Kidney TransplantationPhase 2NCT00001857
Study Comparing the Safety of BG9588 (Anti-CD40L Antibody) Against Standard Treatment in Kidney Transplantation
A Phase 2 study testing BG9588 in people with Kidney Transplantation, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
The most common problem following a kidney transplant is the development of acute or chronic rejection. Rejection is the immunologic reaction in which the body refuses to accept the transplanted organ. The body's immune system will make destructive antibodies that will attempt to attack the transplanted organ. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- BG9588
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- May 1999to Apr 2000
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Must be a candidate for a renal transplant from a living related, living non-related, or cadaveric donor.
Must be willing and able to give written informed consent.
Aged between 18 and 65 years, inclusive. Subjects over the age of 65 may be considered on an individual basis based on medical suitability.
Female subjects must be post-menopausal or surgically sterile, or using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable).
WBC count must be greater than or equal to 3000/mm(2).
No history of malignancy (except non-metastatic cutaneous squamous or basal cell carcinomas that have been completely excised without evidence of recurrence for at least 1 year).
No active systemic bacterial, fungal or viral infections (including active zoster or herpetic lesions).
No serological evidence of HIV, HCV, or HbsAg.
No active peptic ulcer disease.
No condition or circumstance that could potentially interfere with the evaluation of BG9588.
No contraindication to monoclonal antibody therapies.
No history of Major Thromboembolic event (e.g. stroke, pulmonary embolus).
For the first 5 patients, no patient with a PRA greater than 20%.
No previous participation in the study.
No use of any investigational agent or device within 4 weeks prior to first dose of study drug.
No Cold Ischemia Time of donor kidney greater than 36 hours.
No uncontrolled non-heart-beating donor status.
No positive T-cell Crossmatch.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Bethesda, Maryland, 20892
About this study
Official title: A Multicenter, Open-Label, Study to Determine the Safety of BG9588 (Anti-CD40L Antibody) Therapy Compared to Standard Treatment in Renal Allograft Transplantation
The most common problem following a kidney transplant is the development of acute or chronic rejection. Rejection is the immunologic reaction in which the body refuses to accept the transplanted organ. The body's immune system will make destructive antibodies that will attempt to attack the transplanted organ.
In order to prevent organ rejection, all patients receiving an allograft (a graft transplanted between genetically non-identical individuals of the same species) must take anti-rejection therapy. These medications function by lowering the body's natural immune system. Often these medications are associated with significant side effects ranging from infections to cancer.
Read more
This study is designed to test whether the drug presently known as BG9588 (Antova TM) can reduce the incidence of organ rejection following kidney transplants in humans. More specifically, the study will attempt to assess the safety of BG9588 when given alone or when given in combination with other anti-rejection therapies. Safety will be measured by the amount of acute or chronic rejections, and immunological graft losses.
Subjects for the study will be made up of non-human primates (monkeys) and humans. Up to 5 subjects in each of the groups receiving kidney transplants will be placed on a 12 month course of BG9588 with or without additional anti-rejection drugs. BG9588 will be given intravenously (injected through a vein) prior to the transplant and then in a decreased dose with a decreased frequency over the year. Following the 12 months of therapy subjects may be eligible for additional monthly therapy.
The long-term follow up will occur through 30 months after the last dose of BG9588. Subjects will undergo periodic tests and evaluations throughout the course of the study. These tests will assess the body's immune system and detect the presence of rejection.
Read the detailed description
This protocol is an open label, non-randomized study designed to test whether treatment with BG9588, a humanized monoclonal antibody specific for CD154, can induce a state of allograft tolerance following renal allotransplantation in humans. This study is designed to primarily assess the safety and efficacy of BG9588 when given alone or in combination with steroids and mycophenolate to prevent renal allograft rejection without the use of calcineurin inhibitors or other chronic anti-rejection therapies. Efficacy parameters will include the incidence of acute and chronic rejection episodes, and immunological graft loss. Additional evaluation will be performed to specifically assess the development of donor-specific immune hyporesponsiveness resulting from the use of BG9588.
This study is based on extensive use of BG9588 in non-human primates and pilot evaluation in humans. Up to five patients in each group receiving primary renal allografts will be treated with a 12-month course of BG9588 with or without steroids and mycophenolate to prevent allograft rejection. The recruitment will be performed first in the group with steroids and mycophenolate. Subjects will receive BG9588 at a dose of 70 mg/kg (based on ideal body weight at baseline) via a continuous 60 minute IV infusion within 24 hours pre-operatively followed by a 30 mg/kg dose via a continuous 30 minute IV infusion on the following days: within 24 hours post-transplantation, and on days 3, 10, 18, 28, then monthly through 12 months post-transplantation. The enrollment will be staggered such that early efficacy will be demonstrated in 5 patients prior to completing enrollment. Following 12 months of therapy, patients may be extended to receive additional monthly therapy.
