Resumen

Este es un estudio fase 1/fase 2, abierto, de un solo brazo, multicéntrico y multinacional con SAR446268 para el tratamiento de participantes masculinos y femeninos de 10 a 50 años con distrofia miotónica (DM) tipo 1 de inicio no congénito (DM1). El objetivo de este estudio es evaluar la seguridad y eficacia de SAR446268 para reducir los niveles del ARN mensajero (ARNm) de la proteína quinasa de la distrofia miotónica (DMPK) y mejorar la función neuromuscular en participantes con DM1 que reciben una única administración intravenosa (IV) de SAR446268. El estudio consta de una parte de escalada de dosis (Parte A), durante la cual se evaluarán dosis únicas ascendentes de SAR446268 en 3 cohortes diferenciadas y una 4.ª cohorte de dosis opcional. Una vez identificada una dosis segura y eficaz, se tratará a participantes adicionales en la Parte B, la fase de expansión de dosis del estudio. La duración del estudio será de 110 semanas (aproximadamente 2 años) para cada participante en las Partes A y B respectivamente, e incluye una fase de selección de 6 semanas y un período de seguimiento de 104 semanas tras la administración de SAR446268.

Descripción detallada

Cada participante que cumpla los criterios de elegibilidad de cada una de las partes del estudio recibirá una única administración de SAR446268.

Elegibilidad

Edad mínima: 10 YearsEdad máxima: 50 YearsSexo: ALL

Criterios de inclusión

For Part A, participants must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
For Part B, participants must be as follows:
to 17 years of age inclusive, at the time of signing the informed consent or,
to 50 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).
Participants who have been classified according to cardiac risk by the Investigator as:
Moderate risk participants with pacemaker and/or implantable cardioverter-defibrillator (ICD) for Part A
Low, moderate, or high cardiac risk for Part B

Criterios de exclusión

Participants with neutralizing antibodies against the AAV.SAN011 capsid
Participants with left ventricular ejection fraction (LVEF) \<50%
Participants with liver or biliary disease defined as having at least one of the following:
Alanine aminotransferase (ALT) \>2 x ULN and aspartate aminotransferase (AST) \>2 x ULN
Alkaline phosphatase \>2 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 (CKD-EPI) (2021) for those age ≥18 years and Bedside Schwartz Equation for those \<18 years
Participants with chronic respiratory insufficiency and on non-invasive ventilatory support, nighttime ventilatory support or full-time ventilation.
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.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

SAR446268

Ubicaciones

Hospital Italiano de Buenos Aires, Juan Domingo Peron 4190 - Site Number: 0320001

Patrocinadores

Contactos

Trial Transparency email recommended (Toll free for US & Canada)