Primary Renal Allograft CandidatePhase 2NCT01856257

Open-Label Phase 2 Trial of a Steroid-Free, CNI-Free, Belatacept-Based Immunosuppressive Regimen

A Phase 2 study testing Anti-thymocyte Globulin (Rabbit), belatacept and methylprednisolone in people with Primary Renal Allograft Candidate and Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The primary objective is to evaluate a NULOJIX® (belatacept) based regimens as a means of improving long-term graft function without increasing the risks of immunologic graft injury by avoiding both calcineurin inhibitors (CNIs) and corticosteroids. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Primary Renal Allograft Candidate, Kidney Transplantation
What is being tested?: Anti-thymocyte Globulin (Rabbit), belatacept and methylprednisolone
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 71 participants
Where: 3 sitesUnited States
Study dates: Jul 2013to Apr 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or Female, 18-65 years of age at the time of enrollment;
Ability to understand and provide written informed consent;
Candidate for primary renal allograft from either living or deceased donor;
No known contraindications to study therapy using NULOJIX® (belatacept);
Female participants of childbearing potential must have a negative pregnancy test upon study entry;
Participants with reproductive potential must agree to use an appropriate method(s) of birth control as outlined in the CellCept® , Myfortic® or generic package labeling during participation in the study and for 4 months following completion of the study;

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No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
Negative crossmatch or Panel Reactive Antibodies (PRA) of 0% on historic and current sera, as determined by each participating study center;
A documented negative tuberculosis (TB) test within the 6 months prior to transplant. If documentation is not present at the time of transplantation, and the subject does not have any risk factors for TB, a TB-specific interferon gamma release assay (IGRA) may be performed.

Who cannot join

Need for multi-organ transplant;
Recipient of previous organ transplant;
Epstein-Barr Virus (EBV) seronegative (or unknown) recipients;
Active infection including hepatitis B, hepatitis C, or human Immunodeficiency Virus (HIV);
Individuals who have required treatment with prednisone or other immunosuppressive drugs within 1 year prior to transplant;
Individuals undergoing transplant using organs from extended criteria donor (ECD) or donation after cardiac death (DCD) donors;

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Histocompatibility antigen (HLA) identical living donors;
Individuals at significant risk of early recurrence of the primary renal disease including focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN) type 2 or any other disease that in the opinion of the investigator is at increased likelihood of recurrence and which may result in rapid decline in renal function;
Known history of thrombotic events or risk factors, including any of the following:
Factor V Leiden, elevated homocysteine, positive lupus anticoagulant, elevated anticardiolipin antibody, heparin-induced thrombocytopenia,
A family history of a heritable thrombotic condition,
Recurrent deep vein thrombosis (DVT) or pulmonary emboli (PE),
Unexplained stillborn infant or recurrent spontaneous abortion or other congenital or acquired thrombotic disorder.
At the discretion of the investigator, a history of thrombosis of a dialysis access graft, fistula, or indwelling catheter/device may not be considered an exclusion criterion.
Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;
Use of investigational drugs within 4 weeks of enrollment;
Known hypersensitivity to mycophenolate mofetil (MMF)or any of the drug's components;
Administration of live attenuated vaccine(s) within 8 weeks of enrollment;
Blood type A2 and A2B donors into blood type B recipients.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Emory University
Atlanta, Georgia, 30322
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of California, San Francisco
San Francisco, California, 94143

Other trials in United States

About this study

Official title: Steroid and Tacrolimus Avoidance Using NULOJIX® (Belatacept) in Renal Transplantation (CTOT-16)

Read the detailed description

Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. Transplant recipients have to take anti-rejection medications to prevent their immune system (the body's natural defense system against illness) from rejecting their new kidney. Most patients who receive a kidney transplant must take these anti-rejection medications for the rest of their lives, or for as long as the kidney continues to work.

The purpose of this study is to determine if NULOJIX® (belatacept), will minimize serious long term side effects seen with anti-rejection medications while still protecting the transplanted kidney from damage. The researchers also want to learn more about the safety of this treatment and the long term health of the transplanted kidney.

