Belatacept to Prevent Organ Rejection in Kidney Transplant Patients

Renal Transplant Clinical Trial

— BESTT  

Official title:

The Safety and Efficacy of Belatacept, Antithymocyte Globulin, and Sirolimus in Recipients of Non-HLA-identical Living-donor Renal Transplants (ITN023ST)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00346151
• Other study ID #: DAIT ITN023ST
• Status: Terminated
• Phase: Phase 2
• First received: June 27, 2006
• Last updated: December 30, 2014
• Start date: December 2006
• Est. completion date: February 2010

Study information

• Verified date: December 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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rejection of a first-time, non-human leukocyte antigen (HLA) identical renal transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplant

Intervention

Drug:
• Belatacept
10 mg/kg given intravenously (IV) on transplant (day 1), day 5, and at weeks 2, 4, 8 and 12, then 5 mg/kg IV every 4 weeks
• Sirolimus
4 mg/day (oral tablet) at transplant (day 1), then dose adjusted to maintain serum trough level of 8-12 ng/mL for at least 1 year
• Anti-thymocyte globulin
1.5 mg/kg given IV daily on days 1 through 4. Subjects are premedicated with glucocorticoids, acetaminophen 650 mg by mouth, and diphenhydramine 25- 50 mg by mouth prior to each dose.
• methylprednisolone
500 mg given IV at transplant (day 1), then given 250 mg IV on day 2 and given 0.5 mg/kg IV or prednisone 0.5 mg/kg given by mouth on days 3 and 4

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Rejection at 6-Months	Cumulative incidence of acute rejection[1] at 6 months post-transplant based on local pathology biopsy reads; Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]; Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999	6 months post-transplant	Yes
Secondary	Participant Survival at 12 Months Post-Transplant		12 months post-transplant	Yes
Secondary	Acute Rejection at 12-Months	Incidence of acute rejection[1] at 12 months post-transplant; Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]; Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999	12 months post-transplant	Yes
Secondary	Tolerance Induction	Time from transplantation to initiation of sirolimus withdrawal.	48 months	No
Secondary	Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks	GFR utilizing clearance of iothalamate.; GFR is an index of level of kidney function. A higher value means better kidney function.	24 weeks post-transplant	No
Secondary	Graft Survival at 12 Months Post-transplant		12 months post-transplant	Yes
Secondary	Time From Transplant to Acute Rejection	Time (days) from transplant to occurrence of acute rejection[1]; Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]; Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999	Transplantation until rejection occurs (participants followed up to four years post-transplantation)	Yes
Secondary	Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection	Proportion of participants who experienced acute rejection[1] requiring antilymphocyte therapy; Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]; Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999	Participants followed from transplantation until completion of study (up to four years post-transplantation)	Yes
Secondary	Proportion of Participants With Post-transplant Infections	Proportion of participants who experienced infections post-transplant. Participants were checked for any type of opportunistic infection at all study visits post-transplantation (up to 4 years post-transplantation)	Participants followed from transplantation until completion of study (up to four years post-transplantation)	Yes
Secondary	Proportion of Participants With Wound Complications		Start of study to end of study	Yes
Secondary	Proportion of Participants With Malignancies		Participants followed from transplantation until completion of study (up to four years post-transplantation)	Yes
Secondary	Proportion of Participants With a Sirolimus Associated Adverse Event		Participants followed from transplantation until completion of study (up to four years post-transplantation)	Yes
Secondary	Proportion of Participants With Chronic Allograft Nephropathy		Participants followed from transplantation until completion of study (up to four years post-transplantation)	Yes
Secondary	Proportion of Participants With Delayed Graft Function		Participants followed from transplantation until completion of study (up to four years post-transplantation)	Yes
Secondary	Proportion of Participants With Post-transplant Diabetes Mellitus		Participants followed from transplantation until completion of study (up to four years post-transplantation)	Yes

External Links

•   Immune Tolerance Network (ITN) Website
•   ITN TrialShare: open public access to participant-level data available for this trial