Anti-CD38 monoclonal antibody CM313 for primary immune thrombocytopenia: multicentre, randomised, placebo controlled, phase 2 trial

Abstract Objective To assess the efficacy and safety of CM313, an anti-CD38 monoclonal antibody, in adults with persistent or chronic primary immune thrombocytopenia. Design Multicentre, randomised, placebo controlled, phase 2 trial. Setting Five hospitals in China, 16 January to 11 June 2024. Participants 45 patients aged ≥18 years with persistent or chronic immune thrombocytopenia who failed to respond to, or relapsed after, glucocorticoid treatment but had previously responded to standard first line treatment. Interventions Patients were randomised to receive intravenous CM313 (16 mg/kg) or placebo weekly for eight weeks. Main outcome measures The primary outcome was overall response rate (at least two consecutive platelet counts ≥30×10 9 /L, a minimum doubling from baseline, and no bleeding) at week 8. A secondary outcome was time to the first two consecutive platelet counts ≥50×10 9 /L. Results Of 56 patients screened, 45 were randomised to receive CM313 (n=30) or placebo (n=15). At week 8, the overall response rate was higher in the CM313 group (83%; 25/30) compared with placebo group (20%; 3/15): difference 63.3% (95% confidence interval 33.7% to 81.3%; P<0.001). The median time to a platelet count of ≥50×10 9 /L was one week in the CM313 group but was not reached in the placebo group (P<0.001). The median cumulative response duration for platelet counts ≥50×10 9 /L was 18 weeks in the CM313 group versus three weeks in the placebo group (P=0.004). Treatment emergent adverse events occurred in 87% (26/30) of patients in the CM313 group and 80% (12/15) in the placebo group, with infusion related reactions and petechiae being the most common. Conclusion CM313 showed a favourable safety profile and encouraging efficacy in adults with persistent or chronic primary immune thrombocytopenia, characterised by rapid increase in platelet count, sustained platelet responses, and manageable adverse events. Trial registration ClinicalTrials.gov NCT06199089 .