Conditions: Primary Renal Allograft Candidate, Kidney Transplantation
Being tested: Anti-thymocyte Globulin (Rabbit), belatacept, methylprednisolone, basiliximab, mycophenolate mofetil
Keywords: Kidney Transplantation, Transplantation, NULOJIX, belatacept, chronic immunosuppression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Anti-thymocyte Globulin (Rabbit)Biological
Also called Thymoglobulin®, ATG (Rabbit)
The target dosage is 6mg/kg total over 3 to 4 days. The recommended route of administration is intravenous infusion using a high-flow vein.
belataceptBiological
Also called NULOJIX®
Participants will receive belatacept at a dose of 10mg/kg up on day 1, 5, 14, 28, 56 and 84. After 84 days, subjects will receive a maintenance dose of 5 mg/kg every 4 weeks until completion of the trial.
methylprednisoloneDrug
Also called Medrol®
Methylprednisolone will be administered at a target dose of 500 mg beginning on the day of transplant, and tapered to 250 mg day 1 post-transplant, 125 mg day 2 post-transplant, 60 mg day 3 post-transplant, 30 mg day 4 post-transplant and day 5 post-transplant 0 mg if therapeutic tacrolimus level achieved for groups 1 and 3.
basiliximabBiological
Also called Simulect®
Basiliximab will be administered in two doses of 20 mg each.
mycophenolate mofetilDrug
Also called MMF, CellCept®, mycophenolate acid
Mycophenolate Mofetil will be administered at a target dose of 1000 mg orally twice a day. Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.
tacrolimusDrug
Also called Prograf®
The site investigator will identify a starting tacrolimus dose at their discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. The dose will be adjusted to 5-8ng/ml for the active comparator arm (thymoglobulin + tacrolimus + MMF arm) or tapered off in the experimental arm (basiliximab + 20 weeks of tacrolimus + MMF + belatacept).

Study groups in NCT01856257
Study group	Role	What they receive
Thymoglobulin®+tacrolimus+MMF	Active comparator	Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF) Receives: Biological: Anti-thymocyte Globulin (Rabbit); Drug: methylprednisolone; Drug: mycophenolate mofetil; Drug: tacrolimus
Thymoglobulin®+belatacept+MMF	Experimental	Induction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF) Receives: Biological: Anti-thymocyte Globulin (Rabbit); Biological: belatacept; Drug: methylprednisolone; Drug: mycophenolate mofetil
Basiliximab+20 weeks of tacrolimus+MMF + belatacept	Experimental	Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent. Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator. Receives: Biological: belatacept; Drug: methylprednisolone; Biological: basiliximab; Drug: mycophenolate mofetil; Drug: tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant
eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI):
- A score of ≥90 means kidney function is normal.
- A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.
- Scores between 30 and 59 indicates moderately reduced kidney function.
- Scores between 15 and 29 indicate severely reduced kidney function.
- Scores below 15 indicate very severe or end stage kidney failure.
Measured: Week 52

Secondary outcomes (30)

