Safety/Efficacy of Induction Agents With Tacrolimus, MMF, and Rapid Steroid Withdrawal in Renal Transplant Recipients (INTAC)

Phase 4, Randomized, Open-label, Comparative, Multicenter Study to Assess the Safety and Efficacy of Induction Agents, Alemtuzumab, Basiliximab or Rabbit Anti-thymocyte Globulin in Combination With Tacrolimus, MMF, and a Rapid Steroid Withdrawal in Renal Transplant Recipients

The purpose of this study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, mycophenolate mofetil (MMF) and a rapid steroid withdrawal.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: tacrolimus; Drug: mycophenolate mofetil; Drug: alemtuzumab; Drug: steroids; Drug: rabbit anti-thymocyte globulin; Drug: basiliximab

Detailed Description

A 2 arm (1 Active, 1 Active Control) study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, MMF and a rapid steroid withdrawal.

• Study Type: Interventional
• Enrollment (Actual): 501
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • California
    • Los Angeles, California, United States, 90057
    • Palo Alto, California, United States, 94304
    • San Diego, California, United States, 92123
    • San Francisco, California, United States, 94115
    • San Francisco, California, United States, 94143
  • Colorado
    • Denver, Colorado, United States, 80262
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
    • Washington, District of Columbia, United States, 20007
  • Florida
    • Miami, Florida, United States, 33136
    • Tampa, Florida, United States, 33066
  • Illinois
    • Chicago, Illinois, United States, 60611
    • Chicago, Illinois, United States, 60612
  • New Jersey
    • Livingston, New Jersey, United States, 07039
    • New Brunswick, New Jersey, United States, 08901
  • New York
    • Hawthorne, New York, United States, 10532
    • New York, New York, United States, 10032
    • New York, New York, United States, 10029
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Cincinnati, Ohio, United States, 45267
  • Oregon
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
    • Harrisburg, Pennsylvania, United States, 17105
  • South Carolina
    • Charleston, South Carolina, United States, 29425
  • Texas
    • San Antonio, Texas, United States, 78229
  • Utah
    • Salt Lake City, Utah, United States, 84132
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
    • Milwaukee, Wisconsin, United States, 53226

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recipient of a primary or re-transplanted deceased donor kidney or a primary or re-transplanted non-human leukocyte antigen (HLA) living donor kidney (ie., HLA identical or 0 antigen mismatch deceased donor kidneys are allowed).

Exclusion Criteria:

• Patient has previously received an organ transplant other than a kidney
• Patient receiving chronic steroid therapy at time of transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alemtuzumab High-Risk Patients; Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American	Drug: tacrolimus; oral; Other Names: Prograf, FK506; Drug: mycophenolate mofetil; oral; Other Names: CellCept; MMF; Drug: alemtuzumab; Intravenous (IV); Other Names: campath; Drug: steroids; IV and/or oral
Active Comparator: Conventional High-Risk Patients; Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American	Drug: tacrolimus; oral; Other Names: Prograf, FK506; Drug: mycophenolate mofetil; oral; Other Names: CellCept; MMF; Drug: steroids; IV and/or oral; Drug: rabbit anti-thymocyte globulin; IV; Other Names: Thymoglobulin
Experimental: Alemtuzumab Low- Risk Patients; Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American	Drug: tacrolimus; oral; Other Names: Prograf, FK506; Drug: mycophenolate mofetil; oral; Other Names: CellCept; MMF; Drug: alemtuzumab; Intravenous (IV); Other Names: campath; Drug: steroids; IV and/or oral
Active Comparator: Conventional Low-Risk Patients; Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American	Drug: tacrolimus; oral; Other Names: Prograf, FK506; Drug: mycophenolate mofetil; oral; Other Names: CellCept; MMF; Drug: steroids; IV and/or oral; Drug: basiliximab; IV; Other Names: simulect

