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

NCT ID: NCT01436305

Last Updated: 2017-09-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2015-04-30

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.

Detailed Description

Dialysis or kidney transplant are the two ways to treat kidney failure. 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 undergo a kidney transplant must take these anti-rejection medications for the rest of their lives. Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but don't damage the kidney.

Conditions

Kidney Transplantation; Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tac maintenance

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)

Group Type: ACTIVE_COMPARATOR

tacrolimus

Intervention Type: DRUG

maintenance

methylprednisolone

Intervention Type: DRUG

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

Alemtuzumab

Intervention Type: 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.

MMF

Intervention Type: 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.

Belatacept maintenance

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)

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: BIOLOGICAL

maintenance

methylprednisolone

Intervention Type: DRUG

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

Alemtuzumab

Intervention Type: 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.

MMF

Intervention Type: 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.

Basiliximab induction/Short-term Tac

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)

Group Type: EXPERIMENTAL

Short-term Tac

Intervention Type: DRUG

Short-term (3 months)

Belatacept

Intervention Type: BIOLOGICAL

maintenance

methylprednisolone

Intervention Type: DRUG

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

MMF

Intervention Type: 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.

Basiliximab

Intervention Type: 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\[s\])

Interventions

Short-term Tac

Short-term (3 months)

Intervention Type: DRUG

tacrolimus

maintenance

Intervention Type: DRUG

Belatacept

maintenance

Intervention Type: BIOLOGICAL

methylprednisolone

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

Intervention Type: DRUG

Alemtuzumab

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.

Intervention Type: DRUG

MMF

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.

Intervention Type: DRUG

Basiliximab

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\[s\])

Intervention Type: BIOLOGICAL

Other Intervention Names

Campath®; mycophenolate mofetil; CellCept®; Simulect®; tacrolimus; Prograf®; Prograf®; Nulojix®; MEDROL®

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trials in Organ Transplantation

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kenneth Newell, MD, PhD

Role: STUDY_CHAIR

Emory University

Christian P. Larsen, MD, DPhil

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

University of Alabama

Birmingham, Alabama, United States

University of California San Francisco

San Francisco, California, United States

Emory University

Atlanta, Georgia, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 28556519 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

https://www.ctotstudies.org/index.htm

Clinical Trials in Organ Transplantation (CTOT) website

Other Identifiers

DAIT CTOT-10

Identifier Type: -

Identifier Source: org_study_id