Delayed Graft FunctionPhase 2NCT01837043
Early Conversion From CNI to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function
A Phase 2 study testing Belatacept and Calcineurin Inhibitor in people with Delayed Graft Function and Kidney Transplant, run by Nair, Vinay, D.O. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of conversion from a calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix® (belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function (SGF) following kidney transplantation. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Delayed Graft Function, Kidney Transplant
- What is being tested?
- Belatacept and Calcineurin Inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Jun 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
- All patients (> 18 years) who have received a deceased donor transplant and are at risk for SGF/DGF will be studied
- All gender and ethnicities will be considered in this study
- At risk for SGF/DGF is defined as:
- ECD (Extended Criteria Donor) donor kidney recipients
- ECD is defined as a donor over the age of 60 or age 50 to 60 with 2 of the following risk factors:
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- Terminal creatinine > 1.5 mg/dL
- History of Hypertension
- Death due to cerebrovascular accident
- Donations after cardiac death (DCD) kidney recipients
- Donor organs with an actual cold ischemia time (CIT) > 19 hours
- Recipients of donor organs with a terminal creatinine > 1.5 mg/dL
- Only patients who receive Thymoglobulin induction and CNI maintenance at time of randomization will be considered for the study
- Men and women, 18 to 70 years of age
- Reproductive status: Definition of Women of Child-Bearing Potential (WOCBP). WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal.
- Post-menopause is defined as:
- Women who have had amenorrhea for >= 12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH)level > 35 mIU/mL
- Women who have irregular menstrual periods and a documented serum FSH level > 35 mIU/mL
- Women who are taking hormone replacement therapy
- The following are WOCBP:
- Women using the following methods to prevent pregnancy: oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides).
- Women who are practicing abstinence
- Women who have a partner who is sterile (due to vasectomy)
- WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized
- WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug.
- Women must not be breast-feeding
- Sexually active fertile men must use effective birth control if their partners are WOCBP
Who cannot join
- Seronegative or unknown EBV (Epstein Barr Virus) serostatus (due to the risk of posttransplant lymphoproliferative disorder, PTLD) predominantly involving the central nervous system
- 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
- Rejection episode before randomization
- Anatomic cause of SGF/DGF such as urinary leak, obstruction or thrombosis
- Patients with a prior or concurrent non-renal solid organ transplant
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- Patients with living donor kidneys
- Patients with pediatric kidneys (age of less than 5 years)
- Dual kidney transplants (from the same donor)
- Immunologically high risk patients with a positive crossmatch pre- transplantation or donor specific antibody (DSA) > 5000 MFI
- ABO Incompatible transplantation
- Patients with HIV
- Subjects with any active infection or other contraindication that would normally exclude transplantation
- Patients with a history of malignancy in the last 5 years except non- melanoma skin cancer
- Baseline white blood cell count less than 2,000
- Baseline hemoglobin less than 8 g/dL
- Patients with prior allergic reactions to belatacept
- Patients with prior allergic reactions to thymoglobulin
- Sex and Reproductive status - see WOCBP information in inclusion above
- Subjects currently receiving immunosuppressive agent(s) for other indications such as an autoimmune disease or subjects with comorbidities that treatment with such agents are likely during the trial.
- Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
- Subjects previously treated with belatacept
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Mount Sinai School of Medicine Recanati/Miller Transplantation Institute
New York, New York, 10029
Vinay Nair, D.O., 212-659-8086, Vinay.Nair@mountsinai.org
Brandy Haydel, CCRC, 212-241-0255, Brandy.Haydel@mountsinai.org
About this study
Official title: A Randomized Trial of Early Conversion From Calcineurin Inhibitors (CNI) to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function
The purpose of this study is to evaluate the safety and efficacy of conversion from a calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix® (belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function (SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they have developed SGF or DGF they will be randomized to convert to Belatacept or continue on their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal biopsy at Month 12 post transplant.
Research Hypotheses:
Read more
Primary Hypotheses:
- Kidneys with slow or delayed graft function are more susceptible to acute and long-term CNI toxicity
- Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have improved 1 year calculated GFR.
Key Secondary Hypotheses:
- Renal Histology: Belatacept converted patients will have a lower chronic allograft damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA) score as calculated by Banff criteria at 1 year post- transplant
- Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections can 1) directly assess CNI induced kidney injury and 2) improve the prediction of patients that benefit in early belatacept conversion.
- Conditions
- Delayed Graft Function, Kidney Transplant
- Being tested
- Belatacept, Calcineurin Inhibitor
- Keywords
- Delayed Graft Function, Renal Transplantation, Kidney Transplant
- Medical subject headings
- Delayed Graft Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelataceptDrug
Also called Nulojix
Calcineurin InhibitorDrug
Also called Prograf, Tacrolimus, Cyclosporine
| Study group | Role | What they receive |
|---|---|---|
| Belatacept | Experimental | Subjects will be converted from standard of care CNI therapy to Belatacept 10 mg/kg IV on post renal transplant Day 7 (+/- 3 days). As suggested in the package insert for de novo dosing, further dosing of belatacept will be given as 10 mg/kg IV at weeks 2, 4, 8 and 12 then 5 mg/kg at week 16 and then every 4 weeks (+/- 5 days) through week 52. CNI will be stopped during the first belatacept infusion. Receives: Drug: Belatacept |
| Calcineurin Inhibitor | Active comparator | Patients randomized to this arm will remain on the current CNI as prescribed by post-transplant standard of care therapy. Receives: Drug: Calcineurin Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
cGFR
Serum creatinine will be checked at each study visit from which GFR will be calculated. 12 month 4 variable MDRD calculated GFR will be compared between the belatacept conversion group and the calcineurin inhibitor group.
Measured: 12 months
Secondary outcomes (9)
Renal Histology
Chronic Allograft Damage Index (CADI) and Interstitial Fibrosis/Tubular Atrophy (IFTA) renal pathology scores will be assessed by a local pathologist. CADI and IF/TA will be recorded at baseline (reperfusion biopsy) and at the 1 year protocol biopsy. The average progression of CADI and IF/TA will be compared in both groups and the average absolute CADI and IF/TA scores will be compared in both groups at 1 year post transplant.
Measured: 12 months
Biomarker profile
The results of urine biomarkers (clusterin) will be correlated with the development of the primary and secondary endpoints in both groups. In this manner the investigators will be able to understand which genes/proteins are primarily altered by injury and assess how belatacept affects this process.
Measured: 12 months
Duration of Delayed (or slow) Graft Function
The average duration of DGF/SGF will be compared in both belatacept and CNI groups
Measured: 12 months
Incidence of Acute Rejection
Acute rejection by month 12 will be assessed by a local pathologist using the Banff 97 working classification of kidney transplant pathology. All biopsies will be interpreted locally for purposes of the study.
Measured: 12 months
New Onset Diabetes
Subjects will be evaluated for post-transplant diabetes at visits after week 4.
Measured: 12 months
Blood Pressure Control
Subjects are to be evaluated at each clinic visit to assess the need for adjustment of antihypertensive medication in order to achieve a BP of < 130/80 mmHg. Average systolic and diastolic blood pressure in both groups at Month 12, number of antihypertensive medications and change in intensity of hypertension treatment will be observed.
Measured: 12 months
Dyslipidemia
Cholesterol levels in both groups, number of patients on dyslipidemic therapy at month 12 and change in intensity of dyslipidemia therapy will be observed
Measured: 12 months
Graft Survival
Graft survival will be observed in both groups and compared at 12 months post-transplant
Measured: 12 Months
Patient survival
Patient survival will be observed in both groups and compared at 12 months post-transplant
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2017 (estimated)
- Study completionJun 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Delayed Graft FunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nair, Vinay, D.O.
