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

This study has been terminated.
(Secondary to safety concerns plus change in Campath® (alemtuzumab) availability.)
Sponsor:
Collaborator:
Clinical Trials in Organ Transplantation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01436305
First received: September 13, 2011
Last updated: April 20, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Kidney Transplantation
Renal Transplantation
Drug: Alemtuzumab
Drug: MMF
Biological: Basiliximab
Drug: Short-term Tac
Drug: tacrolimus
Biological: Belatacept
Drug: methylprednisolone
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 Avoiding CNI and Steroids in Renal Transplantation (CTOT-10)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The incidence of all adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Enrollment to Year 5 ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: September 2011
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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)

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.
Other Name: Campath®
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.

Other Names:
  • mycophenolate mofetil
  • CellCept®
Drug: tacrolimus
maintenance
Other Name: Prograf®
Drug: methylprednisolone
All study treatment groups: administration started on the day of transplant and tapered over a 4 day course.
Other Name: MEDROL®
Experimental: 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)

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.
Other Name: Campath®
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.

Other Names:
  • mycophenolate mofetil
  • CellCept®
Biological: Belatacept
maintenance
Other Name: Nulojix®
Drug: methylprednisolone
All study treatment groups: administration started on the day of transplant and tapered over a 4 day course.
Other Name: MEDROL®
Experimental: 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)

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.

Other Names:
  • mycophenolate mofetil
  • CellCept®
Biological: 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])
Other Name: Simulect®
Drug: Short-term Tac
Short-term (3 months)
Other Names:
  • tacrolimus
  • Prograf®
Biological: Belatacept
maintenance
Other Name: Nulojix®
Drug: methylprednisolone
All study treatment groups: administration started on the day of transplant and tapered over a 4 day course.
Other Name: MEDROL®

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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ECD or 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.
  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: NCT01436305

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Trials in Organ Transplantation
Investigators
Study Chair: Ken Newell, MD, PhD Emory University
Principal Investigator: Christian Larsen, MD, DPhil Emory University
  More Information

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01436305     History of Changes
Other Study ID Numbers: DAIT CTOT-10 
Study First Received: September 13, 2011
Last Updated: April 20, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
immunosuppressive (IS) regimens
long-term graft function
CNI (calcineurin Inhibitor )-free IS regimen
CNI (calcineurin Inhibitor ) IS regimen
corticosteroids

Additional relevant MeSH terms:
Alemtuzumab
Basiliximab
Calcineurin Inhibitors
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Mycophenolate mofetil
Mycophenolic Acid
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Tacrolimus
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2016