TITAN trial

Background

Phase II TITAN, N=75, acquired TTP requiring plasma exchange. Randomized to caplacizumab vs placebo, both added to plasma exchange and immunosuppression.

Interventions and follow up

Arm A: caplacizumab 10 mg IV bolus day 1 before first plasma exchange, then 10 mg SQ daily from day 1 until 30 days after the last day of plasma exchange.
Arm B: standard of care + placebo (dosed identically to caplacizumab).
Primary endpoint: time to platelet normalization (≥150,000/mm3 confirmed ×2, 48 h apart).

Results

Median time to platelet normalization: 3.0d vs 4.9d, event rate ratio 2.2 (1.28-3.78), P=.005
Complete remission (caplacizumab vs placebo): 81% vs 46%
Relapse during treatment: 22% vs 0
Relapse at 12 mo: 31% vs 46%
Plasma exchange, initial period: 5.9d vs 7.9d; 19.9L vs 28.3L
Plasma exchange, overall period: 7.7d vs 11.7d; 25.8L vs 41.8L

Adverse events

Bleeding (A vs B): 54% vs 38%
Immune-related events: 49% vs 32%
Serious adverse events: 37% vs 32%

Conclusions

Added to plasma exchange and immunosuppression, caplacizumab shortened time to platelet normalization and reduced relapse during treatment. Bleeding is the principal complication.

Key Limitations

Phase II, modest N; surrogate primary endpoint (platelet normalization); relapses clustered after drug discontinuation, suggesting unresolved autoimmune activity; not powered for mortality.

Clinical Context

Anti-vWF nanobody; results confirmed in the phase III HERCULES trial, leading to FDA/EMA approval of caplacizumab for acquired TTP alongside plasma exchange and immunosuppression. ISTH guidance supports caplacizumab in the frontline triple-therapy regimen.

References