Resumen

Se trata de un estudio paralelo de fase 3 con dos brazos para el tratamiento de la EICHc moderada o grave de diagnóstico reciente. La duración del estudio para cada participante incluye: hasta 4 semanas de cribado; un período de tratamiento hasta la progresión clínicamente significativa de la EICHc (definida como la progresión que requiere la adición de un nuevo tratamiento sistémico para la EICHc), la recaída o recurrencia de la enfermedad subyacente, el inicio de un nuevo tratamiento sistémico para la EICHc por parte del participante, la aparición de una toxicidad inaceptable, la solicitud del participante o del investigador, o hasta que se alcance el fin del estudio, lo que ocurra primero; al menos 30 días de seguimiento de eventos adversos (EA) tras la última dosis hasta su resolución o estabilización, según corresponda; y seguimiento a largo plazo hasta la muerte o el cierre del estudio, lo que ocurra primero.

Descripción detallada

Hasta 2,5 años.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

Patients must be at least 12 years of age inclusive, at the time of signing the informed consent
Participants who have undergone allogenic HCT with newly diagnosed moderate to severe cGVHD according to NIH consensus diagnosis and staging criteria (2014)
Participants who require systemic treatment with corticosteroids for cGVHD
Participants who have not received any prior systemic treatment for cGVHD (including ECP)
If participants are receiving other immunosuppressive agents for the prophylaxis or treatment of acute GVHD, the dose should be under the threshold pre-defined in protocol
For adult participants, the body weight should be ≥40 kg. For adolescent participants, the body weight should be ≥30 kg
Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Participants or their legally authorized representative must be capable of giving signed informed consent

Criterios de exclusión

Participants are excluded from the study if any of the following criteria apply:
Medical conditions
Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of progressive or relapsed underlying disease after the most recent allogeneic HCT
Post-transplant lymphoproliferative disease within 4 weeks prior to randomization
Female participants who are pregnant or breastfeeding
Unable to tolerate a prednisone equivalent dose of corticosteroids ≥ 1 mg/kg/day Prior/concomitant therapy
Participant has had previous exposure to belumosudil.
Received any previous systemic treatment for cGVHD with the following exception: Corticosteroids for cGVHD received within 7 days prior to the planned administration of IMP only if in the interest of participant.
Prior/concurrent clinical study experience
Received any investigational agents, or any investigational device or procedure, or prohibited therapy for this study within 28 days or 5 elimination half-lives prior to randomization, whichever is longer Diagnostic assessments
Karnofsky (if aged ≥16 years)/Lansky (if aged \<16 years) Performance Score of \< 60
Platelets \<25 x 109/L. Platelet transfusion is not allowed within 3 days before the screening hematological test
Absolute neutrophil count (ANC) \<0.5 x 109/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening
Estimated Glomerular Filtration Rate (eGFR) \<30 mL/min/1.73 m2 using the MDRD-4 variable formula (if aged ≥18 years) or using the Bedside Schwartz formula (if aged \<18 years)
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>3 x ULN without liver cGVHD or\>5 × ULN with liver) cGVHD
Total bilirubin \>1.5 × (ULN) (\>3 × ULN if Gilbert syndrome)
Participant has forced expiratory volume in 1 second (FEV1) of predicted ≤39% or has lung score of 3 according to NIH consensus diagnostic and staging criteria (2014)
History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease)
Known history of human immunodeficiency virus (HIV)
Active viral disease including hepatitis B virus (HBV) or hepatitis C virus (HCV)
Active uncontrolled cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection worsening are present according to Investigator's judgement
Diagnosed or treated for another malignancy other than the underlying disease allogeneic HCT was indicated for, within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy
Unable to swallow tablets
Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
Any active, uncontrolled infections assessed to be clinically significant by the Investigator

Ubicaciones

Investigational Site Number : 0320006

Pilar, Buenos Aires, Argentina

Investigational Site Number : 0320005

Buenos Aires, Argentina

Investigational Site Number : 0320003

Buenos Aires, Argentina

Investigational Site Number : 0320001

Buenos Aires, Argentina

Investigational Site Number : 0320002

Buenos Aires, Argentina

Investigational Site Number : 0320004

Córdoba, Argentina

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Belumosudil

Placebo

Prednisone

Prednisolone

Ubicaciones

Investigational Site Number : 0320006

Investigational Site Number : 0320005

Investigational Site Number : 0320003

Investigational Site Number : 0320001

Investigational Site Number : 0320002

Investigational Site Number : 0320004

Patrocinadores