Optimization of NULOJIX® Usage As A Means of Avoiding CNI and Steroids in Renal Transplantation

NCT01436305 | Terminated Phase 2 Results DMC

• 1 other identifier: DAIT CTOT-10
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study was to assess whether a new drug, Nulojix® (belatacept), would minimize serious long term side effects associated with anti-rejection medications while still protecting the new kidney from damage. The researchers also wanted to learn more about the safety of this treatment and long term health of the transplanted kidney.

Conditions

Kidney Transplantation; Renal Transplantation

Keywords

immunosuppressive (IS) regimens; long-term graft function; CNI (calcineurin Inhibitor )-free IS regimen; CNI (calcineurin Inhibitor ) IS regimen; corticosteroids

Outcome Measures

Primary Outcomes (1)

• Mean Glomerular Filtration Rate (GFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52

  GFR 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.

  Week 52

Secondary Outcomes (29)

• Count of Participants With Biopsy Proven Acute Rejection at Any Time Post-Transplant

  Transplantation through last study visit (up to week 156)

• Count of Participants With Estimated Glomerular Filtration Rate (GFR) < 60 mL/Min/1.73 m^2 by CKD EPI

  Week 52, Week 104, and Week 156

• Count of Participants by Chronic Kidney Disease (CKD) Stage Post-Transplant

  Week 52, Week 104, and Week 156

• Count of Participants With CKD Stage 4 or 5

  Week 52, Week 104, and Week 156

• Mean Calculated eGFR Using MDRD 4 Variable Model

  Week 52, Week 104, and Week 156

Study Arms (3)

Tac maintenance

ACTIVE COMPARATOR

Group 1 Study Therapy Regimen:Induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). Campath® (alemtuzumab); long-term Prograf® (tacrolimus), or equivalent ; CellCept® (mycophenolate mofetil- MMF), or equivalent , and 4 day course of MEDROL® (methylprednisolone)

Drug: Alemtuzumab; Drug: MMF; Drug: tacrolimus; Drug: methylprednisolone

Belatacept maintenance

EXPERIMENTAL

Group 2 Study Therapy Regimen: Induction with alemtuzumab and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF). Campath® (alemtuzumab); Nulojix® (belatacept); CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL®(Methylprednisolone)

Drug: Alemtuzumab; Drug: MMF; Biological: Belatacept; Drug: methylprednisolone

Basiliximab induction/Short-term Tac

EXPERIMENTAL

Short term = 3 months Group 3 Study Therapy Regimen: Induction with 2 doses of basiliximab and tacrolimus for 84 days and maintenance with Nulojix® (belatacept) and mycophenolate mofetil (MMF). Simulect® (basiliximab); Nulojix® (belatacept); short-term course of Prograf® (tacrolimus), or equivalent; CellCept® (mycophenolate mofetil- MMF), or equivalent, and 4 day course of MEDROL® (methylprednisolone)

Drug: MMF; Biological: Basiliximab; Drug: Short-term Tac; Biological: Belatacept; Drug: methylprednisolone

Interventions

Alemtuzumab DRUG

Induction therapy. Group 1 and 2 study therapy regimens include induction with alemtuzumab, administered as a single intravenous dose intra-operatively over a period of 2 hours.

Also known as: Campath®

Belatacept maintenance; Tac maintenance

MMF DRUG

All treatment groups (e.g., Group 1, 2 and 3): Administered at a target dose of 1000 mg by mouth twice daily beginning on the day of surgery or post operative day 1 and adjusted as clinically warranted. Note: Myfortic® (mycophenolate sodium) may be used as a replacement for MMF, at a dose of 720 mg taken by mouth twice daily.

Also known as: mycophenolate mofetil, CellCept®

Basiliximab induction/Short-term Tac; Belatacept maintenance; Tac maintenance

Basiliximab BIOLOGICAL

Induction therapy. Group 3 study therapy regimen includes induction with basiliximab, administered in two doses: 1 dose administered within 2 hours prior to transplantation surgery and the 2nd dose 4 days after transplantation (unless held due to contraindication\[s\])

Also known as: Simulect®

Basiliximab induction/Short-term Tac

Short-term Tac DRUG

Short-term (3 months)

Also known as: tacrolimus, Prograf®

Basiliximab induction/Short-term Tac

tacrolimus DRUG

maintenance

Also known as: Prograf®

Tac maintenance

Belatacept BIOLOGICAL

maintenance

Also known as: Nulojix®

Basiliximab induction/Short-term Tac; Belatacept maintenance

methylprednisolone DRUG

All study treatment groups: administration started on the day of transplant and tapered over a 4 day course.

Also known as: MEDROL®

Basiliximab induction/Short-term Tac; Belatacept maintenance; Tac maintenance

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 a 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;
• Female and male participants with reproductive potential must agree to use FDA approved methods of birth control during participation in the study and for 4 months following completion of the study;
• Flow-based PRA within last 12 months (in absence of a sensitizing event) of \< 30% as determined by each participating study center. If the subject experienced a sensitizing event after the PRA test date, then the PRA must be repeated and confirmed \<30%;
• Negative crossmatch or a PRA of 0% on historic and admission sera as determined by each participating study center.
• A documented negative TB test within the 12 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;
• EBV sero-negative (or unknown) recipients;
• Active infection including hepatitis B, hepatitis C, or 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;
• HLA identical living donors;
• Individuals at significant risk of early recurrence of the primary renal disease including FSGS and 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;
• Individuals previously treated with NULOJIX® (belatacept);
• 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.

Sponsors & Collaborators

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

Study Sites (3)

University of Alabama

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)

• Newell KA, Mehta AK, Larsen CP, Stock PG, Farris AB, Mehta SG, Ikle D, Armstrong B, Morrison Y, Bridges N, Robien M, Mannon RB. Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. Am J Transplant. 2017 Oct;17(10):2712-2719. doi: 10.1111/ajt.14377. Epub 2017 Jul 3.

  PMID: 28556519 RESULT

Related Links

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

MeSH Terms

Interventions

Alemtuzumab; Mycophenolic Acid; Basiliximab; Tacrolimus; Abatacept; Methylprednisolone

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Enrollment of 210 participants was planned, but study was stopped after 19 participants enrolled due to safety concerns and change in alemtuzumab availability. Enrolled participants continued follow-up after enrollment ended.

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

  STUDY CHAIR

• Christian P. Larsen, MD, DPhil

  Emory University

  PRINCIPAL INVESTIGATOR

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: September 13, 2011
• First Posted: September 19, 2011
• Study Start: September 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: September 27, 2017
• Results First Posted: August 30, 2017

Record last verified: 2017-08

Locations

US (3)