Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation

NCT ID: NCT01790594

Last Updated: 2021-07-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2016-08-31

Brief Summary

The purpose of this study is to find out if the drug NULOJIX® (belatacept) will minimize the amount of other anti-rejection medications necessary and thereby reduce the long-term side effects caused by the other medications. The researchers also want to learn more about the safety of this treatment and long term health of transplanted pancreases and kidneys.

Detailed Description

Transplant recipients have to take anti-rejection medications to prevent their immune systems (the body's natural defense system against illness) from rejecting their new organs. Most patients who receive a transplanted organ must take these anti-rejection medications for the rest of their lives, or for as long as the transplanted organ continues to work. Taking standard anti-rejection medications for a long time can cause serious side effects, including pancreas and kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but could lessen the amount of anti-rejection medications that are taken long term.

Conditions

Simultaneous Kidney and Pancreas Transplantation

Study Design

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

Study Groups

Immunosuppression without Belatacept

• Induction: 5 day course of methylprednisolone or equivalent;
• Induction: Anti-thymocyte Globulin (Rabbit);
• Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter.
• Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).

Group Type: ACTIVE_COMPARATOR

methylprednisolone

Intervention Type: DRUG

Anti-thymocyte Globulin (Rabbit)

Intervention Type: BIOLOGICAL

Tacrolimus

Intervention Type: DRUG

There may be an opportunity to withdraw tacrolimus at week 40

Mycophenolate mofetil

Intervention Type: DRUG

Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). 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.

Immunosuppression Including Belatacept

• Induction: 5 day course of methylprednisolone or equivalent;
• Induction: Anti-thymocyte Globulin (Rabbit);
• Maintenance Immunosuppression: Belatacept
• Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below.
• Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: BIOLOGICAL

The first dose of belatacept will be administered approximately 24-48 hours after the last dose of Anti-Thymocyte Globulin (Rabbit).

methylprednisolone

Intervention Type: DRUG

Anti-thymocyte Globulin (Rabbit)

Intervention Type: BIOLOGICAL

Tacrolimus

Intervention Type: DRUG

There may be an opportunity to withdraw tacrolimus at week 40

Mycophenolate mofetil

Intervention Type: DRUG

Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). 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.

Interventions

Belatacept

The first dose of belatacept will be administered approximately 24-48 hours after the last dose of Anti-Thymocyte Globulin (Rabbit).

Intervention Type: BIOLOGICAL

methylprednisolone

Intervention Type: DRUG

Anti-thymocyte Globulin (Rabbit)

Intervention Type: BIOLOGICAL

Tacrolimus

There may be an opportunity to withdraw tacrolimus at week 40

Intervention Type: DRUG

Mycophenolate mofetil

Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). 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.

Intervention Type: DRUG

Other Intervention Names

NULOJIX; Medrol; Thymoglobulin; ATG (Rabbit); Prograf; MMF, mycophenolate sodium, CellCept

Eligibility Criteria

Inclusion Criteria

• Ability to understand and provide written informed consent;
• Candidate for a primary simultaneous kidney and pancreas allograft with random c-peptide <0.3 ng/mL;
• No known contraindications to study therapy using NULOJIX® (belatacept);
• Female subjects 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 study completion;
• No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
• Negative crossmatch, actual or virtual, or a Panel Reactive Antibodies (PRA) of 0% on historic and admission sera, as determined by each participating study center;
• A documented negative Tuberculosis (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 transplantation other than a kidney and pancreas;
• Recipient of previous organ transplant;
• Epstein-Barr Virus (EBV) sero-negative recipients or recipients whose EBV serostatus is unknown prior to the time of transplantation;
• Individuals infected by the hepatitis B or C viruses or HIV;
• Individuals who have required treatment with systemic prednisone or other immunosuppressive drugs within 1 year prior to transplant;
• 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: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trials in Organ Transplantation

NETWORK

Sponsor Role: collaborator

Rho Federal Systems Division, Inc.

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

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: PRINCIPAL_INVESTIGATOR

Emory University

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California San Francisco Medical Center

San Francisco, California, United States

Emory University

Atlanta, Georgia, United States

Indiana University Hospital

Indianapolis, Indiana, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Stock PG, Mannon RB, Armstrong B, Watson N, Ikle D, Robien MA, Morrison Y, Odorico J, Fridell J, Mehta AK, Newell KA. Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial. Am J Transplant. 2020 Jun;20(6):1668-1678. doi: 10.1111/ajt.15817. Epub 2020 Mar 8.

Reference Type: RESULT

PMID: 32039559 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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

National Institute of Allergy and Infectious Diseases (NIAID) website

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

Division of Allergy, Immunology, and Transplantation (DAIT) website

https://www.ctotstudies.org/

Clinical Trials in Organ Transplantation (CTOT) website

Other Identifiers

U01AI084150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIAID CRMS ID#: 20117

Identifier Type: OTHER

Identifier Source: secondary_id

SDY1433

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT CTOT-15

Identifier Type: -

Identifier Source: org_study_id