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

NCT01856257 | Terminated Phase 2 Results DMC

• 1 other identifier: DAIT CTOT-16
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Primary Renal Allograft Candidate; Kidney Transplantation

Keywords

Kidney Transplantation; Transplantation; NULOJIX; belatacept; chronic immunosuppression

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 52

Secondary Outcomes (30)

• Count of Participants With Biopsy Proven Acute Rejection By Wk 52 Post-Transplant

  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

  Week 52

• Count of Participants by CKD Stage at Wk 52

  Week 52

• Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant

  Week 52

• Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant

  Week 52

Study Arms (3)

Thymoglobulin®+tacrolimus+MMF

ACTIVE COMPARATOR

Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)

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)

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.

Biological: belatacept; Drug: methylprednisolone; Biological: basiliximab; Drug: mycophenolate mofetil; Drug: tacrolimus

Interventions

Anti-thymocyte Globulin (Rabbit) BIOLOGICAL

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.

Also known as: Thymoglobulin®, ATG (Rabbit)

Thymoglobulin®+belatacept+MMF; Thymoglobulin®+tacrolimus+MMF

belatacept BIOLOGICAL

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.

Also known as: NULOJIX®

Basiliximab+20 weeks of tacrolimus+MMF + belatacept; Thymoglobulin®+belatacept+MMF

methylprednisolone DRUG

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.

Also known as: Medrol®

Basiliximab+20 weeks of tacrolimus+MMF + belatacept; Thymoglobulin®+belatacept+MMF; Thymoglobulin®+tacrolimus+MMF

basiliximab BIOLOGICAL

Basiliximab will be administered in two doses of 20 mg each.

Also known as: Simulect®

Basiliximab+20 weeks of tacrolimus+MMF + belatacept

mycophenolate mofetil DRUG

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.

Also known as: MMF, CellCept®, mycophenolate acid

Basiliximab+20 weeks of tacrolimus+MMF + belatacept; Thymoglobulin®+belatacept+MMF; Thymoglobulin®+tacrolimus+MMF

tacrolimus DRUG

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).

Also known as: Prograf®

Basiliximab+20 weeks of tacrolimus+MMF + belatacept; Thymoglobulin®+tacrolimus+MMF

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• 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.
• 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;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Clinical Trials in Organ Transplantation: collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 32558199 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Clinical Trials in Organ Transplantation (CTOT)

MeSH Terms

Interventions

Antilymphocyte Serum; thymoglobulin; Abatacept; Methylprednisolone; Basiliximab; Mycophenolic Acid; Tacrolimus

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Immunoconjugates; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Kenneth Newell, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

• Roslyn B. Mannon, M.D.

  University of Alabama at Birmingham

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 17, 2013
• Study Start: July 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 17, 2020
• Results First Posted: August 7, 2017

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After completion of the trial, within 24 months status post database lock.
• Access Criteria: Study Accession ID: SDY1434 Registration is available for the Immunology Database and Analysis Portal (ImmPort) at: https://www.immport.org/registration and submit a rationale for the purpose of requesting study data access. ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.

Locations

US (3)