Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients

• ClinicalTrials.gov Identifier: NCT02851407
• Recruitment Status: Completed
• First Posted: August 1, 2016
• Last Update Posted: October 22, 2020
• Sponsor: Jazz Pharmaceuticals
• Information provided by (Responsible Party): Jazz Pharmaceuticals

Tracking Information

• First Submitted Date: July 27, 2016
• First Posted Date: August 1, 2016
• Last Update Posted Date: October 22, 2020
• Actual Study Start Date: September 2016
• Actual Primary Completion Date: October 13, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2016)

Veno-Occlusive Disease (VOD)-Free Survival at Day 30 Post-Hemotopoietic Stem Cell Transplant (HSCT) [ Time Frame: 30 Days Post-Transplant ]

Comparison of efficacy of defibrotide vs Best Supportive Care (BSC) for the prevention of VOD

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 28, 2016)

Veno-Occlusive Disease (VOD)-Free Survival at Day 100 Post-Hemotopoietic Stem Cell Transplant (HSCT) [ Time Frame: 100 Days Post-Transplant ]

Comparison of efficacy of defibrotide vs Best Supportive Care (BSC) for the prevention of VOD

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients
• Official Title: A Phase 3, Randomized, Adaptive Study Comparing the Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant
• Brief Summary: This study is to compare the efficacy and safety of defibrotide prophylaxis in addition to best supportive care versus best supportive care alone in the prevention of hepatic veno- occlusive disease (VOD) in adult and pediatric patients undergoing hematopoietic stem cell transplant who are at high risk or very high risk of developing VOD.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Veno-occlusive Disease

Intervention

• Drug: Defibrotide
• Other: Best Supportive Care

Study Arms

• Experimental: Defibrotide
  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
  Intervention: Drug: Defibrotide
• Best Supportive Care
  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
  Intervention: Other: Best Supportive Care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 21, 2020): 373
• Original Estimated Enrollment (submitted: July 28, 2016): 400
• Actual Study Completion Date: October 13, 2020
• Actual Primary Completion Date: October 13, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 very high risk of developing veno-occlusive disease (VOD).
3. Female patients (and female partners of male patients) of childbearing potential who are sexually active must agree to use a highly effective method of contraception with their partners during exposure to defibrotide and for 1 week after the last dose of defibrotide.
4. Adult patients must be able to understand and sign a written informed consent. For minor patients, the parent/legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria:

1. Patient has hemodynamic instability within 24 hours before the start of study treatment.
2. Patient has acute bleeding that is clinically significant within 24 hours before the start of study treatment.
3. Patient used any medication that increases the risk of bleeding within 24 hours before the start of study treatment.
4. Patient is using or plans to use an investigational agent for the prevention or treatment of VOD.
5. Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
6. Patient or parent/legal guardian or representative has a psychiatric illness that would prevent the patient or parent/legal guardian or representative from giving informed consent and/or assent.
7. Patient has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study.
8. Patient is pregnant or lactating and does not agree to stop breastfeeding.
9. Patient has a known history of hypersensitivity to defibrotide or any of the excipients.
10. Patient or parent/legal guardian or representative lacks the full mental capacity to understand and sign a written informed consent.
11. Patient is receiving or plans to receive other investigational therapy during study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Australia, Belgium, Canada, France, Israel, Italy, Japan, Korea, Republic of, New Zealand, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT02851407
• Other Study ID Numbers: 15-007
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Jazz Pharmaceuticals
• Study Sponsor: Jazz Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Jazz Pharmaceuticals; Jazz Pharmaceuticals

• PRS Account: Jazz Pharmaceuticals
• Verification Date: October 2020