Integrated efficacy end points for the overall ITT population
| Efficacy end points . | Caplacizumab (n = 108) . | Placebo (n = 112) . | P . |
|---|---|---|---|
| Proportion of participants with ≥1 of the events below while receiving blinded study drug treatment | 14 (13.0) | 53 (47.3) | <.001 |
| TTP-related death | 0 (0.0) | 4 (3.6) | |
| Major thromboembolic event* | 8 (7.4) | 14 (12.5) | |
| TTP exacerbation | 6 (5.6) | 39 (34.8) | |
| TTP recurrences† | |||
| TTP exacerbation during blinded treatment period | 6 (5.6) | 39 (34.8) | <.001 |
| TTP relapses during treatment-free follow-up period | 14 (13.0) | 0 (0.0) | n/s |
| TTP exacerbation or relapse during overall study | 19 (17.6) | 39 (34.8) | .0040 |
| Refractory to treatment‡ | 0 (0.0) | 8 (7.1) | <.01 |
| Mortality rate | |||
| During the blinded treatment periods | 0 (0.0) | 4 (3.6) | .0477 |
| During the overall study period | 1 (0.9)§ | 5 (4.5)§ | n/s |
| Efficacy end points . | Caplacizumab (n = 108) . | Placebo (n = 112) . | P . |
|---|---|---|---|
| Proportion of participants with ≥1 of the events below while receiving blinded study drug treatment | 14 (13.0) | 53 (47.3) | <.001 |
| TTP-related death | 0 (0.0) | 4 (3.6) | |
| Major thromboembolic event* | 8 (7.4) | 14 (12.5) | |
| TTP exacerbation | 6 (5.6) | 39 (34.8) | |
| TTP recurrences† | |||
| TTP exacerbation during blinded treatment period | 6 (5.6) | 39 (34.8) | <.001 |
| TTP relapses during treatment-free follow-up period | 14 (13.0) | 0 (0.0) | n/s |
| TTP exacerbation or relapse during overall study | 19 (17.6) | 39 (34.8) | .0040 |
| Refractory to treatment‡ | 0 (0.0) | 8 (7.1) | <.01 |
| Mortality rate | |||
| During the blinded treatment periods | 0 (0.0) | 4 (3.6) | .0477 |
| During the overall study period | 1 (0.9)§ | 5 (4.5)§ | n/s |
Data are presented as n (%).
ITT, intent to treat; n/s, not statistically significant (P ≥ .05).
Based on standardized MedDRA (Medical Dictionary for Regulatory Activities) queries (Standardized MedDRA Query) in the TITAN trial (post hoc); confirmed after adjudication in the HERCULES trial.
Recurrence was defined as a new drop in platelet count after initial platelet count normalization, necessitating re-initiation of TPE. Exacerbation is a recurrence within 30 days after the end of daily TPE. Relapse is a recurrence occurring more than 30 days after the end of daily TPE.
Defined as a lack of sustained platelet count increment or platelet counts <50 × 109/L throughout the assessment period and persistently increased lactate dehydrogenase (>1.5 × upper limit of normal) despite 5 TPEs and steroid treatment.11
In the TITAN trial, 1 participant in the placebo group died 2 days after study drug treatment was permanently discontinued by physician decision and was therefore counted as a death during the follow-up period, despite dying from severe refractory disease in the acute setting. In the HERCULES trial, 1 participant in the caplacizumab group died in the follow-up period after completing treatment and reaching complete remission. Both participants had a confirmed TTP diagnosis (ADAMTS13 <10%).