Count of Participants With Biopsy Proven Acute Rejection By Wk 52 Post-Transplant
Biopsy proven acute rejection definition: histologic evidence of a Banff grade of ≥1A per local pathologist.
Measured: Transplantation through Week 52
Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant
eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI):
- A score of ≥90 means kidney function is normal.
- A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.
- Scores between 30 and 59 indicates moderately reduced kidney function.
- Scores between 15 and 29 indicate severely reduced kidney function.
- Scores below 15 indicate very severe or end stage kidney failure.
Measured: Week 52
Count of Participants by CKD Stage at Wk 52
The stages of Chronic Kidney Disease are defined using the participant's GFR value:
- Stage 1 if GFR value is ≥90 ( kidney function is normal)
- Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease)
- Stage 3A if 45 ≤ GFR < 60*
- Stage 3B if 30 ≤ GFR < 45*
- Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function)
- Stage 5 if GFR < 15 (severe or end stage kidney failure).
Stages 3A and 3B indicate moderately reduced kidney function.*
Measured: Week 52
Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant
The stages of Chronic Kidney Disease (CKD) are defined using the participant's GFR value:
- Stage 1 if GFR value is ≥ 90 (kidney function is normal)
- Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease)
- Stage 3A if 45 <= GFR < 60*
- Stage 3B if 30 <= GFR < 45*
- Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function)
- Stage 5 if GFR < 15 (severe or end stage kidney failure).
Stages 3A abd 3B indicate moderately reduced kidney function.*
Measured: Week 52
Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant
The estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation (MDRD):
- A score of ≥ 90 means kidney function is normal.
- A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.
- Scores between 30 and 59 indicates moderately reduced kidney function.
- Scores between 15 and 29 indicate severely reduced kidney function.
- Scores below 15 indicate severe or endstage kidney failure.
Measured: Week 52
The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant
The estimated Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI):
- A score of ≥ 90 means kidney function is normal.
- A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease.
- Scores between 30 and 59 indicates moderately reduced kidney function.
- Scores between 15 and 29 indicate severely reduced kidney function.
- Scores below 15 indicate very severe or endstage kidney failure.
An estimate of the slope, or change over time, in eGFR was produced using standard statistical linear modeling procedures. The estimate was then re-scaled so that it could be interpreted as a change in eGFR per month. Positive numbers indicate increasing kidney function.
Larger numbers indicate greater change in kidney function.
Measured: Day 28 through Week 52 Post-Transplant
Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant
Delayed grafted function is defined as dialysis in the first week on one or more occasions for any indication other than the treatment of acute hyperkalemia in the setting of otherwise acceptable renal function.
Measured: Transplantation through Week 52
Count of Participants With Acute Cellular Rejection Grade ≥ IA Defined by Banff 2007 Criteria By Wk 52 Post-Transplant
Acute cellular rejection occurs when lesions at the site of the graft characteristically are infiltrated with large numbers of lymphocytes and macrophages that cause tissue damage. Acute cellular rejection for this endpoint is defined as a grade equal to or greater than IA by Banff 2007 criteria as determined by local pathology.
Measured: Transplantation through Week 52
Count of Participants by Severity of First Acute Cellular Rejection by Wk 52 Post-Transplant
Acute cellular rejection occurs when lesions at the site of the graft characteristically are infiltrated with large numbers of lymphocytes and macrophages that cause tissue damage. Acute cellular rejection for this endpoint is defined as a grade equal to or greater than IA by Banff 2007 criteria as determined by local pathology. Severity is graded as IA, IB, IIA, IIB, or III, with IA being the mildest form of cellular rejection and III being the most severe form of cellular rejection. Originally it was 2 endpoints but all participants' highest grade was also their first grade so only reporting their first grade.
Measured: Transplantation through Week 52
Count of Participants With Antibody Mediated Rejection by Wk 52 Post-Transplant
Antibody mediated rejection is defined by diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury and was determined by local pathology.
Measured: Transplantation through Week 52
Type of Rejection Classified by Pathologist - For Cause Kidney Biopsies
Upon having a biopsy performed, persons often receive treatment for rejection based on the results of the biopsy, which may or may not have shown signs of rejection. Details of local biopsy findings are presented here for rejection. Acronyms and abbreviations are defined as follows:
- ACR= Acute T-Cell Mediated rejection
- AMR= Acute Antibody-mediated rejection
- Chr. AMR=Chronic Antibody Mediated Rejection
- Gd.=Grade
- IFTA=Interstitial Fibrosis and Tubular Atrophy
Measured: Transplantation through Week 52
Type of Treatment for Detected Graft Rejection
Upon having a biopsy performed, persons often receive treatment for rejection based on the results of the biopsy, which may or may not have shown signs of rejection. Details of treatment are presented here for rejection. Acronyms and abbreviations are defined below.
ATG=Thymoglobulin
Measured: Transplantation through Week 52
Count of Participants With De Novo Anti-Donor Histocompatibility Antigen (HLA) Antibodies at Wk 52 Post-Transplant
The presence of antibodies reactive to Histocompatibility Antigen (HLA) molecules expressed on the renal allograft have been associated with both acute and chronic injury to the transplanted kidney. The development of de novo anti donor HLA antibodies may mean a person is more likely to reject the graft.
No data available.
Measured: Week 52
Count of Participants With Either New Onset Diabetes After Transplant (NODAT) or Impaired Fasting Glucose (IFG) at Week 52 Post-Transplant -Based on Criteria Specified by the ADA and WHO
