- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02130817
Belatacept in Kidney Transplantation of Moderately Sensitized Patients (BelatPilot)
Belatacept for the Management of Moderately Sensitized Patients at Risk for Delayed Graft Function (DGF)
Study Overview
Status
Detailed Description
Study Type
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Wisconsin
-
Madison, Wisconsin, United States, 53792
- University of Wiscsonsin Hospital and Clinics
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female subjects 18-70 years of age
- Patient who is receiving an expanded criteria donor (ECD) or deceased cardiac donor (DCD) kidney
- Have immunodominant donor specific antibodies (DSA) 1,000 - 4,000 mean fluorescent intensity (MFI) by single bead Luminex bioassay
- Subjects must be capable of understanding the investigational nature and risks of the study and must sign a statement of informed consent
- Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion and be willing to use contraceptives for the duration of the study and for 8 weeks after the last dose of study drug Women of Child-Bearing Potential (WOCBP) includes
- Women who have experienced menarche and who have not undergone successful surgical sterilization or who are not post-menopausal
- Women using oral contraceptives, other hormonal contraceptives, or mechanical products such as intrauterine devices or barrier methods
- Women who are practicing abstinence
- Women who have a partner who is sterile (eg, due to vasectomy).
- Women must not be breast-feeding
- Male subjects must agree to use an acceptable method for contraception for the duration of the study
- Patient must have known positive Epstein-Barr virus (EBV) serostatus
Exclusion Criteria:
- Patient has previously received an organ transplant other than a kidney.
- Patient is receiving an human leukocyte antigen (HLA) identical living donor transplant
- Patient who is a recipient of a multiple organ transplant
- Patient with a positive T or B cell crossmatch
- Patient with a donor specific antibody (DSA) as deemed by the local PI to be associated with significant risk of rejection
- Patient has received an ABO incompatible donor kidney
- Recipients will be receiving a dual or en bloc kidney transplant
- Donor anticipated cold ischemia is > 30hours
- Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive. HCV seropositive patients with a negative HCV viral load testing may be included.
- Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV)
- Seronegative or unknown EBV serostatus
- Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives
- Patients with tuberculosis who have not been treated for latent infection.
- Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
- Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
- Patients with thrombocytopenia (PLT <75,000/mm3), and/or leucopoenia (WBC < 2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.
- Patient is taking or has been taking an investigational drug in the 30 days prior to transplant
- Patient who has undergone desensitization therapy within 6 months prior to transplant
- Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil, alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids
- Patient is receiving chronic steroid therapy at the time of transplant
- Patients with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years
- Patients with > Grade 2 peripheral neuropathy within 14 days before enrollment
- Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiography evidence of acute ischemia or active conduction system abnormalities.
- Female subject is pregnant or breast-feeding
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
- Prisoners or subjects who are involuntarily incarcerated
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Belatacept
Belatacept (nujolix): Tacrolimus withdrawal Standard of care(SOC) treatment: Plasmapheresis/Intravenous Immunoglobulin G (IVIG) therapy Thymoglobulin will be administered to a total cumulative dose of 4.5-6 mg/kg starting in the operating room. Maintenance immunosuppression: Myfortic: Patients will receive 720mg bid of Myfortic throughout the study, starting day 1 after surgery. Steroids: Patients will receive Dexamethasone IV on the day of surgery (Day 0) with tapered doses through Day 4 followed by prednisone tapered to 10mg/d by day 30. |
Belatacept will be added to the standard of care regimen and will be given at days 0,5, weeks 2, 4, 8 and 12 (10 mg/kg) and every 4 weeks (5 mg/kg) for one year.
Other Names:
Tacrolimus dosing will begin on Days 1 through 5 post transplant at up to 2 mg BID to achieve target trough levels of 9-11 ng/ml.
The dose will be tapered through the end of week 2 to achieve a trough level of 4 ng/ml which will be maintained for six weeks.
Tacrolimus will be withdrawn at the end of eight weeks post transplant.
