Resumen

El estudio RIN-PF-303 es un estudio multinacional diseñado para evaluar la superioridad del treprostinil inhalado frente a placebo en cuanto al cambio en la capacidad vital forzada (CVF) absoluta desde el valor basal hasta la semana 52.

Descripción detallada

El estudio RIN-PF-303 es un estudio multinacional, aleatorizado, doble ciego, controlado con placebo, para evaluar la superioridad del treprostinil inhalado frente a placebo en el cambio de la CVF absoluta en sujetos con FPI durante un período de 52 semanas. Los sujetos serán asignados aleatoriamente en proporción 1:1 para recibir treprostinil inhalado o placebo. Todos los sujetos iniciarán treprostinil inhalado o placebo a una dosis de 3 inhalaciones administradas 4 veces al día (QID) y titularán hasta un régimen de dosificación objetivo de 12 inhalaciones QID. Las dosis del medicamento del estudio podrán titularse según la tolerancia, hasta alcanzar la dosis objetivo o la dosis máxima clínicamente tolerada. Una vez habilitados, los sujetos deberán realizar 6 visitas al centro durante el Período de Tratamiento: en las semanas 4, 8, 16, 28, 40 y 52. Las evaluaciones de eficacia incluyen espirometría (CVF), tiempo hasta el deterioro clínico, tiempo hasta la primera exacerbación aguda de FPI, supervivencia global, cuestionario King's Brief Interstitial Lung Disease (K-BILD), concentración plasmática de péptido natriurético pro-cerebral N-terminal (NT-proBNP), uso de oxígeno suplementario y capacidad de difusión pulmonar (DLCO). Las evaluaciones de seguridad incluyen el desarrollo de eventos adversos (EA)/eventos adversos graves (EAG), signos vitales, parámetros de laboratorio clínico y parámetros de electrocardiograma (ECG). Los sujetos que completen la visita de la Semana 52 podrán tener la oportunidad de ingresar a un estudio de extensión abierto (OLE) tras completar la visita final del estudio.

Elegibilidad

Edad mínima: 40 YearsSexo: ALL

Criterios de inclusión

Subject gives voluntary informed consent to participate in the study.
Subject is ≥40 years of age, inclusive, at the time of signing informed consent.
The subject has a diagnosis of IPF based on the 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline (Raghu 2018) and confirmed by central review of high-resolution computed tomography (HRCT) (performed within the previous 12 months), and if available, surgical lung biopsy.
FVC ≥45% predicted at Screening.
Subjects on pirfenidone or nintedanib must be on a stable and optimized dose for ≥30 days prior to Baseline. Concomitant use of both pirfenidone and nintedanib is not permitted.
Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will abstain from intercourse (when it is in line with their preferred and usual lifestyle) or use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug.
Males with a partner of childbearing potential must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

Criterios de exclusión

Subject is pregnant or lactating.
Subject has primary obstructive airway physiology: FEV1/FVC \<0.70 at Screening.
The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy.
The subject has received any PAH-approved therapy, including prostacyclin therapy (epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), IP receptor agonists (selexipag), endothelin receptor antagonists, phosphodiesterase type 5 inhibitors (PDE5-Is), or soluble guanylate cyclase stimulators within 60 days prior to Baseline. As needed use of a PDE5-I for erectile dysfunction is permitted, provided no doses are taken within 48 hours of any study-related efficacy assessments.
Use of any of the following medications: azathioprine (AZA), cyclosporine, mycophenolate mofetil, tacrolimus, oral corticosteroids (OCS) \>20 mg/day or the combination of OCS+AZA+N-acetylcysteine within 30 days prior to Baseline; cyclophosphamide within 60 days prior to Baseline; or rituximab within 6 months prior to Baseline.
The subject is receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
Exacerbation of IPF or active pulmonary or upper respiratory infection within 30 days prior to Baseline. Subjects must have completed any antibiotic or steroid regimens for treatment of the infection or acute exacerbation more than 30 days prior to Baseline to be eligible. If hospitalized for an acute exacerbation of IPF or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible.
Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
In the opinion of the Investigator, the subject has any condition that would interfere with the interpretation of study assessments or would impair study participation or cooperation.
Use of any other investigational drug/device or participation in any investigational study in which the subject received a medical intervention (ie, procedure, device, medication/supplement) within 30 days prior to Screening. Subjects participating in non-interventional, observational, or registry studies are eligible.
Life expectancy \<6 months due to IPF or a concomitant illness.
Acute pulmonary embolism within 90 days prior to Baseline.

Ubicaciones

CINME S.A. - Centro de Investigaciones Metabolicas

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Centro Medico Dra. De Salvo

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Instituto Ave Pulmo - Fundación enfisema

Mar del Plata, Buenos Aires, Argentina

Sanatorio Allende S.A.

Córdoba, Córdoba Province, Argentina

Instituto Médico Río Cuarto

Río Cuarto, Córdoba Province, Argentina

Centro Médico INSARES

Mendoza, Mendoza Province, Argentina

Sanatorio Parque - Consultorios Externos

Rosario, Santa Fe Province, Argentina

Centro Integral de Medicina Respiratoria

San Miguel de Tucumán, Tucumán Province, Argentina

Investigaciones en Patologías Respiratorias