New onset diabetes is the development of diabetes post-kidney transplant. It was identified by the clinical sites caring for each participant and reported directly in the clinical database. Impaired fasting glucose (IFG) is a determination made by referencing glucose measurements obtained from a standard chemistry panel. Any fasting glucose measure that is between 110 and 125 mg/dL is classified as IFG.
Acronyms: American Diabetes Association (ADA); World Health Organization (WHO).
Measured: Transplantation through Week 52
Count of Participants With Treated Diabetes Between Day 14 and Wk 52 Post-Transplant
Treated diabetes is defined as receipt of any oral medication or insulin for the treatment of diabetes for >14 days.
Measured: Day 14 through week 52
Hemoglobin A1c (HbA1c) Measurements Over Time
Hemoglobin A1c (HbA1c) measures the average blood glucose levels over 8-12 weeks, thus acting as a useful long-term gauge of blood glucose control:
- A value below 6.0% reflects normal levels,
- 6.0% to 6.4% reflects prediabetes, and
- a value of ≥ 6.5% reflects diabetes.
Measured: Baseline (Pre-Transplant) and Days 28 and -84, and Weeks 28, -36, and -52 Post-Transplant
Standardized Blood Pressure Measurement at Wk 52 Post-Transplant
A blood pressure measurement consists of two numbers: the systolic and diastolic pressures. Systolic pressure measures the pressure in blood vessels when the heart beats. Diastolic pressure measures the pressure in blood vessels between beats of the heart.
- Systolic measures of <120 and diastolic measures of <80 are considered normal.
- Systolic measures of 120-139 and diastolic measures of 80-89 are considered at risk (or pre-hypertension).
- Systolic measures of ≥140 and diastolic measures of ≥90 are considered high.
Measured: Week 52
Count of Participants With Use of Anti-hypertensive Medication at Wk 52 Post-Transplant
Anti-hypertensive medications are a class of drugs that are used to treat hypertension. The medications seek to prevent the complications of high blood pressure, such as stroke and myocardial infarction.
Measured: Week 52
Fasting Lipid Profile at Baseline (Pre-Transplant)
A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided:
- Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease
- LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease
- HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease
- Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and
- Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
Measured: Baseline
Fasting Lipid Profile at Wk 28 Post-Transplant
A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided:
- Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease
- LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease
- HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease
- Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and
- Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
Measured: Week 28
Fasting Lipid Profile at Wk 52 Post-Transplant
A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided:
- Total cholesterol: 75-169 mg/dL if age ≤ 20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease
- LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease
- HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease
- Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and
- Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
Measured: Week 52
Count of Participants With Use of Lipid Lowering Medications at Baseline and Wk 28 and Wk 52 Post-Transplant
Lipid lowering medications are used in the treatment of high levels of fats (lipids), such as cholesterol in blood.
Measured: Baseline (Pre-Transplant), Week 28, and Week 52
Total Daily Prescribed Pill Count
This is a measure of the total number of pills a participant was prescribed on a given day
Measured: Day 28, Day 84, Week 28, Week 36, and Week 52
Count of Participant Deaths or Graft Loss by Wk 52 Post-Transplant
This measure counts deaths and graft loss occurring at any point post transplantation. Graft loss is defined as 90 days of dialysis dependency.
Measured: Transplantation through Week 52
Count of Participants With Graft Rejection by Wk 52 Post-Transplant
The number of participants who were treated by their local physician for any type of rejection including, but not limited to cellular rejection and antibody- mediated rejection of the transplanted kidney regardless of the presence of a biopsy.
Measured: Transplantation through Week 52
Count of Participants Experiencing ≥ 1 Adverse Event (AEs) or Serious Adverse Events (SAEs) by Wk 52
Adverse events were collected systematically from enrollment through Wk 52, the last study visit. Provided are numbers of participants with ≥ 1 adverse event (serious or non-serious adverse events) by treatment arm.
Measured: Enrollment through Week 52
Count of Participants With Infections Requiring Hospitalization or Systemic Therapy by Wk 52 Post-Transplant
Infections of certain types (i.e., excluding those identified in the protocol as occurring commonly in this study population) were required to be reported as a serious adverse event if they required either inpatient hospitalization or prolongation of a current hospitalization.
Measured: Transplantation through Week 52
Count of Participants With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia (Local Center Monitoring) as Adverse Events by Wk 52 Post-Transplant
Viral infections following renal transplantation is significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during the study, using participant blood samples. Displayed are counts of participants who experienced BKV and CMV viremia as adverse events by treatment arm.
Measured: Transplantation through Week 52
Count of Participants With Epstein-Barr Virus (EBV) Infection as Reported on the Case Report Form as Adverse Events
Viral infections following renal transplantation, including but not limited to EBV infection, is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss.
Measured: Transplantation through Week 52
Count of Participants With Fever > 39 Degrees Celsius and Blood Pressure < 90 mmHg Within 24 Hours of Onset of Transplant Procedure
Temperature of >39 degrees Celsius (e.g., 102.2 degrees Fahrenheit) would be an indication of fever most often in response to an infection or illness. Systolic blood pressure <90mm Hg would be an indication of low blood pressure.
Measured: Within 24 Hours of transplant procedure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2013Apr 2016

