Caplacizumab (CPLZ) is indicated, in combination with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST), for the treatment of immune-mediated TTP (iTTP). TPE is a mainstay of iTTP treatment but is burdensome and associated with complications. Real-world data suggest efficacy of TPE-free CPLZ regimens in iTTP, but clinical trial data is unavailable. This trial evaluates the efficacy and safety of CPLZ with IST without first-line TPE in adults with iTTP.

MAYARI (NCT05468320) is a Phase 3 multicenter study. Adults with a clinical diagnosis of initial/recurrent iTTP are eligible pending ADAMTS13 activity level confirmation within 48 hours of enrollment. Participants will receive CPLZ and IST. CPLZ treatment will be continued until ADAMTS13 activity level of ≥50% at 2 consecutive visits after platelet count normalization or for up to 12 weeks, whichever occurs first; follow-up period is 12 weeks. TPE may be started after 24 hours if indicated.

The primary endpoint is the proportion of participants achieving remission without requiring TPE during the overall study period (Table). Revised outcomes definitions from the International Working Group for iTTP will be utilized (Cuker et al. Blood. 2021;137[14]:1855-1861). An adequate number of participants will be enrolled to ensure ≥55 participants with ADAMTS13 activity levels <10% at baseline are available for primary endpoint analysis; around 61 participants are expected to be enrolled.

The current standard of care in patients with iTTP includes a combination of TPE, IST, and CPLZ. This novel study will define the efficacy and safety of CPLZ and IST without first-line TPE in adults with iTTP. This regimen would avert the risks for substantial complications associated with TPE and represents a paradigm shift in the frontline management of iTTP. This content was first presented at ASH 2022 (abstract #1174).