A Phase 2 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of KER-050 as Monotherapy or in Combination with Ruxolitinib in Participants with Myelofibrosis
Criterios clave de inclusión:
Hombre o mujer ≥18 años de edad, en el momento de firmar el consentimiento informado.
Diagnóstico de PMF, MF post-PV o MF post-ET según los criterios de la Organización Mundial de la Salud de 2017.
Criterios específicos de cada brazo:
Brazo 1A:
Tratados previamente con inhibidores de JAK o el participante no es elegible para inhibidores de JAK
Anemia, definida como hemoglobina ≤10 g/dL durante el cribado, o recibir transfusiones de glóbulos rojos
Brazo 2A:
Tratado previamente con inhibidor(es) de JAK o el participante no es elegible para inhibidor(es) de JAK
Anemia, definida como hemoglobina ≤10 g/dL durante el cribado, o que recibe transfusiones de glóbulos rojos
Criterios específicos del brazo para 1B y 2B:
Ha estado recibiendo ruxolitinib durante ≥8 semanas antes del C1D1 y con una dosis estable durante ≥4 semanas antes del C1D1.
Anemia, definida como hemoglobina ≤10 g/dL durante el cribado, o recibir transfusiones de glóbulos rojos.
presence of the following heart conditions
New York Heart Association class 3 or 4 heart failure
QTcF >500 msec on screening electrocardiogram (ECG) or C1D1
Clinically significant uncontrolled arrhythmia (participants with rhythm-controlled atrial fibrillation are not excluded)
Acute myocardial infarction or unstable angina pectoris <6 months before C1D1
History of stroke, deep vein thrombosis, or arterial embolism in the 6 months prior to C1D1.
Any malignant tumor other than PMF, post-ET MF or post-PV MF that was not in remission and/or required systemic therapy, including radiation, chemotherapy, hormonal therapy or surgery, within 1 year prior to C1D1. Cancers in situ, squamous cell and basal cell carcinomas that have been completely excised, and monoclonal gammopathy of uncertain significance are allowed at the discretion of the investigator.
History of solid organ or hematologic transplantation.
Presence of uncontrolled hypertension, defined as systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg despite adequate treatment.
Diagnosis of hemolytic anemia, active hemorrhage, hemoglobinopathies, or congenital disorders as a cause of the participant's anemia.
CTCAE grade ≥2 hemorrhagic events in the 3 months prior to C1D1.
Bone marrow blast percentage >2%. Participants with a blast percentage between 2 and 5% are allowed if at least 2 bone marrows with a 6-month interval demonstrate stability of the blast percentage, these participants must be reviewed with the Medical Monitor prior to study entry.
Prior treatment with luspatercept, sotatercept or other commercially available or investigational TGF-β inhibitors (all arms).
Treatment within 28 days prior to C1D1.
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Se trata de un estudio de fase 2, multicéntrico y abierto para evaluar la seguridad y la eficacia de KER-050 como monoterapia o en combinación con ruxolitinib en participantes con mielofibrosis.
