Ireland-based Jazz Pharmaceuticals has begun patient enrolment in a Phase III clinical trial of defitelio (defibrotide sodium) against best supportive care (BSC) to address hepatic veno-occlusive disease (VOD) in adult and pediatric patients undergoing hematopoietic stem-cell transplant (HSCT).
Defitelio is an anti-thrombotic, thrombolytic and fibrinolytic polydeoxyribonucleotide, which increases the hydrolysis of fibrin clots by boosting the enzymatic activity of plasmin and minimising expression of adhesion molecules on endothelial cells by releasing prostaglandin 12.
It has been developed by Jazz Pharmaceuticals to treat VOD, also known as sinusoidal obstruction syndrome.
The Phase III trial will be conducted as a randomised, open-label, multi-centre trial to compare efficacy of defibrotide against BSC to prevent hepatic VOD.
The trial will be designed to allow analysis with pre-defined stopping points after experiencing an early success or failure, as well as accommodate more enrolment to preserve the statistical power of the trial.
The trial will enrol about 400 adult and pediatric patients undergoing HSCT who are at high risk or very high risk of developing VOD.
Jazz Pharmaceuticals chief medical officer and research and development global head Karen Smith said: "The initiation of this trial is another step forward in Jazz's development programme for defibrotide as a treatment option for patients who are at high risk or very high risk of developing this life-threatening condition.
"If the data from this trial is positive, it may be used to pursue regulatory approval of a label expansion for defibrotide in both the US and EU to include the prevention of hepatic VOD in high-risk patients following HSCT."
The patients will be randomised to receive defibrotide prophylaxis from the day prior to the day of the conditioning regimen for a recommended minimum of 21 days and ending within 30 days of post-HSCT.
The study is primarily focused on determining VOD-free survival after completing 30 days of post-HSCT.
Image: Picture of medicines. Photo: courtesy of Marcin Wysmulek.