Optimization of NULOJIX® (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Clinical Trials in Organ Transplantation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01790594
First received: February 11, 2013
Last updated: August 6, 2013
Last verified: August 2013
  Purpose

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 lesson the amount of antirejection medications you are taking long term.

The purpose of this study is to find out if the drug NULOJIX® (belatacept) will minimize the amount of other antirejection 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.


Condition Intervention Phase
Pancreas and Kidney Transplant
Biological: Belatacept
Drug: methylprednisolone
Biological: Anti-thymocyte Globulin
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimization of NULOJIX® (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Mean glomerular filtration rate (GFR) [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Calculated for each treatment group using the Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI)


Secondary Outcome Measures:
  • Measures of Renal Function and Injury [ Time Frame: 52, 104, 156 weeks ] [ Designated as safety issue: Yes ]
    • Proportion of subjects with eGFR < 60 mL/min/1.73 m2 measured by CKD-EPI
    • Change in CKD stages from baseline
    • Proportion of subjects with defined CKD stage 4 or 5
    • Mean calculated eGFR using MDRD 4 variable model
    • eGFR by CKD-EPI over time based on serum creatinine
    • Incidence of successful discontinuation of tacrolimus in recipients randomized to the investigational arm
    • Incidence of delayed graft function
    • An increase of one or more grades of CAN/IFTA when comparing the implantation and subsequent protocol biopsies
    • Incidence of CAN/IFTA grade 1, 2, 3

  • Measures of Cardiovascular and Metabolic Parameters [ Time Frame: baseline, days 28, 84, and weeks 28, 36, 52, 72, 104 and 156 ] [ Designated as safety issue: Yes ]
    • HbA1c fasting Blood Sugar (FBS)
    • standardized blood pressure measurement and use of anti-hypertensive medications
    • fasting lipid profile
    • the use of lipid lowering medications

  • Incidence and Severity of Rejection and Anti-Donor Reactivity [ Time Frame: 52 weeks, post-transplant ] [ Designated as safety issue: Yes ]
    • Incidence and severity of acute cellular rejection (also measured at weeks 104 and 156)
    • Severity of first and highest grade of acute cellular rejection in the renal and pancreas biopsies
    • Incidence of humoral rejection in the renal and pancreas biopsies
    • Prevalence of de novo anti-donor antibodies and anti-HLA antibodies
    • Type of treatment of rejection.

  • Safety Outcome Measures [ Time Frame: 52, 104, 156 weeks ] [ Designated as safety issue: Yes ]
    • Incidence of death
    • Graft loss
    • Undetectable c-peptide
    • All adverse events


Estimated Enrollment: 60
Study Start Date: February 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).
Drug: methylprednisolone
Other Name: Medrol
Biological: Anti-thymocyte Globulin
Other Name: Thymoglobulin
Drug: Tacrolimus
There may be an opportunity to withdraw tacrolimus at week 40
Other Name: Prograf
Drug: Mycophenolate mofetil
Mycophenolate mofetil will be administered at a target dose of 1000 mg PO 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.
Other Name: MMF, mycophenolate sodium, CellCept
Experimental: 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).
Biological: Belatacept
The first dose of belatacept will be administered approximately 24-48 hours after the last dose of Anti-Thymocyte Globulin.
Other Name: NULOJIX
Drug: methylprednisolone
Other Name: Medrol
Biological: Anti-thymocyte Globulin
Other Name: Thymoglobulin
Drug: Tacrolimus
There may be an opportunity to withdraw tacrolimus at week 40
Other Name: Prograf
Drug: Mycophenolate mofetil
Mycophenolate mofetil will be administered at a target dose of 1000 mg PO 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.
Other Name: MMF, mycophenolate sodium, CellCept

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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 transplantation other than a kidney and pancreas
  • Recipient of previous organ transplant;
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01790594

Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Contact: Deana Mays    205-934-0035    dmays@uab.edu   
Principal Investigator: Roslyn B Mannon, MD         
United States, California
University of California Recruiting
San Francisco, California, United States, 94143-0780
Contact: Laurie Carlson, MSRN    415-353-8892    Laurie.Carlson@ucsfmedctr.org   
Principal Investigator: Peter G Stock, MD, PhD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Sue Mead    404-712-1787    Beth.Begley@emoryhealthcare.org   
Principal Investigator: Kenneth Newell, MD, PhD         
Sponsors and Collaborators
Clinical Trials in Organ Transplantation
Investigators
Principal Investigator: Kenneth Newell, MD, PhD Emory University
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01790594     History of Changes
Other Study ID Numbers: DAIT CTOT-15
Study First Received: February 11, 2013
Last Updated: August 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Antilymphocyte Serum
Mycophenolate mofetil
Tacrolimus
Abatacept
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Pancrelipase
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on July 20, 2014