The Capla 1000+ Project

• Pivotal, phase 3, double-blind, randomized control trial of 145 adult patients with aTTP/iTTP
• Patients were given PEX and immunosuppressive therapy in the form of corticosteroid treatment. Other immunosuppressive treatments, such as rituximab, were permitted but not required*
• Patients were then randomized to receive CABLIVI^® (n=72) or placebo (n=73) for the duration of daily PEX and 30 days thereafter
• Patients could receive extended treatment for up to 28 days if signs of underlying disease persisted, such as suppressed ADAMTS13 activity levels
• Primary endpoint: Time to platelet count normalization^†
• Secondary endpoint: Composite of aTTP/iTTP-related events during study-drug period: aTTP/iTTP-related death, recurrence,^‡ ≥1 major TE event

Compared with PEX and immunosuppressive therapy alone, patients receiving the addition of CABLIVI achieved^2,3:

*2 patients in each group did not receive any immunosuppressive therapy.
^†Platelet count normalization was defined as platelet count ≥150,000/μL, with discontinuation of daily PEX within 5 days thereafter.
^‡Thrombocytopenia after initial recovery of platelet count (platelet count ≥150,000/μL) that required reinitiation of daily PEX was considered a recurrence. Recurrences were termed exacerbations if they occurred within 30 days of the last PEX and relapses if they occurred more than 30 days after the last PEX.

Study objective:

• To help assess whether CABLIVI decreases mortality and the optimal timing of CABLIVI initiation, a multi-institutional study was conducted

Study design:

• International, multicenter, independent, retrospective cohort study in which 1015 patients were treated primarily between 2018 and 2023 (98.7%) with daily PEX, immunosuppressive therapy with corticosteroids ± rituximab,^§ and CABLIVI (CABLIVI group), which was compared with historic controls treated with PEX and corticosteroids ± rituximab (control group, n=510)
• CABLIVI initiation was classified as early (within 3 days; 76% of cases) or delayed (≥4 days from first PEX)
• Featured participation of expert clinicians and biologists from 12 university hospitals worldwide
• 2 cohorts of patients treated with CABLIVI and control patients were recruited on the basis of stringent inclusion criteria according to the updated definition of thrombotic thrombocytopenic purpura—ie, thrombotic microangiopathy with no associated condition and with severe ADAMTS13 deficiency

Study limitations:

• Due to the limitations of this study’s retrospective, multicenter, real-world analysis design, the findings represent associations and should not be interpreted as establishing causality
• The selection of patients involved only experienced teams, as reflected by the low death rate in both therapeutic groups; hence, our results may only apply to participating centers
• The use of rituximab was variable between teams and its use was more systematic in the CABLIVI group, reflecting a wider adoption of rituximab in the more-recent patients; however, virtually all patients in the CABLIVI group achieved clinical response within 8 days, compared with the previous 2 to 3 weeks onset of ADAMTS13 response observed with rituximab

Dosing administration in the phase 3 HERCULES clinical trial:

• CABLIVI was administered as a single 11-mg IV bolus injection prior to PEX,^∥ followed by a daily 11-mg SC injection for the duration of PEX, and continued for 30 days thereafter¹

^§Rituximab is not approved by the US Food and Drug Administration (FDA) for the use under investigation. Sanofi does not promote or encourage the use of its products outside their FDA approved labeling.^4 
∥In combination with PEX and immunosuppressive therapy.

Comparable clinical presentation at diagnosis: CABLIVI vs control¹

^||French diagnostic score of 2: platelet count <30×10³/mm³ and serum creatinine <200 μmol/L (2.27 mg/dL); score of 1: platelet count <30×10³/mm³ or serum creatinine <200 μmol/L (2.27 mg/dL); score of 0: platelet count ≥30×10³/mm³ and serum creatinine ≥200 μmol/L (2.27 mg/dL).
^¶Patients at high risk of early death from aTTP were defined by French severity score ≥3 (cerebral involvement: yes=1/no=0; LDH: >10×ULN=1/≤10×ULN=0; age: >60 years=2/>40 and ≤60 years=1/≤40 years=0).