Enrolled patients will start with standard of practice treatment including plasmapheresis and IVIG therapy twice after transplant, on days 2 and 4 and potentially once before transplant.
Plasmapheresis and albumin exchange for one volume of blood will be performed in the infusion center at the University of Wisconsin Hospital and Clinics (UWHC).
Each pheresis session will be completed by IVIG infusion.
While plasmapheresis will help with the removal of circulating Donor Specific Antibodies (DSA), IVIG therapy will provide immunomodulatory characteristics that include sterilizing immunity from infections, inhibiting and scavenging activated complement fragments, modifying cell-mediated immune responses, inducing regulatory T cells and importantly, inhibiting deleterious antibody production.
Thymoglobulin (ATG) Induction.
Thymoglobulin will be administered to a total cumulative dose of 4.5-6 mg/kg via a peripheral or central vein, starting in the operating room.
Other Names:
Patients will receive 720mg bid of Myfortic throughout the study, starting day 1 after surgery.
Patients will receive Dexamethasone IV on the day of surgery (Day 0) with tapered doses through Day 4 followed by prednisone tapered to 10mg/d by day 30.,
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Acute rejection
Time Frame: one year
|
Acute rejection rates are based on assessment of standard of care biopsy (protocol and indication) and standard Banff criteria.
|
one year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient and Graft Survival
Time Frame: One year
|
The number of subjects alive and with functioning grafts at one year.
|
One year
|
Incidence of infections
Time Frame: One year
|
Number of subjects in the study who have developed infections, including cytomegalovirus (CMV) and BK Virus, in the first year post-transplant
|
One year
|
Incidence of de novo donor specific antibody (DSA)
Time Frame: One year
|
Number of subjects who have developed donor specific antibodies at one year post transplant.
|
One year
|
Incidence of new onset diabetes
Time Frame: One year
|
Number of subjects in the study who have developed new onset diabetes since receiving the transplant
|
One year
|
Increase in estimated Glomerular Filtration Rate (eGFR)
Time Frame: One year
|
Number of subjects in the study whose eGFR has decreased to < 45 milliliters/ minute
|
One year
|
Incidence of malignancies
Time Frame: One year
|
Number of subjects in the study who have developed malignancies including post-transplant lymphoproliferative (PTLD) disorder
|
One year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Arjang Djamali, M.D., University of Wisconsin, Madison
Publications and helpful links
General Publications
- Trivedi HL, Terasaki PI, Feroz A, Everly MJ, Vanikar AV, Shankar V, Trivedi VB, Kaneku H, Idica AK, Modi PR, Khemchandani SI, Dave SD. Abrogation of anti-HLA antibodies via proteasome inhibition. Transplantation. 2009 May 27;87(10):1555-61. doi: 10.1097/TP.0b013e3181a4b91b.
- Jordan SC, Pescovitz MD. Presensitization: the problem and its management. Clin J Am Soc Nephrol. 2006 May;1(3):421-32. doi: 10.2215/CJN.01651105. Epub 2006 Apr 12.
- Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant. 2006 Feb;6(2):346-51. doi: 10.1111/j.1600-6143.2005.01178.x.
- Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.
- Montgomery RA, Zachary AA. Transplanting patients with a positive donor-specific crossmatch: a single center's perspective. Pediatr Transplant. 2004 Dec;8(6):535-42. doi: 10.1111/j.1399-3046.2004.00214.x.
- Magee CC, Felgueiras J, Tinckam K, Malek S, Mah H, Tullius S. Renal transplantation in patients with positive lymphocytotoxicity crossmatches: one center's experience. Transplantation. 2008 Jul 15;86(1):96-103. doi: 10.1097/TP.0b013e318176ae2c.
