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Stopping rule-acute rejection threshold-was met based on local biopsy results
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| Name | Class |
|---|---|
| Immune Tolerance Network (ITN) | NETWORK |
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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rejection of a first-time, non-human leukocyte antigen (HLA) identical renal transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Belatacept | Experimental | Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belatacept | Drug | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Acute Rejection at 6-Months | Cumulative incidence of acute rejection[1] at 6 months post-transplant based on local pathology biopsy reads
| 6 months post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Participant Survival at 12 Months Post-Transplant | 12 months post-transplant | |
| Acute Rejection at 12-Months | Incidence of acute rejection[1] at 12 months post-transplant
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Flavio Vincenti, MD | University of California, San Francisco | Principal Investigator |
| Christian Larsen, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94143 | United States | ||
| Emory University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16120857 | Background | 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. |
| Label | URL |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) website | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| SDY674 | Individual Participant Data Set | View IPD |
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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At a screening visit, participants underwent procedures to establish inclusion/exclusion criteria and sign the informed consent form.
Two centers in the United States enrolled five recipients of non-human leukocyte antigen (HLA)-identical living-donor-related renal transplants between January 2007 and January 2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | Belatacept | Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Immunosuppression Withdrawal | Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Acute Rejection at 6-Months | Cumulative incidence of acute rejection[1] at 6 months post-transplant based on local pathology biopsy reads
| Intent to Treat | Posted | Number | Participants | 6 months post-transplant |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Immunosuppression Withdrawal | Daclizumab, antithymocyte globulin, sirolimus, or belatacept dosing with the intention of immunosuppression withdrawal |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphocele | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
The trial was stopped early due to meeting an acute rejection threshold of three acute rejections based on local pathology reads in the first five participants enrolled.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research Program | DAIT/NIAID | 301-594-7669 | DAITClinicalTrialsGov@niaid.nih.gov |
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| ID | Term |
|---|---|
| D000069594 | Abatacept |
| D020123 | Sirolimus |
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| D008775 | Methylprednisolone |
| D005938 | Glucocorticoids |
| ID | Term |
|---|---|
| D018796 | Immunoconjugates |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D012712 | Serum Globulins |
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| Sirolimus | Drug | 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 | Drug | 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 | Drug | 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 |
|
|
| 12 months post-transplant |
| Tolerance Induction | Time from transplantation to initiation of sirolimus withdrawal. | 48 months |
| 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 |
| Graft Survival at 12 Months Post-transplant | 12 months post-transplant |
| Time From Transplant to Acute Rejection | Time (days) from transplant to occurrence of acute rejection[1]
| Transplantation until rejection occurs (participants followed up to four years post-transplantation) |
| Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection | Proportion of participants who experienced acute rejection[1] requiring antilymphocyte therapy
| Participants followed from transplantation until completion of study (up to four years post-transplantation) |
| 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) |
| Proportion of Participants With Wound Complications | Start of study to end of study |
| Proportion of Participants With Malignancies | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
| Proportion of Participants With a Sirolimus Associated Adverse Event | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
| Proportion of Participants With Chronic Allograft Nephropathy | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
| Proportion of Participants With Delayed Graft Function | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
| Proportion of Participants With Post-transplant Diabetes Mellitus | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| Division of Allergy, Immunology, and Transplantation (DAIT) website | View source |
| Immune Tolerance Network (ITN) website | View source |
ImmPort study identifier is SDY674 |
| SDY674 | Study Protocol | View IPD | ImmPort study identifier is SDY674. The study protocol is available in the Design tab section. |
| SDY674 | Study summary, -design, -synopsis,- medications, -demographics, -lab tests, -files | View IPD | ImmPort study identifier is SDY674 |
| ITN023ST | Individual Participant Data Set | View IPD | 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. |
| ITN023ST | Protocol synopsis, -data and reports, -specimens availability | View IPD | 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. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Secondary | Participant Survival at 12 Months Post-Transplant | Intent to Treat Sample participants not terminating prior to 12 months. | Posted | Number | Participants | 12 months post-transplant |
|
|
|
|
| Secondary | Acute Rejection at 12-Months | Incidence of acute rejection[1] at 12 months post-transplant
| Intent to Treat Sample | Posted | Number | Participants | 12 months post-transplant |
|
|
|
|
| Secondary | Tolerance Induction | Time from transplantation to initiation of sirolimus withdrawal. | Intent to treat sample that initiated sirolimus withdrawal | Posted | Number | Days | 48 months |
|
|
|
| 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. | Intent to Treat Sample | Posted | Mean | Standard Deviation | mL/min/1.73m^2 | 24 weeks post-transplant |
|
|
|
| Secondary | Graft Survival at 12 Months Post-transplant | Intent to treat sample participants not terminating prior to 12 months | Posted | Number | Participants | 12 months post-transplant |
|
|
|
|
| Secondary | Time From Transplant to Acute Rejection | Time (days) from transplant to occurrence of acute rejection[1]
| Intent to treat sample participants with rejection | Posted | Median | Full Range | Days | Transplantation until rejection occurs (participants followed up to four years post-transplantation) |
|
|
|
| Secondary | Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection | Proportion of participants who experienced acute rejection[1] requiring antilymphocyte therapy
| Intent to Treat Sample | Posted | Number | Participants | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
|
|
|
|
| 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) | Intent to Treat Sample | Posted | Number | Participants | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
|
|
|
|
| Secondary | Proportion of Participants With Wound Complications | Intent to Treat Sample | Posted | Number | Participants | Start of study to end of study |
|
|
|
|
| Secondary | Proportion of Participants With Malignancies | Intent to Treat Sample | Posted | Number | Participants | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
|
|
|
|
| Secondary | Proportion of Participants With a Sirolimus Associated Adverse Event | Intent to Treat Sample | Posted | Number | Participants | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
|
|
|
|
| Secondary | Proportion of Participants With Chronic Allograft Nephropathy | Intent to Treat Sample | Posted | Number | Participants | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
|
|
|
|
| Secondary | Proportion of Participants With Delayed Graft Function | Intent to Treat Sample | Posted | Number | Participants | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
|
|
|
|
| Secondary | Proportion of Participants With Post-transplant Diabetes Mellitus | Intent to Treat Sample | Posted | Number | Participants | Participants followed from transplantation until completion of study (up to four years post-transplantation) |
|
|
|
|
| 4 |
| 5 |
| 5 |
| 5 |
| Kidney transplant rejection | Immune system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Thrombocythaemia | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| Middle ear inflammation | Ear and labyrinth disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hyperparathyroidism | Endocrine disorders | MedDRA (11.1) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (11.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| Oedema | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (11.1) | Systematic Assessment |
|
| BK virus infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Cytomegalovirus viraemia | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Epstein-Barr viraemia | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Herpes virus infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Oral infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Graft dysfunction | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Incision site pain | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Medical device pain | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (11.1) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (11.1) | Systematic Assessment |
|
| Acidosis | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
|
| Renal disorder | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
|
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA (11.1) | Systematic Assessment |
|
| Scrotal oedema | Reproductive system and breast disorders | MedDRA (11.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
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| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D005916 | Globulins |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D007106 | Immune Sera |
| D007162 | Immunoproteins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |