Belatacept Conversion Trial in Renal TransplantationRevised Protocol 02 incorporating Amendments 03 (version 1.0 dated 18-Sep-07) and 04 (version 3.0 dated 12-Oct-07)

• Conditions: Subjects who received a kidney transplant

• Registration Number: EUCTR2005-005238-11-DE
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02-20
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

1) The subject is willing to provide signed written informed consent
2) Subjects must be a recipient of a renal allograft from a living donor or a deceased donor at least 6 months, but not longer than 36 months, prior to enrollment
3) Subjects must be receiving a CNI-based (CsA [any formulation] or TAC) immunosuppressive regimen
4) The dose of CNI must have been stable over the month prior to randomization
a) For subjects receiving CsA, trough serum concentration at the time of enrollment must be 100-250 ng/mL (based on screening/baseline local laboratory results)
b) For subjects receiving TAC, trough serum concentration at the time of enrollment must be 5-10 ng/mL (based on screening/baseline local laboratory results)
5) Subjects must be receiving adjunctive background maintenance immunosuppression with MMF, MPA, SRL, or AZA
a) Subjects receiving MMF must have received a minimum total daily dose of 1.5 g for the month prior to randomization (up to 3 missed doses are acceptable provided doses were not missed due to drug intolerance)
b) Subjects receiving MPA must have received a minimum total daily dose of 1080 mg for the month prior to randomization (up to 3 missed doses are acceptable provided doses were not missed due to drug intolerance)
c) Subjects receiving AZA must have received a minimum daily dose of 50 mg for the month prior to randomization (up to 3 missed doses are acceptable provided doses were not missed due to drug intolerance)
d) Subjects receiving SRL must have a trough serum concentration at the time of enrollment of 5-15 ng/mL (based on screening/baseline local laboratory results)
6) If subjects are receiving concomitant corticosteroids (steroid use is not required), the dose of corticosteroid must have been stable over the month prior to randomization with no anticipated dose alteration in the next 12 months unless a change in the medical condition warrants adjustment.
7) Subjects must have a calculated GFR = 35 and = 75 mL/min/1.73 m2 (MDRD formula) at the time of enrollment (based on screening/baseline central laboratory results)
8) Men and women, ages 18 years and older, inclusive
9) WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized.

Inclusion criteria for participation to Protocol Amendment 4 - Long-Term Extension:
11) Subjects must be willing to participate and provide signed, written informed consent for this long-term extension phase.
12) Subjects must have completed 1 year in the IM103010 study (through Month 12) aand remained on study treatment
13) Subjects must be willing and able to continue therapy with MMF, MPA, sirolimus (SRL) or azathioprine (AZA). If a subject is unable to tolerate minimum therapeutic doses of their current adjunctive background maintenance immunosuppression, another adjuvant agent may be substituted.
14) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
15) Subjects originally assigned to the CNI treatment group must be willing and able to continue therapy with CsA or TAC

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) ye

Exclusion Criteria

1) WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study medication. It should be noted that according to the US product information for mycophenolate mofetil (CellCept®) and mycophenolic acid (Myfortic®), two reliable forms of contraception be used simultaneously unless abstinence is the chosen method”
2) WOCBP using a prohibited contraceptive method
3) Women who are pregnant or breastfeeding
4) Women with a positive pregnancy test on enrollment or prior to study drug administration
5) Subjects with underlying renal disease of:
a) Primary focal segmental glomerulosclerosis
b) Type I or II membranoproliferative glomerulonephritis
c) Hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura syndrome

Subjects :
6) expected to undergo weaning of immunosuppressive therapy during the period of the study
8) with previous graft loss due to acute rejection (AR)
9) whose SCr at enrollment is over 30% higher than 3 months (± 4 weeks) prior to randomization
10) with an episode of AR in the last 3 months. Subjects who have had an episode of AR are required to have had clinical resolution for at least 3 months prior to randomization
11) who have had a Banff 97 Grade IIA or greater AR (or equivalent), steroid-resistant AR or have received lymphocyte-depleting agents, plasmapheresis, or rituximab for the treatment of AR since transplantation of current allograft
12) who have experienced more than 1 episode of rejection of the current allograft
13) with a biopsy of the current allograft staining C4d positive. Neither a biopsy nor C4d staining is required for entry into the study
14) who have experienced complications of anastomotic stenosis or stricture (vascular or ureteral)
15) who had a positive T-cell or B-cell crossmatch
16) who have documented BK virus (polyoma virus) nephropathy (biopsy is not required for enrollment)
17) who have documented evidence of recurrence of the primary cause of end-stage renal disease (ESRD) in their current or in a past renal allograft
18) with multiple solid organ or cell transplants
19) who received paired kidneys (dual or en bloc kidney transplants)
20) who are known hepatitis C antibody-positive or PCR-positive for hepatitis C (neither hepatitis C antibody or PCR for hepatitis C testing is required for study entry)
21) who are known hepatitis B surface antigen-positive or PCR-positive for
hepatitis B (neither hepatitis B surface antigen or PCR for hepatitis B testing is required for study entry)
22) with known HIV infection. HIV testing is not required for study entry
23) with a chest radiograph (posterior-anterior and lateral views) consistent with an acute lung parenchymal process, malignancy, or active tuberculosis. Subjects must have a chest radiograph within 2 months prior to randomization
24) with any significant infection

Medical History and Concurrent Diseases
25) Subjects whose life expectancy is severely limited by disease state or other underlying medical condition
26) Subjects with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years
27) Subjects with a history of substance abuse (drug or alcohol) within the past 5 years, or psychotic disorders that are not compatible with adequate study follow-up

Physical and Laboratory Test Findings
28) Subjects with laboratory values that meet the following criteria:
Urine Assay:
• Proteinuria >

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified