Resumen

El estudio RIN-PF-305 está diseñado para evaluar la seguridad y eficacia de treprostinil inhalado en sujetos con fibrosis pulmonar progresiva (PPF) durante un período de 52 semanas.

Descripción detallada

El estudio RIN-PF-305 es un estudio de fase 3, multinacional, aleatorizado, doble ciego, controlado con placebo, para evaluar la seguridad y eficacia de treprostinil inhalado en sujetos con PPF 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 fármaco del estudio podrán incrementarse según tolerancia, hasta alcanzar la dosis objetivo o la dosis máxima tolerada clínicamente. Una vez elegibles, se requerirán 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 (capacidad vital forzada [CVF]), tiempo hasta el empeoramiento clínico, tiempo hasta la primera exacerbación aguda de la enfermedad pulmonar intersticial (EPI), supervivencia global, cuestionario King's Brief Interstitial Lung Disease (K-BILD), concentración plasmática de péptido natriurético cerebral N-terminal pro (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 electrocardiográficos (ECG). Los sujetos que completen la visita de la semana 52 podrán tener la oportunidad de participar en un estudio de extensión abierto (OLE) tras completar la visita final del estudio.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Subject gives voluntary informed consent to participate in the study.
Subject is ≥18 years of age, inclusive, at the time of signing informed consent.
Subject has radiological evidence of pulmonary fibrosis of \>10% extent on an HRCT scan in the previous 12 months (confirmed by central review).
Subject has a diagnosis of PPF (other than IPF) that fulfills at least 1 of the following criteria for progression within 24 months of screening despite standard treatment of ILD, as assessed by the Investigator:
Clinically significant decline in % predicted FVC based on ≥10% relative decline
Marginal decline in % predicted FVC based on ≥5% to \<10% relative decline combined with worsening of respiratory symptoms
Marginal decline in % predicted FVC based on ≥5% to \<10% relative decline combined with increasing extent of fibrotic changes on chest imaging
Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging
FVC ≥45% predicted at Screening (confirmed by central review).
Subjects must be on 1 of the following:
On nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, are planning to continue treatment through the study
Not on treatment with nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, not planning to initiate either treatment during the study.
Concomitant use of both nintedanib and pirfenidone is not permitted.
Subjects treated with immunosuppressive agents (eg, mycophenolate, methotrexate, azathioprine, oral corticosteroids, rituximab) need to be on treatment for at least 120 days prior to Baseline and, in the Investigator's clinical opinion, must be refractory to treatment.
Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will agree to do 1 of the following:
Abstain from intercourse (when it is in line with their preferred and usual lifestyle)
Use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug.
i. Medically acceptable, highly effective forms of contraception can include approved hormonal contraceptives (oral, injectable, and implantable) and barrier methods (such as a condom or diaphragm) when used with a spermicide.
Women who are successfully sterilized (including hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for at least 12 consecutive months) are not considered to be of reproductive potential.
Males with a partner of childbearing potential must agree to 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 (forced expiratory volume in 1 second/FVC \<0.70 at Screening) or greater extent of emphysema than fibrosis on HRCT (confirmed by central review).
Subject has a diagnosis of IPF.
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.
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), soluble guanylate cyclase stimulators, or activin signaling inhibitors (sotatercept) 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 prior to any study-related efficacy assessments.
Subject is receiving \>10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
Exacerbation of ILD 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 ILD or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible.
Subject has uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
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.
Acute pulmonary embolism within 90 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.
In the opinion of the Investigator, life expectancy \<12 months due to ILD or a concomitant illness.
Subject has received nerandomilast within 60 days prior to Baseline.

Ubicaciones

Instituto Ave Pulmo - Fundacion enfisema

Mar del Plata, Buenos Aires, Argentina

Mario Fernando Sabas · fsabas@gmail.com · (223) 410-8383

RECRUITING

Instituto Medico Rio Cuarto

Río Cuarto, Córdoba Province, Argentina

Sebastián Etchevers · sebastianet@gmail.com · +5491131077237

RECRUITING

Sanatorio Parque de Rosario - Consultorios Externos

Rosario, Santa Fe Province, Argentina

Julieta Nasurdi · julinasurdi99@gmail.com · +543414200222

RECRUITING

Investigaciones en Patologias Respiratorias

San Miguel de Tucumán, Tucumán Province, Argentina

Maria Jose Guzman · ipr_mariajose@yahoo.com.ar · +543814212611

RECRUITING

CIMER-Centro Integral de Medicina Respiratoria

San Miguel de Tucumán, Tucumán Province, Argentina

Natalia Juarez Babiano · nataliajuarezbabiano1@gmail.com · +543812577481

RECRUITING

CINME Centro de Investigaciones Metabolicas

Buenos Aires, Argentina

Yesica Castillo · ycastillo@cinme.com.ar · +541150319915

RECRUITING

Fundación Respirar

Buenos Aires, Argentina

Antonela Iannazzo · iannazzoantonela@gmail.com · +541170781548 ext

RECRUITING

Instituto de Medicina Respiratoria

Córdoba, Argentina

Angélica Baima · abaima@damic.com.ar · +543514888200

RECRUITING

Sanatorio Allende Cerro

Córdoba, Argentina

Maria Gracia de la Vega · mgdelavega@sanatorioallende.com · +54351269200

RECRUITING

Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo, multinacional, para evaluar la eficacia y seguridad de treprostinil inhalado en sujetos con fibrosis pulmonar progresiva (TETON-PPF)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Placebo

Inhaled Treprostinil

Treprostinil Ultrasonic Nebulizer

Ubicaciones

Instituto Ave Pulmo - Fundacion enfisema

Instituto Medico Rio Cuarto

Sanatorio Parque de Rosario - Consultorios Externos

Investigaciones en Patologias Respiratorias

CIMER-Centro Integral de Medicina Respiratoria

CINME Centro de Investigaciones Metabolicas

Fundación Respirar

Instituto de Medicina Respiratoria

Sanatorio Allende Cerro

Patrocinadores

Contactos

United Therapeutics Global Medical Information