Resumen

El estudio ROR-PH-301, ADVANCE OUTCOMES, está diseñado para evaluar la eficacia y seguridad de ralinepag añadido al tratamiento estándar para hipertensión arterial pulmonar (HAP) o al tratamiento específico de base para HAP en sujetos con HAP Grupo 1 de la Organización Mundial de la Salud (OMS).

Descripción detallada

El estudio ROR-PH-301 es un estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo. Los sujetos que cumplan los criterios de ingreso serán asignados aleatoriamente en proporción 1:1 para recibir ralinepag o placebo, además de su tratamiento estándar o tratamiento específico de base para HAP, según corresponda. El criterio de valoración primario es el tiempo (en días) desde la aleatorización hasta el primer evento de empeoramiento clínico definido por protocolo y adjudicado. Todos los eventos del criterio de valoración primario serán adjudicados por un Comité Independiente de Eventos Clínicos (CEC) de forma ciega. Los sujetos que presenten un evento del criterio de valoración primario confirmado y adjudicado por el CEC en cualquier momento durante el estudio, y todos los sujetos en tratamiento al concluir el estudio que hayan completado la visita de la semana 28 (después de alcanzar el número objetivo de eventos confirmados), tendrán la opción de inscribirse en un estudio de extensión abierto (EEA). Los sujetos que no elijan participar en el EEA suspenderán el fármaco del estudio y deberán permanecer en el estudio para el seguimiento a largo plazo del estado de supervivencia, y recibirán tratamiento estándar para HAP, a criterio del médico tratante.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

At least 18 years of age.
Evidence of a personally signed and dated informed consent form indicating that the subject has been informed of all pertinent aspects of the study prior to initiation of any study-related procedures.
Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Primary diagnosis of symptomatic PAH.
Has had a right heart catheterization (RHC) performed at or within 3 years prior to Screening (RHC will be performed during Screening if not available) that is consistent with the diagnosis of PAH.
Has WHO/ NYHA functional class II to IV symptoms.
If on PAH-specific background oral therapy, subject is on stable therapy with either an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE5-I) or a soluble guanylate cyclase (sGC) stimulator.
Has a 6MWD of ≥150 meters.
If taking concomitant medications that may affect the clinical manifestations of PAH (eg, calcium channel blockers, diuretics, digoxin, or L arginine supplementation, beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers), must be on a stable dose for at least 30 days prior to the Baseline Visit and the dosage maintained throughout the study. The exception is that the dose of diuretics must be stable for at least the 10 days prior to Baseline.
Both male and female subjects agree to use a highly effective method of birth control throughout the entire study period from informed consent through to the 30-Day Follow-up Visit, if the possibility of conception exists. Eligible male and female subjects must also agree not to participate in a conception process during the study and for 30 days after the last dose of IMP. Eligible male subjects must agree not to participate in sperm donation for 90 days after the last dose of IMP.

Criterios de exclusión

For subjects with known HIV-associated PAH, a cluster designation 4 (CD4+) T-cell count \<200/mm3 within 90 days of Baseline.
Must not have 3 or more left ventricular dysfunction risk factors as defined in the study protocol.
Has evidence of more than mild lung disease on pulmonary function tests performed within 180 days prior to, or during Screening.
Has evidence of thromboembolic disease as determined by a V/Q lung scan or local standard of care diagnostic evaluation at or after diagnosis of PAH.
Current diagnosis of ongoing and clinically significant sleep apnea as defined by the Investigator.
Male subjects with a corrected QT interval using Fridericia's formula (QTcF) \>450 msec and female subjects with a QTcF \>470 msec on ECG recorded at Screening and analyzed by the central ECG laboratory. Subjects with evidence of intraventricular conduction delay, defined as a QRS interval greater than 110 msec, will be excluded if the QTcF is \>500 msec for both males and females.
Severe chronic liver disease (ie, Child-Pugh Class C), portal hypertension, cirrhosis or complications of cirrhosis/portal hypertension (eg, history of variceal hemorrhage, encephalopathy).
Confirmed active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
Subjects with alanine aminotransferase or aspartate aminotransferase ≥3 times the upper limit of normal (ULN) or total bilirubin ≥2 × ULN at Screening.
Chronic renal insufficiency as defined by serum creatinine \>2.5 mg/dL or requiring dialysis at Screening.
Hemoglobin concentration \<9 g/dL at Screening.
Subjects treated with an IV or SC prostacyclin pathway agent (eg, epoprostenol, treprostinil, or iloprost) or activin signaling inhibitor for PAH at any time prior to Baseline (use in vasoreactive testing is permitted).
Subjects currently on or who were treated with an inhaled or oral prostacyclin pathway agent (iloprost, treprostinil, beraprost, or selexipag) for \>6 months or within 90 days prior to Baseline.
Subject has pulmonary veno-occlusive disease.
Malignancy diagnosed and/or treated within 5 years prior to Screening, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent.
Subject tests positive for amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine or phencyclidine in urine drug screen performed at Screening, or has a recent history (6 months) of alcohol or drug abuse. A subject will not be excluded due to a positive drug screen caused by prescribed medications.
Initiation or discontinuation of a cardio-pulmonary rehabilitation program based upon exercise within 90 days prior to Screening and/or planned during study participation.
Prior participation in any study of ralinepag or participation in another interventional clinical study with medicinal products within 30 days prior to Screening. Concurrent participation in registry or observational studies is allowed, as long as the subject can fulfill all other entry criteria and comply with all study procedures.
Any reason that, in the opinion of the Investigator or Medical Monitor, precludes the subject from participating in the study (eg, any previous or intercurrent medical condition) that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation.
Known hypersensitivity to ralinepag or any of the excipients.
Life expectancy \<12 months based on the Investigator's opinion.
Women who are pregnant, lactating or breast-feeding.

Ubicaciones

Sanatorio de la Trinidad Mitre

Buenos Aires, Buenos Aires, Argentina

Hospital Italiano

Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Mar del Plata

Mar del Plata, Buenos Aires, Argentina

Cardiologia Palmero

Caba, Buenos Aires F.D., Argentina

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

Fundacion Respirar

Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

Fundacion Favaloro

Ciudad Autonoma Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

Instituto de Cardiologia de Corrientes

Corrientes, Corrientes Province, Argentina

Hospital Privado Centro Medico de Cordoba S.A

Córdoba, Córdoba Province, Argentina

Sanatorio Parque

Rosario, Santa Fe Province, Argentina

Hospital PROVINCIAL "Dr. Jose Maria Cullen"

Santa Fe, Santa Fe Province, Argentina

Hospital Italiano de Cordoba

Córdoba, Argentina

Estudio fase 3, aleatorizado, doble ciego, controlado con placebo, para evaluar la eficacia y seguridad de ralinepag añadido al tratamiento estándar o al tratamiento específico de base para HAP en sujetos con HAP Grupo 1 de la OMS

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Ralinepag

Placebo

Ubicaciones

Sanatorio de la Trinidad Mitre

Hospital Italiano

Instituto de Investigaciones Clinicas Mar del Plata

Cardiologia Palmero

Hospital Britanico de Buenos Aires

Fundacion Respirar

Fundacion Favaloro

Instituto de Cardiologia de Corrientes

Hospital Privado Centro Medico de Cordoba S.A

Sanatorio Parque

Hospital PROVINCIAL "Dr. Jose Maria Cullen"

Hospital Italiano de Cordoba

Patrocinadores