A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation

NCT00455013 | Completed Phase 2 Results DMC

• 1 other identifier: IM103-034
• Study Type: interventional
• Target: 93
• Locations: 3 countries
• Sites: 17

Brief Summary

The purpose of this clinical research study is to learn if belatacept (BMS-224818) is expected to show acceptable rates of acute rejection (AR) in steroid-free belatacept-based immunosuppressive regiments compared to a similar steroid-free tacrolimus regimen. The long-term safety and tolerability of belatacept based regimens following long-term administration in subjects who have received a kidney transplant

Conditions

Disorder Related to Renal Transplantation

Keywords

Kidney transplant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population

  AR is clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) greater than or equal to 25% from baseline plus one or more of the following: unexplained decreased urine output; fever, graft tenderness; SCr that remained elevated 14 days post-transplantation and clinical suspicion of AR; other reason and participant treated for episode. Day 1=transplantation. Banff 97 working classification of kidney transplant pathology: Type I=tubulointerstitial AR without arteritis (IA: interstitial infiltration with \>25% of parenchyma affected and moderate tubulitis with \>4 mononuclear cells/tubular cross section; IB: \>10 mononuclear cells; Type II vascular AR with (IA) intimal arteritis (IIA=mild - moderate; IIB=severe; Type III=severe rejection with transmural arterial changes, necrosis of smooth muscle cells.

  Day 1 to Month 6 post-transplantation

Secondary Outcomes (19)

• Number of Participants With Acute Rejection of Transplant up to Month 12 Post Transplantation - Intent to Treat Population

  Day 1 to Month 12 post transplantation

• Number of Participants With Graft Loss or Death up to Month 6 and Month 12 Post Transplantation - Intent to Treat Population

  Day 1 to Month 6 and Month 12 post transplantation

• Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 6 - Intent to Treat Population

  Day 1 up to Month 6

• Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 12 - Intent to Treat Population

  Day 1 up to Month 12

• Number of Participants With Delayed Graft Function - Intent to Treat Population

  From Day 1 up to and including Day 8 post transplantation

Study Arms (3)

belatacept, mycophenolate mofetil (MMF)

EXPERIMENTAL

thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months; MMF 1g twice daily(bis in die, BID)

Drug: Thymoglobulin; Drug: Belatacept; Drug: Mycophenolate Mofetil (MMF)

belatacept, sirolimus

EXPERIMENTAL

thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months;sirolimus 5 mg/day on Day 1 (day of transplant)and continued through Day 2, dosing to be adjusted to keep pre-dose C0 levels at 7-12 ng/mL for first 6 months, followed by 5 - 10 ng/mL until 12 months.

Drug: Thymoglobulin; Drug: Belatacept; Drug: Sirolimus

tacrolimus, MMF

OTHER

(IMPs as comparator regimen)thymoglobulin 1.5mg/kg for 4 days; oral tacrolimus 0.1 mg/kg/day in 2 divided doses with initial targeted trough level of 8-12 ng/mL for Days 1 - 30 with dose reduction to achieve 12 hour trough target of 5-10 ng/mL for 12 months; MMF (mycophenolate mofetil) 1g BID.

Drug: Thymoglobulin; Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF)

Interventions

Thymoglobulin DRUG

Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours

belatacept, mycophenolate mofetil (MMF); belatacept, sirolimus; tacrolimus, MMF

Belatacept DRUG

Belatacept arms will receive i.v. belatacept (10 mg/kg) on Days 1 and 5, and then every other week through Month 3 (Weeks 2, 4, 6, 8, 10, and 12), and then every 4 weeks through Month 6 (Weeks 16, 20, and 24). After 6 months, subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial

Also known as: BMS-224818

belatacept, mycophenolate mofetil (MMF); belatacept, sirolimus

Sirolimus DRUG

Sirolimus will be initiated at 5 mg/day on Day 1 (day of transplant) and continued through Day 2. The dosing will be adjusted subsequently to keep pre-dose (C0) levels at 7 - 12 ng/mL for the first 6 months, followed by 5 - 10 ng/mL thereafter

belatacept, sirolimus

Tacrolimus DRUG

The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally up to and including week 52. Post week 52 subjects assigned to the tacrolimus arm will receive tacrolimus orally in accordance with local practice and the package insert until completion of the trial

tacrolimus, MMF

Mycophenolate Mofetil (MMF) DRUG

Administered orally in a capsule or solution formulation in 2 divided doses on a consistent schedule in relation to time of day and meals. The dose should be 1 g bid; however 1.5 g bid may be administered at the investigator's discretion until completion of the trial

belatacept, mycophenolate mofetil (MMF); tacrolimus, MMF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Living or deceased donor renal allograft
• Men and women, 18 to 70 years old
• Subjects who have received a de novo kidney transplant, who have completed the initial study treatment through Month 12, and are willing to sign informed consent will be eligible to continue into the long term extension phase

You may not qualify if:

• Pregnant or breastfeeding women
• Epstein Barr Virus (EBV) negative serology
• First time renal transplant with panel reactive antibody (PRA) ≥ 50% or retransplantation with PRA \> 30%
• Graft loss due to AR
• Positive T-cell or B-cell crossmatch
• Recipients/donors with HIV or hepatitis B/C
• Active tuberculosis (TB)
• Immunosuppressive therapy within 1 year of enrollment
• UNOS ECD organs will be excluded
• Body mass index (BMI) \> 35 kg/m²
• Subjects who have developed any malignancy (other than non-melanoma skin cancer) or other medical condition that, in the investigator's opinion, should not be treated with an experimental immunosuppressive drug like belatacept

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (17)

Ucsf

San Francisco, California, 94143, United States

Location

Denver Nephrology, Pc

Denver, Colorado, 80218, United States

Location

University Of Colorado Health Sciences Center

Denver, Colorado, 80262, United States

Location

Medical College Of Georgia

Augusta, Georgia, 30912, United States

Location

Northwestern University Feinberg School Of Medicine

Chicago, Illinois, 60611, United States

Location

Henry Ford Hospital

Detriot, Michigan, 48202, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

University Of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Local Institution

Bologna, Bologna, 40138, Italy

Location

Local Institution

Brescia, 25123, Italy

Location

Local Institution

Padua, 35128, Italy

Location

Local Institution

Roma, 00168, Italy

Location

Local Institution

Barcelona, 08907, Spain

Location

Local Institution

Seville, 41013, Spain

Location

MeSH Terms

Interventions

thymoglobulin; Abatacept; Sirolimus; Tacrolimus; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Limitations and Caveats

Main limitations of this study include: small size (small number of participants in each treatment arm), the open-label nature of the trial, its exploratory nature, and the high rate of switches from sirolimus to MMF in one of the belatacept groups.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2007
• First Posted: April 2, 2007
• Study Start: July 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: August 1, 2012
• Last Updated: June 9, 2014
• Results First Posted: November 21, 2013

Record last verified: 2014-05

Locations

ES (2); US (11); IT (4)