Activo, sin reclutamientoNCT04174105Registro de ClinicalTrials.gov

Gene Transfer Study in Patients With Late Onset Pompe Disease

Pompe Disease (Late-onset)

Pregúntale a WCR sobre este estudio Registro oficial ↗

LO ESENCIAL

De qué trata este estudio

El registro no identifica actualmente este estudio como reclutando. Consulta su estado antes de planificar una evaluación.

Tipo de estudio: De intervención
Fase: Fase 1 / Fase 2
Rango de edad: 18 años - 80 años
Sexo admitido: Todos los sexos
Voluntarios sanos: No aceptados
Participantes: 11 Real

Estos son puntos de partida, no una decisión de elegibilidad. El equipo debe revisar todos los requisitos.

Las explicaciones y la navegación están en español. Los textos proporcionados por el registro, incluidos títulos, resúmenes y criterios, se conservan en su idioma original. Puedes pedir orientación en español a WCR.

Acerca de la investigación

This is a phase 1/2 open-label, ascending dose, multicenter clinical study to evaluate the safety and efficacy of AT845 in adult (aged ≥ 18 years) subjects, ambulatory or nonambulatory, with Late Onset Pompe Disease (LOPD).

Leer la descripción completa

This study (FORTIS) will evaluate the safety and efficacy of an investigational gene replacement therapy, AT845, in adult subjects with LOPD. Subjects will receive a single dose of AT845 delivered via intravenous (IV) infusion.

Up to 3 nominal dose levels of AT845 are planned to be evaluated in this study. A single AT845 administration via IV infusion is planned for each subject. The initial dosing cohort received a single dose of 3x10\^13 vg/kg of AT845. The second dose cohort will receive a single dose of 6×10\^13 vg/kg. The third dose cohort will receive a single dose of 1×10\^14 vg/kg. Dose escalation between cohorts will be based on evaluations of safety and in consultation with the independent DMC.

There will be a core observation period of 48 weeks with scheduled visits and assessments. Following the conclusion of the core observation period, subjects will be seen every 6 months for a safety follow-up visit for up to 10 years postdose.

¿Quién podría participar?

La lista siguiente contiene el texto del patrocinador. Puede incluir condiciones, tratamientos previos, resultados de pruebas y otros requisitos. Aparecer en tu búsqueda no significa que califiques.

Inclusion Criteria:

Participant is aged ≥ 18 years.
Participant has a documented clinical diagnosis of Pompe disease by genetic testing.
Participant has received enzyme replacement therapy (ERT) with rhGAA for the previous ≥ 2 years.
Participant has been on a stable standard dose (at least 20 mg/kg every 2 weeks) of ERT with rhGAA for at least the previous 6 months.
Participant or legally authorized representative(s) (LAR) (if applicable) provides written informed consent.
Participant and LAR(s) are willing and able to comply with study visits and study procedures.
Participant must agree to refrain from blood or blood products donation and sperm or egg donation from the time of AT845 administration until the later of 90 days or 3 consecutive negative viral shedding samples
Participants enrolled in previous protocol versions 1 through 9: Participant has upright FVC ≥ 30% of predicted normal value. Participants enrolled starting with protocol version 10 and subsequent amendments: Participant has upright FVC ≥ 30% and ≤ 85% of predicted normal value.
Participants enrolled starting with protocol version 10 and subsequent amendments: Participant who is able to ambulate ≥ 40 m without stopping and without the use of an assistive device. The use of an assistive device for community ambulation is acceptable. (Participants enrolled under previous protocol versions 1 through 9 will not be excluded if they do not meet this criterion during Rescreening visit).

Exclusion Criteria:

