Resumen

El propósito de este ensayo clínico es estudiar la seguridad y los efectos del medicamento en investigación (llamado fosmanogepix) para el posible tratamiento de la candidemia y/o la candidiasis invasiva, una infección fúngica potencialmente mortal causada por varias especies de levadura del género Candida. El estudio busca pacientes con diagnóstico de candidemia y/o candidiasis invasiva. Dos tercios de los pacientes recibirán el medicamento en investigación fosmanogepix en infusión intravenosa (IV) seguida de comprimidos orales opcionales de fosmanogepix. Un tercio de los pacientes recibirá un régimen de atención estándar con infusión intravenosa (IV) de caspofungina seguida de cápsulas orales opcionales de fluconazol. Fosmanogepix o caspofungina se administrarán primero como infusión intravenosa (IV) directamente en una vena del brazo, una vez al día en la clínica del estudio. Los comprimidos de fosmanogepix o las cápsulas de fluconazol se tomarán por vía oral diariamente, ya sea en la clínica del estudio o en el domicilio si el paciente está suficientemente bien como para recibir el alta hospitalaria. Se comparará el efecto del tratamiento en los pacientes que reciben fosmanogepix con el de quienes reciben caspofungina/fluconazol. El objetivo principal es demostrar que fosmanogepix no es inferior (no es peor) a caspofungina/fluconazol con un margen de no inferioridad del 15%. La duración del tratamiento del estudio y el número de visitas variarán en función del tiempo que dure el tratamiento de la infección. El tratamiento continuará durante un máximo de 6 semanas, dependiendo de cuándo se resuelva la infección y de si otros síntomas relacionados con ella hayan mejorado. También habrá una visita de seguimiento 6 semanas después de finalizar el tratamiento del estudio.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Patients ≥ 18 years (or the minimum country-specific age of consent if \> 18) at Screening who have provided signed informed consent indicating that they understand the purpose of, and procedures required for, the study, and are willing to participate in the study. If the patient is unable to consent for himself/herself, a legally authorized representative must provide informed consent on his/her behalf.
Diagnosis of candidemia and/or invasive candidiasis based on a blood or non-blood specimen obtained within ≤ 96 hours (4 days) before randomization, and on clinical criteria judged attributable to candidemia/invasive candidiasis occurring at any time from ≤ 12 hours prior to the qualifying positive index culture being taken through to randomization.
Patient's condition allows for appropriate infection source control measures, including removal of pre-existing intravascular catheters and devices, if necessary.

Criterios de exclusión

Existing infection
Infection known to be due to Candida krusei, in blood or any other normally sterile site.
Inappropriate fungal infection source control.
Diagnosis of certain deep-seated Candida infections.
Life expectancy of \< 72 hours in the opinion of the investigator.
Requirement, or expected requirement, for hemodialysis, peritoneal dialysis, or hemofiltration.
Ongoing neurological disorders, including specified conditions presenting with a CTCAE Grade ≥ 2 (neurological symptoms that are considered to be a consequence of the current episode of candidemia / invasive candidiasis are not exclusionary).
Patients with known human immunodeficiency virus infection, who have CD4+ count \< 200/mm3 or viral load \> 400 copies/mL), or who have had an active opportunistic infection within 6 months prior to Screening.
Other medical or psychiatric condition or laboratory abnormality that may increase the risk of study participation or make the patient inappropriate for the study.
Current use of any prohibited concomitant medications or those unwilling/unable to use a permitted concomitant medication.
Received \> 2 days (\> 48 hours) equivalent of prior systemic antifungal treatment at approved doses and frequency to treat the current episode of candidemia and/or invasive candidiasis (e.g., \> 2 doses of a once daily antifungal agent or \> 4 doses of a twice daily antifungal agent), within the 96 hours prior to randomization (except for non-susceptible Candida spp. and for patients who develop candidemia or invasive candidiasis while on prophylaxis with an azole or amphotericin B).
Previous administration with an investigational drug or investigational vaccine within 30 days or 5 half-lives preceding the first dose of study drug used in this study (whichever is longer).
Prior participation in this or any previous study of fosmanogepix.
Moderate or severe hepatic impairment, known active viral hepatitis B or C, ALT or AST ≥ 5 × ULN or total bilirubin \> 3 × ULN unless this is due to isolated hyperbilirubinemia or documented Gilbert's syndrome.
Female patient is pregnant or lactating.
Known hypersensitivity to fosmanogepix, manogepix, caspofungin, any echinocandin, fluconazole or to any of their excipients.
Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and Sponsor and Sponsor delegate employees directly involved in the conduct of the study and their family members.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Fosmanogepix

Fosmanogepix

Caspofungin

Fluconazole

Placebo

Placebo

Placebo

Placebo

Ubicaciones

Central Hospital de San Isidro Melchor Posse

Buenos Aires Italian Hospital, Department of Infectious Diseases

Cordoba Private University Hospital, Department of Infectious Diseases

Italian Hospital of La Plata, Department of Infectious Diseases

Central Hospital Mendoza

British Sanatorium SA

Patrocinadores

Contactos

Manuel Häckl, MD

Marc Engelhardt, MD