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Renal TransplantPhase 2BESTTNCT00346151

Belatacept to Prevent Organ Rejection in Kidney Transplant Patients

A Phase 2 study testing Belatacept, Sirolimus and Anti-thymocyte globulin in people with Renal Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Belatacept is an experimental medication shown in clinical trials to have immune system suppression properties in people who have had renal (e.g., kidney) transplants. This study will determine whether a combination of anti-rejection drugs, including belatacept, can prevent the rejection of a first-time, non-human… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Renal Transplant
What is being tested?
Belatacept, Sirolimus and Anti-thymocyte globulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
2 sitesUnited States
Study dates
Dec 2006to Feb 2010
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Receiving first renal (e.g., kidney) transplant
  • Transplant is from a non-HLA-identical living donor
  • Willing to use acceptable forms of contraception

Who cannot join

  • Positive for anti-human globulin (AHG) or T-cell cross-match with the donor
  • Receiving multiple-organ transplant
  • History of cancer within the 5 years prior to study entry. Patients who have certain nonmelanoma skin cancers are not excluded
  • Human immunodeficiency virus (HIV) infected
  • Hepatitis B (HBV) or C (HCV) virus infected
  • Other active infections
  • Active tuberculosis (TB) infection within the 3 years prior to study entry
  • Pregnancy or breastfeeding

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Emory University

    Atlanta, Georgia, 30322

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: The Safety and Efficacy of Belatacept, Antithymocyte Globulin, and Sirolimus in Recipients of Non-HLA-identical Living-donor Renal Transplants (ITN023ST)

Belatacept is an experimental medication shown in clinical trials to have immune system suppression properties in people who have had renal (e.g., kidney) transplants. This study will determine whether a combination of anti-rejection drugs, including belatacept, can prevent the rejection of a first-time, non-human leukocyte antigen (HLA) identical renal transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.

Read the detailed description

Drugs that suppress the immune system have contributed to increased success of transplantation; however, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives. These drugs make patients more susceptible to infection and certain kinds of cancer. Belatacept is an experimental medication that specifically targets immune reactions against transplanted organs and has been shown to be effective in preventing kidney transplant rejection in previous clinical trials. Both thymoglobulin, an antibody, and sirolimus, an anti-rejection drug, prevent rejection by lowering the response of the immune system to the transplanted organ. This study will evaluate whether belatacept, along with thymoglobulin and sirolimus, is safe in kidney transplant patients. The study will also evaluate this regimen's potential to allow tapering and eventual discontinuation of all immunosuppressive drugs.

This study will last up to 4 years. At the time of transplant, participants will begin an immunosuppressive treatment regimen consisting of thymoglobulin, sirolimus, and belatacept. Participants will receive infusions of thymoglobulin on days 1 through 4, and a combination of oral sirolimus (daily) and belatacept infusions at day 5, then weeks 2, 4, 8, and monthly for at least 2 years. Dose reduction of belatacept will occur at 12 weeks post-transplant. At Year 2, eligible participants may choose to begin drug withdrawal or continue study therapy through the end of the study. Study visits will occur weekly for the first two months, then monthly. These visits will include belatacept treatment, general medical assessments, blood and urine collection, and other assessments to determine overall health of the recipient's immune system and kidney transplant and to better understand the way the immune system works in the acceptance or rejection of organ transplants.

  • IMPORTANT NOTICE: * The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.
Being tested
Belatacept, Sirolimus, Anti-thymocyte globulin, methylprednisolone
Keywords
renal transplantation, kidney transplantation, renal allograft recipient, anti-rejection drugs, immunosuppression protocol, immunosuppression withdrawal

What participants receive

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

  • BelataceptDrug

    Also called LEA29Y, Nulojix

    10 mg/kg given intravenously (IV) on transplant (day 1), day 5, and at weeks 2, 4, 8 and 12, then 5 mg/kg IV every 4 weeks

  • SirolimusDrug

    Also called Rapamycin, Rapamune

    4 mg/day (oral tablet) at transplant (day 1), then dose adjusted to maintain serum trough level of 8-12 ng/mL for at least 1 year

  • Anti-thymocyte globulinDrug

    Also called ATG, anti-thymocyte immunoglobulin, Thymoglobulin®

    1.5 mg/kg given IV daily on days 1 through 4. Subjects are premedicated with glucocorticoids, acetaminophen 650 mg by mouth, and diphenhydramine 25- 50 mg by mouth prior to each dose.

