 ved prøveudtagning af urin, spyt og sæd med 4-ugers intervaller efter SAR446268-administration
Tidsramme: Baseline, uger 4, 8 og 12
Baseline, uger 4, 8 og 12
Del B: Ændring i DMPK mRNA -knockdown i muskelbiopsi fra baseline til uge 12 og 52 efter SAR446268 -administration
Tidsramme: Baseline til uge 12 og 52
Baseline til uge 12 og 52
Del B: Ændring i RNA -splejsningsindeks i muskelbiopsi fra baseline til uge 12 og 52 efter SAR446268 -administration
Tidsramme: Baseline til uge 12 og 52
Baseline til uge 12 og 52
Del B: Vurdering af varigheden af ​​AAV-udgydelse af SAR446268 ved prøveudtagning af urin, spyt og sæd med 4-ugers intervaller efter SAR446268-administration
Tidsramme: Baseline, uger 4, 8 og 12
Baseline, uger 4, 8 og 12
Part A: Change in 10-meter walk-run test from baseline to Weeks 26 and 52 following SAR446268 administration
Tidsramme: Baseline to Week 26 and 52

The 10-meter walk-run test is a mobility test that measures how fast a participant can traverse 10 meters with or without assisted devices.
Baseline to Week 26 and 52
Part A: Change in myotonia from baseline to Weeks 26 and 52 following SAR446268 administration as measured by the hand opening time (middle finger)
Tidsramme: Baseline to Week 26 and 52

This test for myotonia measures how quickly a participant can open his/her hand after making a tight fist.
Baseline to Week 26 and 52
Part A: Change in bilateral hand grip test from baseline to Weeks 26 and 52 following SAR446268 administration
Tidsramme: Baseline to Week 26 and 52

This test for strength of the hand muscles measures the maximum force generated by a participant's hand grip using a dynamometer.
Baseline to Week 26 and 52
Part B: Change in 10-meter walk-run test from baseline to Weeks 26 and 52 following SAR446268 administration
Tidsramme: Baseline to Week 26 and 52

The 10-meter walk-run test is a mobility test that measures how fast a participant can traverse 10 meters with or without assisted devices.
Baseline to Week 26 and 52
Part B: Change in myotonia from baseline to Weeks 26 and 52 following SAR446268 administration as measured by the hand opening time (middle finger)
Tidsramme: Baseline to Week 26 and 52

This test for myotonia measures how quickly a participant can open his/her hand after making a tight fist.
Baseline to Week 26 and 52
Part B: Change in bilateral hand grip test from baseline to Weeks 26 and 52 following SAR446268 administration
Tidsramme: Baseline to Week 26 and 52

This test for strength of the hand muscles measures the maximum force generated by a participant's hand grip using a dynamometer.
Baseline to Week 26 and 52

Samarbejdspartnere og efterforskere

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

Sponsor

Sanofi

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

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)

23. juli 2025

Primær færdiggørelse (Anslået)

28. februar 2029

Studieafslutning (Anslået)

27. april 2032

Datoer for studieregistrering

Først indsendt

19. februar 2025

Først indsendt, der opfyldte QC-kriterier

19. februar 2025

Først opslået (Faktiske)

25. februar 2025

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

21. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

18. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • DFI17808
  • U1111-1290-9594 (Registry Identifier: ICTRP)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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