Belatacept to Prevent Organ Rejection in Kidney Transplant Patients (BESTT)
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| ClinicalTrials.gov Identifier: NCT00346151 |
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Recruitment Status :
Terminated
(Stopping rule-acute rejection threshold-was met based on local biopsy results)
First Posted : June 29, 2006
Results First Posted : November 6, 2011
Last Update Posted : April 21, 2017
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Renal Transplant | Drug: Belatacept Drug: Sirolimus Drug: Anti-thymocyte globulin Drug: methylprednisolone | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 5 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | The Safety and Efficacy of Belatacept, Antithymocyte Globulin, and Sirolimus in Recipients of Non-HLA-identical Living-donor Renal Transplants (ITN023ST) |
| Study Start Date : | December 2006 |
| Actual Primary Completion Date : | February 2010 |
| Actual Study Completion Date : | February 2010 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Belatacept
Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus.
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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
Other Names:
Drug: 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
Other Names:
Drug: 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.
Other Names:
Drug: 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
Other Names:
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- Acute Rejection at 6-Months [ Time Frame: 6 months post-transplant ]
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
- Participant Survival at 12 Months Post-Transplant [ Time Frame: 12 months post-transplant ]
- Acute Rejection at 12-Months [ Time Frame: 12 months post-transplant ]
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
- Tolerance Induction [ Time Frame: 48 months ]Time from transplantation to initiation of sirolimus withdrawal.
- Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks [ Time Frame: 24 weeks post-transplant ]
GFR utilizing clearance of iothalamate.
GFR is an index of level of kidney function. A higher value means better kidney function.
- Graft Survival at 12 Months Post-transplant [ Time Frame: 12 months post-transplant ]
- Time From Transplant to Acute Rejection [ Time Frame: Transplantation until rejection occurs (participants followed up to four years post-transplantation) ]
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
- Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ]
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
- Proportion of Participants With Post-transplant Infections [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ]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)
- Proportion of Participants With Wound Complications [ Time Frame: Start of study to end of study ]
- Proportion of Participants With Malignancies [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ]
- Proportion of Participants With a Sirolimus Associated Adverse Event [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ]
- Proportion of Participants With Chronic Allograft Nephropathy [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ]
- Proportion of Participants With Delayed Graft Function [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ]
- Proportion of Participants With Post-transplant Diabetes Mellitus [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ]
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00346151
| United States, California | |
| University of California, San Francisco | |
| San Francisco, California, United States, 94143 | |
| United States, Georgia | |
| Emory University | |
| Atlanta, Georgia, United States, 30322 | |
| Principal Investigator: | Flavio Vincenti, MD | University of California, San Francisco | |
| Principal Investigator: | Christian Larsen, MD | Emory University |
Study Data/Documents: Individual Participant Data Set
ImmPort study identifier is SDY674
ImmPort study identifier is SDY674. The study protocol is available in the Design tab section.
ImmPort study identifier is SDY674
TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available.
TrialShare is a clinical trials research portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available.
Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00346151 |
| Other Study ID Numbers: |
DAIT ITN023ST |
| First Posted: | June 29, 2006 Key Record Dates |
| Results First Posted: | November 6, 2011 |
| Last Update Posted: | April 21, 2017 |
| Last Verified: | March 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Data access is provided to the public in Participant level data and additional relevant materials are available to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available. |
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renal transplantation kidney transplantation renal allograft recipient |
anti-rejection drugs immunosuppression protocol immunosuppression withdrawal |
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Sirolimus Methylprednisolone Abatacept Thymoglobulin Antilymphocyte Serum Immunoglobulins Glucocorticoids Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antineoplastic Agents Antifungal Agents Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Molecular Mechanisms of Pharmacological Action Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Neuroprotective Agents Protective Agents Immune Checkpoint Inhibitors Antineoplastic Agents, Immunological Antirheumatic Agents |