  • methylprednisoloneDrug

    Also called Medrol, glucocorticoid

    500 mg given IV at transplant (day 1), then given 250 mg IV on day 2 and given 0.5 mg/kg IV or prednisone 0.5 mg/kg given by mouth on days 3 and 4

Study groups in NCT00346151
Study groupRoleWhat they receive
BelataceptExperimentalImmunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus.
Receives: Drug: Belatacept; Drug: Sirolimus; Drug: Anti-thymocyte globulin; Drug: methylprednisolone

What is being measured

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

  1. Acute Rejection at 6-Months

    Cumulative incidence of acute rejection[1] at 6 months post-transplant based on local pathology biopsy reads

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

    Measured: 6 months post-transplant

Secondary outcomes (14)

  1. Participant Survival at 12 Months Post-Transplant

    Measured: 12 months post-transplant

  2. Acute Rejection at 12-Months

    Incidence of acute rejection[1] at 12 months post-transplant

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

    Measured: 12 months post-transplant

  3. Tolerance Induction

    Time from transplantation to initiation of sirolimus withdrawal.

    Measured: 48 months

  4. Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks

    GFR utilizing clearance of iothalamate.

    GFR is an index of level of kidney function. A higher value means better kidney function.

    Measured: 24 weeks post-transplant

  5. Graft Survival at 12 Months Post-transplant

    Measured: 12 months post-transplant

  6. Time From Transplant to Acute Rejection

    Time (days) from transplant to occurrence of acute rejection[1]

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

    Measured: Transplantation until rejection occurs (participants followed up to four years post-transplantation)

  7. Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection

    Proportion of participants who experienced acute rejection[1] requiring antilymphocyte therapy

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

    Measured: Participants followed from transplantation until completion of study (up to four years post-transplantation)

  8. Proportion of Participants With Post-transplant Infections

    Proportion of participants who experienced infections post-transplant. Participants were checked for any type of opportunistic infection at all study visits post-transplantation (up to 4 years post-transplantation)

    Measured: Participants followed from transplantation until completion of study (up to four years post-transplantation)

  9. Proportion of Participants With Wound Complications

    Measured: Start of study to end of study

  10. Proportion of Participants With Malignancies

    Measured: Participants followed from transplantation until completion of study (up to four years post-transplantation)

  11. Proportion of Participants With a Sirolimus Associated Adverse Event

    Measured: Participants followed from transplantation until completion of study (up to four years post-transplantation)

  12. Proportion of Participants With Chronic Allograft Nephropathy

    Measured: Participants followed from transplantation until completion of study (up to four years post-transplantation)

  13. Proportion of Participants With Delayed Graft Function

    Measured: Participants followed from transplantation until completion of study (up to four years post-transplantation)

  14. Proportion of Participants With Post-transplant Diabetes Mellitus

    Measured: Participants followed from transplantation until completion of study (up to four years post-transplantation)

Timeline

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

  1. First posted29 Jun 2006 (estimated)
  2. Study startDec 2006
  3. Primary completionFeb 2010
  4. Study completionFeb 2010

Why it stopped: Stopping rule-acute rejection threshold-was met based on local biopsy results

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00346151
Sponsor's protocol ID
DAIT ITN023ST
Acronym
BESTT
Status last verified
Mar 2017
First submitted
27 Jun 2006
Last updated
21 Apr 2017
Data monitoring committee
Yes
Individual data sharing
Yes: Data access is provided to the public in Participant level data and additional relevant materials are available to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.

Publications

  • Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G, Lang P, Grinyo J, Halloran PF, Solez K, Hagerty D, Levy E, Zhou W, Natarajan K, Charpentier B; Belatacept Study Group. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005 Aug 25;353(8):770-81. doi: 10.1056/NEJMoa050085.

    PubMed 16120857

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Belatacept, Sirolimus and Anti-thymocyte globulin in people with Renal Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.

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 8 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: stopped early, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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 7 Nov 2011). 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?

Acute Rejection at 6-Months (time frame: 6 months post-transplant). 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 NCT00346151, which also lists 1 linked publication.

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 21 Apr 2017.

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