Participant is currently participating in an interventional study or has received gene or cell therapy.
Participant tests positive for AAV8 antibodies with titers \>1:20 neutralizing.
Participant has received immune-modulating agents within 90 days before dosing (use of inhaled corticosteroids is allowed); use of other concomitant medications to manage chronic conditions must have been stable for at least 30 days before dosing. Concomitant medications that may predispose the participant to peripheral neuropathy will be evaluated.
Participant has any clinically significant laboratory values (other than those directly associated with LOPD \[e.g., GAA, serum creatine kinase (CK)\]) that would preclude participation in the study.
Participant has serological or viral load evidence of HIV-1 or HIV-2.
Participant has received drugs for treatment of myopathy or neuropathy with immunosuppressive therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin, rituximab) within 3 months prior to starting the study
Participant has a high risk for a severe allergic reaction to rhGAA (ie, previous moderate to severe anaphylactic reaction to alglucosidase alfa or and/or a history of sustained high immunoglobulin G \[IgG\] antibody titers to alglucosidase alfa that suggests a high risk for an allergic reaction to ERT).
Participant has a history of hypersensitivity to β2 agonist drugs such as albuterol, levalbuterol, bitolterol, pirbuterol, terbutaline, salmeterol, which contraindicates pulmonary function testing.
Participant has an active viral infection based on clinical observation.
Participant has a history of or concurrent medical condition other than Pompe disease that could jeopardize safety of the participant or impact study results.
Participant has a history of, or currently has, a clinically important cardiac condition, such as an echocardiogram (ECHO) with ejection fraction below 40% or has symptoms or signs of cardiomyopathy that precludes enrollment.
Participant has a contraindication to study drug or to corticosteroids, or has demonstrated hypersensitivity to any of the components of the study drug.
Participant tests positive for GAA antibodies with titers \> 1:50,000 total
Participant has a history of hypersensitivity to MRI contrast agents including gadolinium.
Participant has a known hypersensitivity to local anesthetics such as lidocaine.
Participant has a bleeding diathesis, e.g., due to anti-coagulation or anti-platelet treatments.
Participant has a concurrent medical condition (including uncontrolled diabetes, alcohol use disorder, certain autoimmune conditions, Lyme disease, active malignancy requiring chemotherapy and/or radiation, uremic nephropathy, known exposure to heavy metals) commonly associated with peripheral neuropathy. Other concurrent medical conditions that may predispose to peripheral neuropathy will be evaluated and action taken on a case-by-case basis, following discussion between the Investigator and Medical Monitor.
Participant who is unwilling to withdraw from ERT.
Participant has an active symptomatic large fiber peripheral neuropathy diagnosed by a neurologist at a screening visit.
Age-related sensory changes on NCS without symptoms or mononeuropathy (refers to focal involvement of a single nerve, usually due to a local cause such as trauma, compression or entrapment) will not be excluded.
Participant has clinically significant underlying liver disease at Screening, or has any of the following:
Alanine Aminotransferase (ALT) \> 2 × upper limit of normal (ULN)
Aspartate aminotransferase (AST) \> 2 × ULN
Total bilirubin \> 1.5 × ULN
Alkaline phosphatase (ALP) \> 2 × ULN
ALT and AST are often higher than the normal range in Pompe disease patients. Participants whose liver laboratory tests fall outside the above ranges may be retested and, if the eligibility criteria are met on retesting, may be enrolled after confirmation by the Medical Monitor.
In addition, participants with abnormal laboratory results related to confirmed benign liver conditions including Gilbert's syndrome (defined by asymptomatic unconjugated hyperbilirubinemia \[17 to 70 µmol/L or 1 to 4 mg/dL\]) and asymptomatic gallstones, will be considered eligible for the study notwithstanding their abnormal laboratory results and may be enrolled.
Participant is currently on antiviral therapy for hepatitis B or C, or chronic/active hepatitis B or active hepatitis C evidenced by hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis B virus (HBV)-DNA positivity or hepatitis C virus (HCV)-RNA viral load positivity, respectively.
Negative viral load assays in 2 samples, collected at least 6 months apart, will be required to be considered negative. Both natural clearers and those who have cleared HCV on antiviral therapy are eligible. Participant has an active viral infection based on clinical observation.

Entiende la evaluación inicial

Tratamiento, grupos y participación

El registro puede describir tratamientos y duración sin incluir un calendario completo. Pide al equipo las visitas, procedimientos, riesgos, costos y alternativas. Mantén tu atención habitual salvo que tu médico te indique un cambio.

Asignación: Sin asignación al azar
Enmascaramiento: Sin enmascaramiento

Initial Dose Cohort

3x10\^13 vg/kg of AT845 administered via intravenous infusion

Genetic: zocaglusagene nuzaparvovec

Second Dose Cohort

6x10\^13 vg/kg of AT845 administered via intravenous infusion

Genetic: zocaglusagene nuzaparvovec

Third Dose Cohort

1x10\^14 vg/kg of AT845 administered via intravenous infusion

Genetic: zocaglusagene nuzaparvovec

zocaglusagene nuzaparvovec GENETIC

AT845 is an AAV8 vector delivering a functional copy of the human GAA gene, under the control of a muscle-specific promoter

Prepara tus preguntas

Qué evalúan los investigadores

Estas medidas indican qué se estudia. No prueban que un tratamiento funcione.

Medidas principales

Safety and Tolerability over time

Plazo: Up to month 120

Frequency of adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests

GAA enzymatic activity

Plazo: Baseline and Week 12

Change from baseline in GAA enzymatic activity in muscle biopsies at week 12

GAA protein expression

Plazo: Baseline and Week 12

Change from baseline in GAA protein expression in muscle biopsies at week 12.

Medidas secundarias

Vector Copy Number

Plazo: Baseline and Week 12

Change from baseline in vector copy number (VCN) in muscle biopsies at week 12

Thigh Fat Fraction

Plazo: Baseline and Month 18

Change from baseline in thigh fat fraction by MRI

6-Minute Walk Test (for ambulatory patients)