First posted17 May 2013 (estimated)
Study startJul 2013
Primary completionApr 2016
Study completionApr 2016

Why it stopped: Safety: Stopping rule not met.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary Renal Allograft CandidateStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
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: 71 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01856257
Sponsor's protocol ID: DAIT CTOT-16
Status last verified: Sep 2026
First submitted: 14 May 2013
Last updated: 24 Sep 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Participant level data access and additional relevant materials will be made available upon completion of the trial.

Publications

Mannon RB, Armstrong B, Stock PG, Mehta AK, Farris AB, Watson N, Morrison Y, Sarwal M, Sigdel T, Bridges N, Robien M, Newell KA, Larsen CP. Avoidance of CNI and steroids using belatacept-Results of the Clinical Trials in Organ Transplantation 16 trial. Am J Transplant. 2020 Dec;20(12):3599-3608. doi: 10.1111/ajt.16152. Epub 2020 Jul 13.
PubMed 32558199

Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Steroid and Tacrolimus Avoidance Using NULOJIX® (Belatacept) in Renal Transplantation (CTOT-16)
ClinicalTrials.gov ID: NCT01856257
Acronym / sponsor ID: DAIT CTOT-16
Conditions: Primary Renal Allograft Candidate, Kidney Transplantation
Keywords: Kidney Transplantation, Transplantation, NULOJIX, belatacept, chronic immunosuppression
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Safety: Stopping rule not met.
Enrolment: 71 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: Clinical Trials in Organ Transplantation
Study start: Jul 2013
Primary completion: Apr 2016 (actual)
Study completion: Apr 2016 (actual)
First posted: 17 May 2013 (estimated)
Results: Posted 7 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Thymoglobulin®+tacrolimus+MMF	Active comparator	Biological: Anti-thymocyte Globulin (Rabbit), Drug: methylprednisolone, Drug: mycophenolate mofetil, Drug: tacrolimusInduction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)
Thymoglobulin®+belatacept+MMF	Experimental	Biological: Anti-thymocyte Globulin (Rabbit), Biological: belatacept, Drug: methylprednisolone, Drug: mycophenolate mofetilInduction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF)
Basiliximab+20 weeks of tacrolimus+MMF + belatacept	Experimental	Biological: belatacept, Drug: methylprednisolone, Biological: basiliximab, Drug: mycophenolate mofetil, Drug: tacrolimusInduction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent. Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Male or Female, 18-65 years of age at the time of enrollment;
Ability to understand and provide written informed consent;
Candidate for primary renal allograft from either living or deceased donor;
No known contraindications to study therapy using NULOJIX® (belatacept);
Female participants of childbearing potential must have a negative pregnancy test upon study entry;

Key exclusion criteria (19 listed)

Need for multi-organ transplant;
Recipient of previous organ transplant;
Epstein-Barr Virus (EBV) seronegative (or unknown) recipients;
Active infection including hepatitis B, hepatitis C, or human Immunodeficiency Virus (HIV);
Individuals who have required treatment with prednisone or other immunosuppressive drugs within 1 year prior to transplant;