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Incidence of Biopsy-confirmed Acute Rejection (BCAR) at 6 Months	A BCAR is a suspected new rejection w/in 6 mos. of skin closure, confirmed by Banff Grade ≥1A assigned by a pathologist. The Banff 97 classification system is used for interpreting histology of allograft biopsies, including Mild (1A/1B), Moderate (2A/2B) & Severe (3). Kaplan Meier analysis was used to estimate % of pts. w/event. Patients w/no event at time of scheduled visit or whose 1st event was after premature discontinuation of study drug/tacrolimus were censored on the scheduled day of a) assessment, b) of premature treatment discontinuation or c) last evaluation, whichever came 1st.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Patient Incidence of BCAR	Overall patient incidence of BCAR is defined as a suspected new rejection at any time following skin closure confirmed by a Banff Grade ≥ 1A as assigned by a local pathologist. Incidence is reported as the percentage of patients with BCAR. The Banff 97 scale is a classification system for interpreting histology of allograft biopsies. The grades range from Mild (1A & 1B) to Moderate (2A & 2B) to Severe (3). End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.	End of Study (36 months)
Efficacy Failure	Efficacy Failure is a composite measure of biopsy confirmed acute rejection, graft loss and death. Data is reported as the percentage of patients with Efficacy Failure. End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.	End of Study (36 months)
Clinically Treated Acute Rejection	Clinically treated acute rejection is defined as patient incidence of any rejection (suspected or otherwise) for which treatment was provided. Data is reported as the percentage of patients with Clinically Treated Acute Rejection. End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.	End of Study (36 months)
Time to First BCAR	Time to first BCAR is defined as the number of days from skin closure to the first episode of BCAR. End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.	End of Study (36 months)
Graft Survival at 12 Months	Graft survival is defined as no graft loss (re-transplant, return to dialysis for more than 30 days or death) with 12 months of skin closure. Kaplan Meier analysis was used to estimate percentage of patients with event. Patients with no event by the time of the scheduled visit or whose first event was after premature discontinuation of randomized study drug or tacrolimus were censored on the scheduled day of assessment, on the day of premature treatment discontinuation or last evaluation day, whichever came first.	12 months
Overall Graft Survival	Overall graft survival is defined as not having graft loss (re-transplant, return to dialysis for more than 30 consecutive days, or death) at any time following skin closure. Data is reported as the percentage of patients with Overall Graft Survival. End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.	End of Study (36 months)
Patient Survival at 12 Months	Patient survival is defined as not dead within 12 months after skin closure. Kaplan Meier analysis was used to estimate percentage of patients with event. Patients with no event by the time of the scheduled visit or whose first event was after premature discontinuation of randomized study drug or tacrolimus were censored on the scheduled day of assessment, on the day of premature treatment discontinuation or last evaluation day, whichever came first.	12 months
Overall Patient Survival	Overall patient survival is defined as not dead at any time following skin closure. Data is reported as the percentage of patients with Overall Patient Survival. End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.	End of Study (36 months)
Renal Function Abnormalities Based on Creatinine Clearance	Increases in creatinine clearance usually indicates an improvement. Change in creatinine clearance from month 1 was calculated. Change from 1 month is calculated by month 36 - month 1.	1 month and End of Study (36 months)
Renal Function Abnormalities Based on Serum Creatinine	Decrease in serum creatinine usually indicates an improvement. Change in creatinine clearance from month 1 was calculated. Change from 1 month is calculated by month 36 - month 1.	1 month and End of Study (36 months)

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Central Contact, Astellas Pharma Global Development

Publications and helpful links

General Publications

• Hanaway MJ, Woodle ES, Mulgaonkar S, Peddi VR, Kaufman DB, First MR, Croy R, Holman J; INTAC Study Group. Alemtuzumab induction in renal transplantation. N Engl J Med. 2011 May 19;364(20):1909-19. doi: 10.1056/NEJMoa1009546.

Helpful Links

• Link to Prescribing Information

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: June 7, 2005
• First Submitted That Met QC Criteria: June 7, 2005
• First Posted (Estimate): June 8, 2005

Study Record Updates

• Last Update Posted (Estimate): August 11, 2011
• Last Update Submitted That Met QC Criteria: August 9, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Immunosuppression; Renal Transplantation; Treatment Effectiveness; Treatment Efficacy; Grafting, Kidney; Transplantation, Kidney; Anti-rejection therapy; Transplantation, Renal; Therapy, antirejection
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Basiliximab; Thymoglobulin; Antilymphocyte Serum; Alemtuzumab
• Other Study ID Numbers: 20-04-003