Resumen

El ensayo ASPIRE es un ensayo clínico aleatorizado, doble ciego, controlado con placebo, de grupos paralelos y multicéntrico de 52 semanas, en el que se evalúan la eficacia, seguridad y farmacocinética de buloxibutid administrado por vía oral, ya sea como complemento de la terapia estable para FPI o como monoterapia, en participantes con FPI. Sitio web del ensayo: www.aspire-ipf.com

Descripción detallada

Buloxibutid es un agonista oral del receptor de angiotensina II tipo 2 (AT2) que ha demostrado mejorar la función pulmonar en la FPI durante 36 semanas. Buloxibutid agoniza el receptor AT2 en las células epiteliales alveolares tipo 2 (AEC2), que se cree desempeñan un papel central en la enfermedad. Se ha demostrado preclínicamente que buloxibutid mejora la viabilidad de las AEC2, la integridad alveolar mediante la secreción de surfactante y la reparación epitelial mediante la reposición de células epiteliales alveolares tipo 1 (AEC1) para el intercambio gaseoso. Esto conduce a la disminución de la señalización profibrótica posterior, al potenciamiento de la resolución del tejido fibrótico existente mediante la regulación positiva de las metaloproteinasas de la matriz colagenasa, y a la corrección de la disfunción vascular asociada con la enfermedad. El ensayo incluirá participantes que se encuentren en tratamiento estable con terapia aprobada para FPI o que actualmente no estén recibiendo tratamiento con una terapia aprobada para FPI. Este último grupo incluirá participantes intolerantes o sin respuesta a las terapias aprobadas para FPI, participantes que no sean elegibles para recibir dichas terapias, y participantes que hayan declinado voluntariamente recibir una terapia aprobada para FPI después de haber sido completamente informados de los beneficios y riesgos potenciales de dicha terapia. Debido al riesgo potencial de interacciones farmacológicas (DDI), el tratamiento concomitante con pirfenidona no está permitido en este ensayo. Los participantes que no estén en tratamiento antifibrótico al inicio del estudio podrán iniciar dicho tratamiento durante el estudio. Se planea inscribir 360 participantes en el ensayo: 120 participantes con buloxibutid oral 100 mg BID, 120 participantes con buloxibutid oral 50 mg BID y 120 participantes con placebo oral BID durante 52 semanas. El tratamiento será ciego y la asignación al tratamiento será aleatorizada. La medición primaria se basará en la espirometría, midiendo la capacidad vital forzada (CVF). El ensayo consta de 3 períodos consecutivos: un período de selección de hasta 6 semanas, un período de tratamiento de 52 semanas y un período de seguimiento de 2 a 4 semanas después de la visita de la semana 52. Los procedimientos del estudio han sido planificados con el foco puesto en optimizar la comodidad del paciente, manteniendo una conducción segura y un rigor científico estricto. Sitio web del ensayo: www.aspire-ipf.com

Elegibilidad

Edad mínima: 40 YearsSexo: ALL

Criterios de inclusión

Age ≥ 40 years at the time of signing the informed consent.
Diagnosed with IPF within 7 years prior to visit 1, as per applicable ATS/ERS/JRS/ALAT guidelines at the time of diagnosis.
HRCT scan within 36 months prior to visit 1 with central reading confirming either a or b, and c
A pattern consistent with usual interstitial pneumonia (UIP) according to ATS/ERS/JRS/ALAT 2022 guideline (Raghu et al., 2022) UIP or probable UIP.
A pattern indeterminate for UIP according to ATS/ERS/JRS/ALAT 2022 guidelines (Raghu et al., 2022) and a historical biopsy (surgical lung biopsy or transbronchial lung cryobiopsy) consistent with IPF.
Extent of fibrosis \> extent of emphysema.
FVC ≥50% predicted at visit 1.
DLCO (corrected for hemoglobin) ≥30% predicted at visit 1.
Either:
On a stable dose of licensed IPF therapy for at least 8 weeks prior to visit 1 and expected to remain on this background treatment after randomization. Due to the risk of DDIs, concomitant treatment with pirfenidone is not allowed in this trial.
Not currently receiving treatment for IPF with a licensed therapy for any reason, including prior intolerance, non-responsiveness, ineligibility, lack of access or voluntarily decline. Any such previous treatment must have been discontinued \>8 weeks prior to visit 1.
Anticipated life expectancy of at least 12 months at visit 1 and not anticipated to require a lung transplant during the trial period (being on a transplant list does not exclude a participant from the trial).
Contraceptive use by women of childbearing potential (WOCBP) which is highly effective and consistent with local regulations regarding the methods of contraception for those participating in clinical trials.
For UK and countries within the EU: Male participants, if heterosexually active with a female partner of childbearing potential, or a pregnant or breastfeeding partner, must agree to use barrier contraception (male condom) and abstain from sperm donation for the duration of the treatment period and for at least 2 weeks after the last dose of the trial drug.
Written informed consent, consistent with ICH-GCP and local laws, obtained before the initiation of any trial-related procedure.

