A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Adeno-associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Patients With Late-onset OTC Deficiency

Activo, no reclutaFase 3ClinicalTrials.gov

ID: NCT05345171Tipo: INTERVENTIONALInicio: 18 de oct de 2022Fin estimado: 1 de mar de 2031

Traducción no disponible, mostrando original

Resumen

The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine transcarbamylase (OTC) function by maintaining safe plasma ammonia levels.

Descripción detallada

This study is a Phase 3, randomized, double-blind, placebo-controlled study of DTX301 in patients with late-onset OTC deficiency 12 years of age and older. Participants will be randomized 1:1 to DTX301 or placebo and followed closely for 36-64 weeks. Between Week 36 and Week 64, eligible participants will cross over and receive DTX301 if they had previously received placebo, and some who received DTX301 may receive placebo. The planned study duration is up to 324 weeks. Upon completion of this study or early withdrawal, all participants who received DTX301 are invited to enroll in the Disease Monitoring Program (DMP) for follow-up for up to an additional 5 years.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

Confirmed clinical diagnosis of late-onset OTC deficiency with historical documentation by enzymatic (ie, liver biopsy), biochemical (ie, hyperammonemia in the presence of elevated plasma glutamine, low citrulline, and elevated spot urine orotic acid), or molecular testing (ie, OTC analysis)
Free from symptomatic hyperammonemia and has not required emergent active intervention for hyperammonemia within 4 weeks before screening/baseline
If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for ≥ 4 weeks prior to screening
If on a protein-restricted diet, must be on a stable total daily protein intake that does not vary more than 20% for ≥ 4 weeks prior to screening
From the time written informed consent through Visit 28, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant. If male, agree not father a child or donate sperm

Criterios de exclusión

Significant hepatic inflammation or cirrhosis
Estimated glomerular filtration rate \< 60 mL/min/1.73 m2 at screening by the 2021 CKD-EPI creatinine-based formula (Inker et al., 2021) for patients ≥ 18 years of age or the Schwartz bedside formula (Schwartz and Work, 2009) for patients \< 18 years of age
Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, documented by current use of antiviral therapy for HBV or HCV or by hepatitis B surface antigen (HBsAg) or HCV RNA positivity
Active infection (viral or bacterial)
Detectable pre-existing antibodies to the AAV8 capsid
Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results
Participation (current or previous) in another gene transfer study

Intervenciones

genetic

DTX301

non-replicating, self-complementary recombinant adeno-associated virus serotype 8 (AAV8) vector

other

Placebo

normal saline infusion

drug

Oral Corticosteroids

Participants who receive DTX301 solution will receive oral corticosteroids.

drug

Placebo for oral corticosteroids

Participants who receive Placebo will receive placebo corticosteroids to maintain the study blind

drug

Sodium Acetate

A tracer for the Ureagenesis Rate Test (URT)

Ubicaciones

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

Clinica Universitaria Reina Fabiola

Córdoba, Argentina

Patrocinadores

PrincipalUltragenyx Pharmaceutical Inc

Aviso: La información de este ensayo proviene de fuentes públicas y tiene carácter exclusivamente informativo. No constituye asesoramiento médico, regulatorio ni de ningún otro tipo. Las traducciones son automatizadas y no poseen validez oficial. Consultá siempre con un profesional de la salud. Ver Términos de Uso.

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