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
Anti-thymocyte Globulin (Rabbit)Also: Thymoglobulin®, ATG (Rabbit)The target dosage is 6mg/kg total over 3 to 4 days. The recommended route of administration is intravenous infusion using a high-flow vein.	Biological	Thymoglobulin®+belatacept+MMF, Thymoglobulin®+tacrolimus+MMF
belataceptAlso: NULOJIX®Participants will receive belatacept at a dose of 10mg/kg up on day 1, 5, 14, 28, 56 and 84. After 84 days, subjects will receive a maintenance dose of 5 mg/kg every 4 weeks until completion of the trial.	Biological	Basiliximab+20 weeks of tacrolimus+MMF + belatacept, Thymoglobulin®+belatacept+MMF
methylprednisoloneAlso: Medrol®Methylprednisolone will be administered at a target dose of 500 mg beginning on the day of transplant, and tapered to 250 mg day 1 post-transplant, 125 mg day 2 post-transplant, 60 mg day 3 post-transplant, 30 mg day 4 post-transplant and day 5 post-transplant 0 mg if therapeutic tacrolimus level achieved for groups 1 and 3.	Drug	Basiliximab+20 weeks of tacrolimus+MMF + belatacept, Thymoglobulin®+belatacept+MMF, Thymoglobulin®+tacrolimus+MMF
basiliximabAlso: Simulect®Basiliximab will be administered in two doses of 20 mg each.	Biological	Basiliximab+20 weeks of tacrolimus+MMF + belatacept
mycophenolate mofetilAlso: MMF, CellCept®, mycophenolate acidMycophenolate Mofetil will be administered at a target dose of 1000 mg orally twice a day. Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.	Drug	Basiliximab+20 weeks of tacrolimus+MMF + belatacept, Thymoglobulin®+belatacept+MMF, Thymoglobulin®+tacrolimus+MMF
tacrolimusAlso: Prograf®The site investigator will identify a starting tacrolimus dose at their discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. The dose will be adjusted to 5-8ng/ml for the active comparator arm (thymoglobulin + tacrolimus + MMF arm) or tapered off in the experimental arm (basiliximab + 20 weeks of tacrolimus + MMF + belatacept).	Drug	Basiliximab+20 weeks of tacrolimus+MMF + belatacept, Thymoglobulin®+tacrolimus+MMF

Primary outcome

Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant
Time frame: Week 52
eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): * A score of ≥90 means kidney function is normal. * A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. * Scores between 30 and 59 indicates moderately reduced kidney function. * Scores between 15 and 29 indicate severely reduced kidney function. * Scores below 15 indicate very severe or end stage kidney failure.

