Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Defibrotide · 6 trials · 9 indications
VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria adjudicated by a blinded independent EPAC. An event is defined as a VOD diagnosis (as assessed by the EPAC) or death, whichever, is earlier, up to and including Day +30 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +30 post-HSCT.
The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.
The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.
Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the International Bone Marrow Transplant Registry (IBMTR) Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Major hemorrhagic complications will be based on the International Society on Thrombosis and Haemostasis Bleeding scale. 1. Fatal Bleeding, and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or 3. Bleeding associated with a decline in hemoglobin level of \> 2.0 g/dl, leading to transfusion of two or more units of whole blood or red cells. 4. In addition, symptomatic alveolar hemorrhage, macroscopic hematuria, uncontrolled menorrhagia or epistaxis or bleeding from any wound site would also be considered a major hemorrhagic event.
| Arm | Type | Description |
|---|---|---|
| Defibrotide | EXPERIMENTAL | Defibrotide is administered intravenously at a dose of 25 mg/kg/day in addition to best supportive care on the day before the first day of the conditioning regimen and will continue (for those patients without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post HSCT |
| Best Supportive Care | OTHER | Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and patient need, is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner, or diagnosis of VOD, if applicable |
| Historical Control | NO_INTERVENTION | Historical control group |
| Arm A Lower dose | EXPERIMENTAL | This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide. \- Arm I: On days 2-14, patients receive a lower dose of defibrotide IV over 2 hours every 6 hours. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity |
| Arm B Higher Dose | EXPERIMENTAL | This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide. \- Arm II: On days 2-14, patients receive a higher dose of defibrotide IV over 2 hours every 6 hours. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity |
| Defibrotide Prophylaxis | EXPERIMENTAL | Standard of Care Immunoprophylaxis + Defibrotide |
| Standard of Care | ACTIVE_COMPARATOR | Standard of Care Immunoprophylaxis Alone |
| Name | Type | Description |
|---|---|---|
| Defibrotide | DRUG | - |
| Best Supportive Care | OTHER | - |
| Standard of Care | DRUG | Administered according to local institutional guidelines, physician preference, and patient need. |
Inclusion Criteria: 1. Patient must be above the age of 1 month as of the start date of study treatment. 2. Patient must be scheduled to undergo allogeneic hematopoietic stem cell transplant (HSCT) (adults or pediatric patients) or autologous HSCT (pediatric patients only) and be at high risk or ve...
Defibrotide is used for hepatic veno-occlusive disease, severe hepatic veno-occlusive disease, veno-occlusive disease, COVID, and graft-versus-host disease. It is being developed by Jazz Pharmaceuticals plc (JAZZ) as a small molecule for infectious disease.
Defibrotide is a small molecule that does not have a specific molecular target or target class identified. Its mechanism of action is not described in the available information.
Defibrotide is being developed by Jazz Pharmaceuticals plc, which is listed on the stock exchange under the ticker JAZZ. The company is conducting clinical trials for this drug in various indications.
Defibrotide is in Phase 1 clinical development. It has completed two trials, including a Phase 2 and a Phase 3 study, but the current phase is Phase 1. It is investigational and not yet approved.
Defibrotide has completed four clinical trials: NCT00003966 (Phase 2, veno-occlusive disease), NCT00358501 (Phase 3, severe hepatic veno-occlusive disease), NCT00628498 (Phase 3, hepatic veno-occlusive disease), and NCT04530604 (Phase 1, COVID-19 ARDS).
Defibrotide is not known by any alternative names in the available information. It is referred to solely as Defibrotide in clinical trials and development.