Criterios de exclusión

Participants are excluded from the trial if any of the following criteria apply:
Concurrent serious medical condition that in the opinion of the investigator constitutes a risk or a contraindication for participation in the trial or that could interfere with the trial objectives, conduct or evaluation, including active or suspected malignancy or history of malignancy within 5 years prior to visit 1, except appropriately treated basal cell carcinoma of the skin, fully resected and cured squamous cell carcinoma of the skin, "under surveillance" prostate cancer or in situ carcinoma of uterine cervix.
Airways obstruction with a pre-bronchodilator forced expiratory volume in one second (FEV1)/FVC ratio \<0.7 at visit 1.
Lower respiratory tract infection requiring antibiotics and not fully recovered according to investigator judgement within 4 weeks prior to visit 2.
Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring hospitalization and not fully recovered according to investigator judgement within 4 weeks prior to visit 2.
Known impaired hepatic function or clinically significant liver disease (Child-Pugh B or C hepatic impairment), or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper limit of normal (ULN) or total bilirubin \>1.5 times ULN at visit 1.
Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR) ≤35 ml/min/1.73 m2 at visit 1 according to Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula).
Prolonged QTcF (QT interval with Fridericia's correction) (\>450 ms), AV-block II or III, uncontrolled arrhythmia, or other clinically significant abnormality in the resting ECG at visit 1, as judged by the investigator. Patients with implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time may be enrolled in the trial based upon investigator judgement, following cardiologist consultation if deemed necessary, and only after discussion with the medical monitor.
Heart failure NYHA Class IV, acutely decompensated right heart failure, PH with syncopal episode, confirmed myocardial infarction, unstable angina or uncontrolled hypertension, within 6 months prior to visit 1.
Known hypersensitivity or intolerance to buloxibutid or to any other components of the test product, including excipients.
Pregnant or breast-feeding female participants.
Acute IPF exacerbation within 3 months prior to visit 1 and/or during the screening period, as defined by Collard et al., 2016:
Acute worsening or development of dyspnea typically \<1 month duration.
Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern (if no previous computed tomography is available, the qualifier "new" can be dropped).
Deterioration not fully explained by cardiac failure or fluid overload.
Inability to generate a spirometry test at visit 1 meeting the standards of the ATS/ERS 2019 guideline (Graham et al., 2019).
Treatment with pirfenidone within 8 weeks prior to visit 1 or anticipated need for pirfenidone during participation in the trial.
Trial website: www.aspire-ipf.com

RECRUITING

Ibamedica

Santa Fe, Argentina

Martin Maillo, MD

RECRUITING

Ensayo Clínico de Fase III, Aleatorizado, Doble Ciego, Controlado con Placebo, de Grupos Paralelos y Multicéntrico para Evaluar la Eficacia y Seguridad de 2 Dosis de Buloxibutid durante 52 Semanas en Personas con Fibrosis Pulmonar Idiopática.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Buloxibutid

Placebo

Ubicaciones

Research Institute of Respiratory Diseases

CEMER Medical Center for Respiratory Diseases

Belgrano Clinical Research Center

CINME - Metabolic Research Center

Medical Center Dra. De Salvo

IMER Respiratory Medicine Institute

Breathe Comprehensive Clinical Health

Emphysema Foundation, Pneumology

Vistalba Health Center

InnovaCiencia

Ibamedica

Patrocinadores

Contactos

Thomas Eskildsen, MSc. Pharm.

Bernt Van Den Blink, MD