Budesonide for Liver Transplant Immune Suppression

NCT03304626 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2016-1488
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study that investigates the efficacy and safety of budesonide as an immune suppressing agent for liver transplant recipients in the early post-transplant period. The primary end-point is rates of acute cellular rejection within first 24 weeks post-liver transplant. Secondary end points include rates of new onset diabetes after transplant and safety of budesonide. The study is structured as a prospective clinical trial. After receiving 4 days of intravenous corticosteroids on liver transplant post-operative days 0 through 3, subjects will be started on standard immunosuppression plus enteric coated budesonide (study drug) in place of standard immune suppression plus prednisone (standard of care). Study drug will be tapered over 12 weeks in accordance with the existing standard of care immune suppression protocol. Subjects will be followed in outpatient transplant clinic for 24 weeks. The purpose of the study is to conduct a pilot study to generate rates and effect size that can be used in a subsequent equivalent trial. A total of 20 subjects will be enrolled to receive the standard immunosuppression plus budesonide and their outcomes will be compared to 20 controls receiving standard immunosuppression plus prednisone (standard of care). The use of controls is to generate rate and variability that can be compared with the rate obtained from patients that receive study drug by examining the 95% confidence band.

Conditions

Acute Cellular Graft Rejection; New Onset Diabetes After Transplant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Acute Cellular Rejection Between Study and Control Groups

  Acute Cellular Rejection of liver graft was determined by liver biopsy using Banff criteria. The decision to perform liver biopsy was as per treating physician based on patient's clinical course and blood chemisteries. Protocol bioopsies were not performed.

  Post-Transplant day 4 to week 24

Secondary Outcomes (3)

• Rate of New Onset Diabetes After Transplant

  Post-Transplant day 4 to week 24

• Number of Participants With Adrenal Suppression

  Post-Transplant week 12

• Number of Participants With Adverse Events

  Post-Transplant day 4 to week 24

Study Arms (2)

Study Group

EXPERIMENTAL

Budesonide EC 3 mg capsule. The dose will be as follows Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1

Drug: Budesonide 3Mg Capsule

Control Group

ACTIVE COMPARATOR

Standard of Care Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS

Drug: Standard of Care Prednisone

Interventions

Budesonide 3Mg Capsule DRUG

Budesonide capsule in place of prednisone (standard of care)

Also known as: Entocort EC

Study Group

Standard of Care Prednisone DRUG

Prednisone taper (Standard of Care)

Also known as: Prednisone

Control Group

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male subjects aged 21-75 years old
• Received a primary liver transplant within 4 days of enrollment

You may not qualify if:

• Received previous organ transplants
• Undergoing multiple organ transplants
• Recipients with advanced fibrosis in graft
• Treatment plan for subject includes receiving immunosuppressant therapy other than standard immune suppression (SIS) as per University of Cincinnati LT immune suppression protocol (UC-ISP).
• Inability to take enteral (orally or by tube feed) medications by day 4 post-transplant
• Subjects with diabetes mellitus prior to transplant (diabetes mellitus defined as use of hypoglycemic agents or HbA1c \> 6.4 prior to transplant)
• Subjects who have any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation.
• Subjects who have been exposed to an investigational therapy within 30 days prior to enrollment or 5 half-lives on the investigational product, whichever is greater.
• Subjects in which concomitant use of medications which are inhibitors of CYP3A4 (such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin) cannot be avoided during the study period.
• Pregnant females
• Diminished mental capacity to consent for the study as determined by attending on the record.

Sponsors & Collaborators

• University of Cincinnati: lead
• American College of Gastroenterology: collaborator

Study Sites (1)

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

MeSH Terms

Interventions

Budesonide; Prednisone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes

Results Point of Contact

• Title: Khurram Bari
• Organization: University of Cincinnati

khurram.bari@uc.edu

513-558-2898

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 20 subjects will receive open label Budesonide along with standard immune suppression and their outcomes will be compared to 20 matched controls receiving standard of care treatment including prednisone plus standard immune suppression

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 9, 2017
• Study Start: June 27, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: July 20, 2021
• Results First Posted: July 20, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)