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Disorder Related to Renal TransplantationPhase 2NCT00455013

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

A Phase 2 study testing Thymoglobulin, Belatacept and Sirolimus in people with Disorder Related to Renal Transplantation, run by Bristol-Myers Squibb at 17 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Thymoglobulin, Belatacept and Sirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
17 sitesin 3 countries
Study dates
Jul 2007to Aug 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

United States11 sites

  • Albany Medical College

    Albany, New York, 12208

  • Medical College Of Georgia

    Augusta, Georgia, 30912

  • Carolinas Medical Center

    Charlotte, North Carolina, 28203

  • Northwestern University Feinberg School Of Medicine

    Chicago, Illinois, 60611

  • University Of Cincinnati

    Cincinnati, Ohio, 45267

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Denver Nephrology, Pc

    Denver, Colorado, 80218

  • University Of Colorado Health Sciences Center

    Denver, Colorado, 80262

  • Henry Ford Hospital

    Detriot, Michigan, 48202

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Ucsf

    San Francisco, California, 94143

Other trials in United States

Italy4 sites

  • Local Institution

    Bologna, Bologna, 40138

  • Local Institution

    Brescia, 25123

  • Local Institution

    Padova, 35128

  • Local Institution

    Roma, 00168

Other trials in Italy

Spain2 sites

  • Local Institution

    Barcelona, 08907

  • Local Institution

    Seville, 41013

Other trials in Spain

About this study

Official title: A Randomized, Open-Label, Multicenter, Parallel-Group Study of Belatacept (BMS-224818)-Based Corticosteroid-Free Regimens in Renal Transplant

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

Being tested
Thymoglobulin, Belatacept, Sirolimus, Tacrolimus, Mycophenolate Mofetil (MMF)
Keywords
Kidney transplant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ThymoglobulinDrug

    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

  • BelataceptDrug

    Also called BMS-224818

    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

  • SirolimusDrug

    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

  • TacrolimusDrug

    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

  • 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

Study groups in NCT00455013
Study groupRoleWhat they receive
belatacept, mycophenolate mofetil (MMF)Experimentalthymoglobulin 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)
Receives: Drug: Thymoglobulin; Drug: Belatacept; Drug: Mycophenolate Mofetil (MMF)
belatacept, sirolimusExperimentalthymoglobulin 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.
Receives: Drug: Thymoglobulin; Drug: Belatacept; Drug: Sirolimus
tacrolimus, MMFOther(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.
Receives: Drug: Thymoglobulin; Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Day 1 to Month 6 post-transplantation

Secondary outcomes (19)

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

    AR defined as a 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) >= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.

    Measured: Day 1 to Month 12 post transplantation

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

    Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for >= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.

    Measured: Day 1 to Month 6 and Month 12 post transplantation

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

    Participants with graft loss or death prior to Month 6 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.

    Measured: Day 1 up to Month 6

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

    Subjects with graft loss or death prior to Month 12 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.

    Measured: Day 1 up to Month 12

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

    Delayed graft function (DGF) is defined as participant requiring dialysis within the first week (Day 1-8) post transplantation. Participants losing their graft less than 48 hours post transplant and receiving chronic dialysis were not considered as having DGF. Day 1 was day of transplantation. Intent to treat population defined as all participants randomized and transplanted

    Measured: From Day 1 up to and including Day 8 post transplantation

  6. Number of Participants With New Onset Diabetes Mellitus From Baseline to Month 12 Post Transplantation - Intent to Treat Population

    Baseline defined as day before transplantation. A participant who did not have diabetes prior to randomization and received an antidiabetic medication for a duration of at least 30 days or a participant who meets the following criteria and did not have diabetes prior to randomization: Symptoms of diabetes plus casual plasma glucose (PG) concentration ≥ 200 mg/dL (11.1 mmol/L); or fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L); or 2-hour PG ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test and a confirmatory laboratory test based on measurements of venous PG must have been done on another day in the absence of unequivocal hyperglycemia accompanied by acute metabolic decompensation.

    Intent to treat population included all participants randomized and transplanted.

    Measured: Baseline to Month 12

  7. Number of Participants Who Used Anti-hypertension Medications at Baseline and at 12 Months Post Transplantation - Intent to Treat Population

    Baseline was defined as day prior to transplantation. Number of anti-hypertension medications taken were categorized from 1 to 6 and greater than (>)6. Intent to treat population included all participants randomized and transplanted.

    Measured: Baseline and Month 12

  8. Mean Systolic, Diastolic and Arterial Blood Pressure at Baseline and Month 12 - Intent to Treat Population

    Systolic, diastolic and mean arterial blood pressures were measured in millimeters of mercury (mm Hg). Baseline was defined as value obtained before transplantation. Intent to treat population included all participants randomized and transplanted.

    Measured: Baseline and 12 months post transplantation

  9. Number of Participants Using Antihyperlipidemic Medications at Month 12 - Intent to Treat Population

    Participants using > = 1 antihyperlipidemic medication at Month 12.

    Measured: Month 12

  10. Mean Change From Baseline (BL) to Month 12 Post Transplantation in Lipid Values - Intent to Treat Population

    Baseline (BL) was value obtained day prior to transplantation. Lipid values measured in milligrams/deciliter (mg/dL) included: high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL cholesterol (non-HDL-C), total cholesterol (TC), triglycerides. Intent to treat population included all participants randomized and transplanted.

    Measured: Baseline to Month 12

  11. Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Month 3, Month 6 and Month 12 Post Transplantation - Intent to Treat Population

    Blood urea nitrogen (BUN) in mg/dL; Albumin (Alb) in g/dL;Serum creatinine (SCr) in mg/dL; Age in years. Glomerular filtration rate (GFR) was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if participant was female] x [1.180 if participant was black] x [BUN]^(-0.170) x [Alb]^(+0.318). Intent to Treat (ITT) population is defined as all participants randomized and transplanted.

    Measured: Months 3, 6 and 12 post transplantation

  12. Number of Corticosteroid-free Participants at 6 and 12 Months Post Transplantation - Intent to Treat Population

    Participants were said to be corticosteroid-free at Month 6 if they were not receiving corticosteroids for greater than (>) 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for > 7 days during Days 337 through 392. Intent to treat population included all randomized and transplanted participants.

    Measured: Day 1 through Month 12

  13. Number of Participants Who Were Corticosteroid-free at Months 6 and 12 and Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 6 and 12 Post Transplantation - Intent to Treat Population

    Participants were said to be CNI-free at Month 6 or 12 if they were not receiving a CNI during Day 141 to Day 196, or Day 337 to Day 392. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor. Participants were corticosteroid-free (CS-free) at Month 6 if they were not receiving corticosteroids for > 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for > 7 days during Days 337 through 392. Day 1 was day of transplantation. Intent to treat population included all randomized and transplanted participants.

    Measured: Day 1 to Month 12 post transplantation

  14. Number of Participants With Acute Rejection of Transplant up to End of Month 48 Post Transplantation - Intent to Treat Population in Long Term Extension

    AR defined as a 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) >= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.

    Measured: End of Month 12 to end of Month 48 Post Transplantation

  15. Number of Participants With Graft Loss or Death at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension

    Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for >= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.

    Measured: End of Month 12 to end of Long Term Extension (Year 4)

  16. Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Months 24, 36 and 48 Post Transplantation - Intent to Treat Population in Long Term Extension

    GFR was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if participant was female] x [1.180 if participant was black] x [BUN]^(-0.170) x [Alb]^(+0.318). Age in years, Alb = Albumin in g/dL; SCr = in mg/dL; BUN =Blood urea nitrogen in mg/dL. Intent to Treat population is defined as all participants randomized and transplanted.

    Measured: Months 24, 36 and 48 post transplantation

  17. Number of Corticosteroid-free Participants at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension

    In the LTE, a participant was considered corticosteroid-free if they were not receiving corticosteroids for >7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively.

    Measured: End of Month 12 to end of Long Term Extension (Year 4)

  18. Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension

    Participants were considered corticosteroid-free at Months 24, 36, and 48 if they were not receiving corticosteroids for >7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants were considered CNI-free at Months 24, 36, and 48 if they were not receiving CNI during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor.

    Measured: Months 24, 36, 48

  19. Number of Participants Who Switched Between MMF and Sirolimus During Long Term Extension up to Study Completion

    Long Term extension was the period from the end of Month 12 to the end of Month 48 post transplantation and the completion of the study 31 July 2012. At any time in the study, participants who were unable to tolerate MMF in the Bela-MMF and Tac-MMF groups could discontinue (DC) MMF and switch to sirolimus and remain in the study and those in the Bela-Siro group who were unable to tolerate sirolimus could DC sirolimus and switch to MMF and remain in the study. Study completion=data base (DB) lock.

    Measured: End of Month 12 to end of Study (Month 48)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2007 (estimated)
  2. Study startJul 2007
  3. Primary completionOct 2008
  4. Study completionAug 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00455013
Sponsor's protocol ID
IM103-034
Status last verified
May 2014
First submitted
30 Mar 2007
Last updated
9 Jun 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thymoglobulin, Belatacept and Sirolimus in people with Disorder Related to Renal Transplantation, run by Bristol-Myers Squibb at 17 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population (time frame: Day 1 to Month 6 post-transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00455013.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2014.

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