- Collaborators
- Icahn School of Medicine at Mount Sinai, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Vinay Nair, D.O., Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01837043
- Sponsor's protocol ID
- IM103-057
- Other IDs
- 13-00174
- Status last verified
- Jan 2017
- First submitted
- 16 Apr 2013
- Last updated
- 30 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Early Conversion From Calcineurin Inhibitors (CNI) to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function
- ClinicalTrials.gov ID
- NCT01837043
- Acronym / sponsor ID
- IM103-057
- Conditions
- Delayed Graft Function, Kidney Transplant
- Keywords
- Delayed Graft Function, Renal Transplantation, Kidney Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Nair, Vinay, D.O.
- Collaborators
- Icahn School of Medicine at Mount Sinai, Bristol-Myers Squibb
- Study start
- Jun 2013
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 22 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of conversion from a calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix® (belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function (SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they have developed SGF or DGF they will be randomized to convert to Belatacept or continue on their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal biopsy at Month 12 post transplant.
Research Hypotheses:
Primary Hypotheses:
- Kidneys with slow or delayed graft function are more susceptible to acute and long-term CNI toxicity
- Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have improved 1 year calculated GFR.
Key Secondary Hypotheses:
- Renal Histology: Belatacept converted patients will have a lower chronic allograft damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA) score as calculated by Banff criteria at 1 year post- transplant
- Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections can 1) directly assess CNI induced kidney injury and 2) improve the prediction of patients that benefit in early belatacept conversion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Belatacept | Experimental | Drug: BelataceptSubjects will be converted from standard of care CNI therapy to Belatacept 10 mg/kg IV on post renal transplant Day 7 (+/- 3 days). As suggested in the package insert for de novo dosing, further dosing of belatacept will be given as 10 mg/kg IV at weeks 2, 4, 8 and 12 then 5 mg/kg at week 16 and then every 4 weeks (+/- 5 days) through week 52. CNI will be stopped during the first belatacept infusion. |
| Calcineurin Inhibitor | Active comparator | Drug: Calcineurin InhibitorPatients randomized to this arm will remain on the current CNI as prescribed by post-transplant standard of care therapy. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.
- All patients (> 18 years) who have received a deceased donor transplant and are at risk for SGF/DGF will be studied
- All gender and ethnicities will be considered in this study
- At risk for SGF/DGF is defined as:
- Terminal creatinine > 1.5 mg/dL
Key exclusion criteria (24 listed)
- Seronegative or unknown EBV (Epstein Barr Virus) serostatus (due to the risk of posttransplant lymphoproliferative disorder, PTLD) predominantly involving the central nervous system
- 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
- Rejection episode before randomization
- Anatomic cause of SGF/DGF such as urinary leak, obstruction or thrombosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelataceptAlso: Nulojix | Drug | Belatacept |
| Calcineurin InhibitorAlso: Prograf, Tacrolimus, Cyclosporine | Drug | Calcineurin Inhibitor |
Primary outcome
cGFR
Time frame: 12 months
Serum creatinine will be checked at each study visit from which GFR will be calculated. 12 month 4 variable MDRD calculated GFR will be compared between the belatacept conversion group and the calcineurin inhibitor group.
9 secondary outcomes
Renal Histology
Time frame: 12 months
Biomarker profile
Time frame: 12 months
Duration of Delayed (or slow) Graft Function
Time frame: 12 months
Incidence of Acute Rejection
Time frame: 12 months
New Onset Diabetes
Time frame: 12 months
Blood Pressure Control
Time frame: 12 months
Dyslipidemia
Time frame: 12 months
Graft Survival
Time frame: 12 Months
Patient survival
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vinay Nair, D.O. principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belatacept and Calcineurin Inhibitor in people with Delayed Graft Function and Kidney Transplant, run by Nair, Vinay, D.O. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vinay Nair, D.O. (212-659-8086, Vinay.Nair@mountsinai.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cGFR (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2017.