Clinical trial NCT00346151: Belatacept to Prevent Organ Rejection in Kidney Transplant Patients
Official title: The Safety and Efficacy of Belatacept, Antithymocyte Globulin, and Sirolimus in Recipients of Non-HLA-identical Living-donor Renal Transplants (ITN023ST)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Renal Transplant
Keywords: renal transplantation
kidney transplantation
renal allograft recipient
anti-rejection drugs
immunosuppression protocol
immunosuppression withdrawal
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2006-06-29
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Belatacept is an experimental medication shown in clinical trials to have immune system suppression properties in people who have had renal (e.g., kidney) transplants. This study will determine whether a combination of anti-rejection drugs, including belatacept, can prevent the rejection of a first-time, non-human leukocyte antigen (HLA) identical renal transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.

Detailed description: Drugs that suppress the immune system have contributed to increased success of transplantation; however, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives. These drugs make patients more susceptible to infection and certain kinds of cancer. Belatacept is an experimental medication that specifically targets immune reactions against transplanted organs and has been shown to be effective in preventing kidney transplant rejection in previous clinical trials. Both thymoglobulin, an antibody, and sirolimus, an anti-rejection drug, prevent rejection by lowering the response of the immune system to the transplanted organ. This study will evaluate whether belatacept, along with thymoglobulin and sirolimus, is safe in kidney transplant patients. The study will also evaluate this regimen's potential to allow tapering and eventual discontinuation of all immunosuppressive drugs.

This study will last up to 4 years. At the time of transplant, participants will begin an immunosuppressive treatment regimen consisting of thymoglobulin, sirolimus, and belatacept. Participants will receive infusions of thymoglobulin on days 1 through 4, and a combination of oral sirolimus (daily) and belatacept infusions at day 5, then weeks 2, 4, 8, and monthly for at least 2 years. Dose reduction of belatacept will occur at 12 weeks post-transplant. At Year 2, eligible participants may choose to begin drug withdrawal or continue study therapy through the end of the study. Study visits will occur weekly for the first two months, then monthly. These visits will include belatacept treatment, general medical assessments, blood and urine collection, and other assessments to determine overall health of the recipient's immune system and kidney transplant and to better understand the way the immune system works in the acceptance or rejection of organ transplants.

\*\*\* IMPORTANT NOTICE: \*\*\* The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.

Eligibility criteria: Inclusion Criteria:

* Receiving first renal (e.g., kidney) transplant
* Transplant is from a non-HLA-identical living donor
* Willing to use acceptable forms of contraception

Exclusion Criteria:

* Positive for anti-human globulin (AHG) or T-cell cross-match with the donor
* Receiving multiple-organ transplant
* History of cancer within the 5 years prior to study entry. Patients who have certain nonmelanoma skin cancers are not excluded
* Human immunodeficiency virus (HIV) infected
* Hepatitis B (HBV) or C (HCV) virus infected
* Other active infections
* Active tuberculosis (TB) infection within the 3 years prior to study entry
* Pregnancy or breastfeeding

Primary outcomes:
measure: Acute Rejection at 6-Months
timeFrame: 6 months post-transplant
Secondary outcomes:
measure: Participant Survival at 12 Months Post-Transplant
timeFrame: 12 months post-transplant
measure: Acute Rejection at 12-Months
timeFrame: 12 months post-transplant
measure: Tolerance Induction
timeFrame: 48 months
measure: Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks
timeFrame: 24 weeks post-transplant
measure: Graft Survival at 12 Months Post-transplant
timeFrame: 12 months post-transplant
measure: Time From Transplant to Acute Rejection
timeFrame: Transplantation until rejection occurs (participants followed up to four years post-transplantation)
measure: Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection
timeFrame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
measure: Proportion of Participants With Post-transplant Infections
timeFrame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
measure: Proportion of Participants With Wound Complications
timeFrame: Start of study to end of study
measure: Proportion of Participants With Malignancies
timeFrame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
measure: Proportion of Participants With a Sirolimus Associated Adverse Event
timeFrame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
measure: Proportion of Participants With Chronic Allograft Nephropathy
timeFrame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
measure: Proportion of Participants With Delayed Graft Function
timeFrame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
measure: Proportion of Participants With Post-transplant Diabetes Mellitus
timeFrame: Participants followed from transplantation until completion of study (up to four years post-transplantation)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: University of California, San Francisco
name: Flavio Vincenti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Christian Larsen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G, Lang P, Grinyo J, Halloran PF, Solez K, Hagerty D, Levy E, Zhou W, Natarajan K, Charpentier B; Belatacept Study Group. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005 Aug 25;353(8):770-81. doi: 10.1056/NEJMoa050085.