- Thielke JJ, West-Thielke PM, Herren HL, Bareato U, Ommert T, Vidanovic V, Campbell-Lee SA, Tzvetanov IG, Sankary HN, Kaplan B, Benedetti E, Oberholzer J. Living donor kidney transplantation across positive crossmatch: the University of Illinois at Chicago experience. Transplantation. 2009 Jan 27;87(2):268-73. doi: 10.1097/TP.0b013e3181919a16.
- Jordan SC, Toyoda M, Vo AA. Intravenous immunoglobulin a natural regulator of immunity and inflammation. Transplantation. 2009 Jul 15;88(1):1-6. doi: 10.1097/TP.0b013e3181a9e89a.
- Investigator Brochure. Belatacept (BMS-2224818), Version 13. Bristol-Myers Squibb Research and Development Department. 15 December 2010.
- U.S. Prescribing information for Nulojix® (belatacept), Revised 06/2011. Bristol-Myers Squibb.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Kidney Diseases
- Urologic Diseases
- Renal Insufficiency
- Renal Insufficiency, Chronic
- Kidney Failure, Chronic
- Delayed Graft Function
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Immune Checkpoint Inhibitors
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Dexamethasone
- Immunoglobulins
- Immunoglobulins, Intravenous
- Prednisone
- Tacrolimus
- gamma-Globulins
- Rho(D) Immune Globulin
- Mycophenolic Acid
- Abatacept
- Thymoglobulin
- Antilymphocyte Serum
- Immunoglobulin G
Other Study ID Numbers
- Should be 2013-0672
- IM103-327 (Other Identifier: Study Team)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on End Stage Renal Disease
-
Outset MedicalCompletedAcute Kidney Injury | End Stage Renal Disease (ESRD) | End Stage Renal Disease on DialysisUnited States
-
University of Illinois at ChicagoWithdrawnObesity | End-Stage Renal Disease | Renal Disease, End-Stage | Renal Failure, End-StageUnited States
-
Bioconnect Systems, IncCompletedEnd-stage Renal Disease | End-stage Kidney DiseaseUnited States
-
Iperboreal Pharma SrlWithdrawnEnd-Stage Renal Disease
-
Cubist Pharmaceuticals LLCCompleted
-
Medical University of GrazWithdrawnEnd-stage Renal DiseaseAustria
-
Janssen Research & Development, LLCBayerCompleted
-
Chulalongkorn UniversityCompletedEnd-stage Renal DiseaseThailand
-
University of KansasCompletedEnd-Stage Renal Disease
-
Eisai Co., Ltd.CompletedEnd-Stage Renal DiseaseJapan
Clinical Trials on Belatacept
-
Bristol-Myers SquibbCompletedRenal TransplantationUnited States
-
Guizhou Provincial People's HospitalActive, not recruiting
-
Bristol-Myers SquibbCompletedKidney Transplantation | Chronic Kidney FailureUnited States, Argentina, Australia, Germany, Italy, South Africa, Spain, Brazil, Mexico, Belgium, France, Hungary, Switzerland, India, Canada, Austria, Czech Republic, Poland, Israel, Sweden, Turkey
-
Methodist Health SystemActive, not recruitingUse of Belatacept in Kidney Transplant PatientsUnited States
-
Bristol-Myers SquibbCompletedRenal TransplantationUnited States, Argentina, Germany, Italy, Chile, Spain, Brazil, Sweden, Belgium, France, Hungary, Australia, South Africa, Austria, Canada, United Kingdom, Poland, Czechia, Norway
-
Bristol-Myers SquibbCompletedHealthy VolunteersUnited States
-
Bristol-Myers SquibbCompletedRheumatoid ArthritisUnited States, Netherlands, Belgium, Canada, Germany, France, Ireland, Switzerland, United Kingdom
-
Bristol-Myers SquibbTerminatedImmunosuppression in Solid Organ TransplantFrance, Germany, Italy, United States, Austria, Canada, Spain, Argentina, Brazil
-
University of MarylandBristol-Myers SquibbCompletedEnd-Stage Renal DiseaseUnited States
-
Ain Shams UniversityRecruiting