This study is designed as a Phase Ib/II trial. The phase Ib cohort will enroll patients with severe aplastic anemia (SAA) who have failed to respond to intensified immunosuppressive therapy. In contrast, the phase II cohort will include newly diagnosed and treatment-naïve patients with SAA. A Safety Review Committee (SRC), chaired by the principal investigators, will be established to oversee patient safety throughout the study. Suppose the Phase Ib results demonstrate acceptable safety and tolerability. In that case, the data will be submitted to the Ethics Committee for review, and, upon approval, the study will advance to Phase II.
Phase Ib uses a 3+3 dose-escalation design with two cohorts: 150 mg golidocitinib orally every other day (low dose) or once daily (high dose). Phase II is a single-arm trial with Simon's two-stage optimal design.
According to the Chinese Guidelines for the Diagnosis and Treatment of Aplastic Anemia (2022 Edition) and the Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline (Br J Haematol. 2024; 204: 784-804), the patient is diagnosed with primary acquired AA and meets the diagnostic criteria for SAA.
Subjects received intensive immunosuppressive therapy combined with a standard-dose TPO receptor agonist for at least 4 months but failed to respond or experienced relapse.
Unsuitable for or unwilling to undergo allogeneic hematopoietic stem cell transplantation and lacking other superior treatment options.
Age ≥ 18 years
Presence of any other primary or secondary bone marrow failure syndrome, including but not limited to Fanconi anemia, myelodysplastic syndrome (MDS), clonal cytopenia of undetermined significance, or large granular lymphocytic leukemia.
Bone marrow reticulin fibrosis ≥ grade 2
Subjects with a paroxysmal nocturnal hemoglobinuria (PNH) clone ≥ 50% or with evidence of active hemolysis.
Presence of clonal cytogenetic abnormalities characteristic of MDS, excluding +8, del(20q), and -Y.