30 secondary outcomes

Count of Participants With Biopsy Proven Acute Rejection By Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant
Time frame: Week 52
Count of Participants by CKD Stage at Wk 52
Time frame: Week 52
Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant
Time frame: Week 52
Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant
Time frame: Week 52
The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant
Time frame: Day 28 through Week 52 Post-Transplant
Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants With Acute Cellular Rejection Grade ≥ IA Defined by Banff 2007 Criteria By Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants by Severity of First Acute Cellular Rejection by Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants With Antibody Mediated Rejection by Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Type of Rejection Classified by Pathologist - For Cause Kidney Biopsies
Time frame: Transplantation through Week 52
Type of Treatment for Detected Graft Rejection
Time frame: Transplantation through Week 52
Count of Participants With De Novo Anti-Donor Histocompatibility Antigen (HLA) Antibodies at Wk 52 Post-Transplant
Time frame: Week 52
Count of Participants With Either New Onset Diabetes After Transplant (NODAT) or Impaired Fasting Glucose (IFG) at Week 52 Post-Transplant -Based on Criteria Specified by the ADA and WHO
Time frame: Transplantation through Week 52
Count of Participants With Treated Diabetes Between Day 14 and Wk 52 Post-Transplant
Time frame: Day 14 through week 52
Hemoglobin A1c (HbA1c) Measurements Over Time
Time frame: Baseline (Pre-Transplant) and Days 28 and -84, and Weeks 28, -36, and -52 Post-Transplant
Standardized Blood Pressure Measurement at Wk 52 Post-Transplant
Time frame: Week 52
Count of Participants With Use of Anti-hypertensive Medication at Wk 52 Post-Transplant
Time frame: Week 52
Fasting Lipid Profile at Baseline (Pre-Transplant)
Time frame: Baseline
Fasting Lipid Profile at Wk 28 Post-Transplant
Time frame: Week 28
Fasting Lipid Profile at Wk 52 Post-Transplant
Time frame: Week 52
Count of Participants With Use of Lipid Lowering Medications at Baseline and Wk 28 and Wk 52 Post-Transplant
Time frame: Baseline (Pre-Transplant), Week 28, and Week 52
Total Daily Prescribed Pill Count
Time frame: Day 28, Day 84, Week 28, Week 36, and Week 52
Count of Participant Deaths or Graft Loss by Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants With Graft Rejection by Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants Experiencing ≥ 1 Adverse Event (AEs) or Serious Adverse Events (SAEs) by Wk 52
Time frame: Enrollment through Week 52
Count of Participants With Infections Requiring Hospitalization or Systemic Therapy by Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia (Local Center Monitoring) as Adverse Events by Wk 52 Post-Transplant
Time frame: Transplantation through Week 52
Count of Participants With Epstein-Barr Virus (EBV) Infection as Reported on the Case Report Form as Adverse Events
Time frame: Transplantation through Week 52
Count of Participants With Fever > 39 Degrees Celsius and Blood Pressure < 90 mmHg Within 24 Hours of Onset of Transplant Procedure
Time frame: Within 24 Hours of transplant procedure

Results and safety

Results posted to the registry on 7 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Tac	29	26
Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Belatacept	29	28
Induction:MEDROL+Simulect+Tac, Maintenance:MMF+Belatacept	11	11
Enrolled, Not Randomized	2	0

Primary outcome: Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant

Time frame: Week 52. Mean (Standard Deviation). Unit: mL/min/1.73m^2

Measure	Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Tac n = 26	Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Belatacept n = 27	Induction:MEDROL+Simulect+Tac, Maintenance:MMF+Belatacept n = 11
Value	59.2 (19.9)	61.5 (23.3)	63.0 (17.4)

Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Tac vs Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Belatacept: Mean Difference (Final Values): 3.512 (95% CI -7.999 to 15.024), p = 0.544, Mixed Models Analysis
Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Tac vs Induction:MEDROL+Simulect+Tac, Maintenance:MMF+Belatacept: Mean Difference (Final Values): 4.820 (95% CI -10.481 to 20.121), p = 0.531, Mixed Models Analysis

Population analysed: Intent-to-treat population with available data at week 52

30 secondary outcomes are reported in the full results.

Adverse events

Time frame: Enrollment through end of study (up to Week 52). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Tac	19 of 29 (65.5%)	15 of 29 (51.7%)	2 of 29
Induction:MEDROL+Thymoglobulin, Maintenance:MMF+Belatacept	21 of 29 (72.4%)	24 of 29 (82.8%)	0 of 29
Induction:MEDROL+Simulect+Tac, Maintenance:MMF+Belatacept	6 of 11 (54.5%)	7 of 11 (63.6%)	0 of 11
Enrolled, Not Randomized	0 of 2 (0%)	0 of 2 (0%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 32558199Mannon RB, Armstrong B, Stock PG, Mehta AK, Farris AB, Watson N, Morrison Y, Sarwal M, Sigdel T, Bridges N, Robien M, Newell KA, Larsen CP. Avoidance of CNI and steroids using belatacept-Results of the Clinical Trials in Organ Transplantation 16 trial. Am J Transplant. 2020 Dec;20(12):3599-3608. doi: 10.1111/ajt.16152. Epub 2020 Jul 13.
National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Participant level data access and additional relevant materials will be made available upon completion of the trial.

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.

Kenneth Newell, MD, PhD principal investigator

Emory University

Roslyn B. Mannon, M.D. study chair

University of Alabama at Birmingham

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 inclusion and 19 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: stopped early, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

Yes. Results are posted in the registry (first posted 7 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant (time frame: Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01856257, which also lists 1 linked publication.

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 24 Sep 2026.