Long-term follow up will occur through 30 months after the last dose of BG9588. Mechanistic evaluations testing for allograft tolerance will be performed throughout the study including evaluations for allospecific T cell deletion, allospecific T cell anergy, and alloantibody production. The donor population for this study will include both living donors and cadaveric donors. This is being done to address the theoretical concern that ischemic reperfusion injury may negatively affect the efficacy of BG9588.
- Conditions
- Kidney Transplantation
- Being tested
- BG9588
- Keywords
- Costimulation, Immunosuppression, Tolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BG9588Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startMay 1999
- Study completionApr 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001857
- Sponsor's protocol ID
- 990109
- Other IDs
- 99-DK-0109
- Status last verified
- May 1999
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Eggers PW. Effect of transplantation on the Medicare end-stage renal disease program. N Engl J Med. 1988 Jan 28;318(4):223-9. doi: 10.1056/NEJM198801283180406.
PubMed 3275896Morris PJ. Renal transplantation: a quarter century of achievement. Semin Nephrol. 1997 May;17(3):188-95.
PubMed 9165648Gaber AO, First MR, Tesi RJ, Gaston RS, Mendez R, Mulloy LL, Light JA, Gaber LW, Squiers E, Taylor RJ, Neylan JF, Steiner RW, Knechtle S, Norman DJ, Shihab F, Basadonna G, Brennan DC, Hodge EE, Kahan BD, Kahan L, Steinberg S, Woodle ES, Chan L, Ham JM, Schroeder TJ, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation. 1998 Jul 15;66(1):29-37. doi: 10.1097/00007890-199807150-00005.
PubMed 9679818
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Study to Determine the Safety of BG9588 (Anti-CD40L Antibody) Therapy Compared to Standard Treatment in Renal Allograft Transplantation
- ClinicalTrials.gov ID
- NCT00001857
- Acronym / sponsor ID
- 990109
- Conditions
- Kidney Transplantation
- Keywords
- Costimulation, Immunosuppression, Tolerance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- May 1999
- Study completion
- Apr 2000
- First posted
- 10 Dec 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The most common problem following a kidney transplant is the development of acute or chronic rejection. Rejection is the immunologic reaction in which the body refuses to accept the transplanted organ. The body's immune system will make destructive antibodies that will attempt to attack the transplanted organ.
In order to prevent organ rejection, all patients receiving an allograft (a graft transplanted between genetically non-identical individuals of the same species) must take anti-rejection therapy. These medications function by lowering the body's natural immune system. Often these medications are associated with significant side effects ranging from infections to cancer.
This study is designed to test whether the drug presently known as BG9588 (Antova TM) can reduce the incidence of organ rejection following kidney transplants in humans. More specifically, the study will attempt to assess the safety of BG9588 when given alone or when given in combination with other anti-rejection therapies. Safety will be measured by the amount of acute or chronic rejections, and immunological graft losses.
Subjects for the study will be made up of non-human primates (monkeys) and humans. Up to 5 subjects in each of the groups receiving kidney transplants will be placed on a 12 month course of BG9588 with or without additional anti-rejection drugs. BG9588 will be given intravenously (injected through a vein) prior to the transplant and then in a decreased dose with a decreased frequency over the year. Following the 12 months of therapy subjects may be eligible for additional monthly therapy.
The long-term follow up will occur through 30 months after the last dose of BG9588. Subjects will undergo periodic tests and evaluations throughout the course of the study. These tests will assess the body's immune system and detect the presence of rejection.
Detailed description
This protocol is an open label, non-randomized study designed to test whether treatment with BG9588, a humanized monoclonal antibody specific for CD154, can induce a state of allograft tolerance following renal allotransplantation in humans. This study is designed to primarily assess the safety and efficacy of BG9588 when given alone or in combination with steroids and mycophenolate to prevent renal allograft rejection without the use of calcineurin inhibitors or other chronic anti-rejection therapies. Efficacy parameters will include the incidence of acute and chronic rejection episodes, and immunological graft loss. Additional evaluation will be performed to specifically assess the development of donor-specific immune hyporesponsiveness resulting from the use of BG9588.
This study is based on extensive use of BG9588 in non-human primates and pilot evaluation in humans. Up to five patients in each group receiving primary renal allografts will be treated with a 12-month course of BG9588 with or without steroids and mycophenolate to prevent allograft rejection. The recruitment will be performed first in the group with steroids and mycophenolate. Subjects will receive BG9588 at a dose of 70 mg/kg (based on ideal body weight at baseline) via a continuous 60 minute IV infusion within 24 hours pre-operatively followed by a 30 mg/kg dose via a continuous 30 minute IV infusion on the following days: within 24 hours post-transplantation, and on days 3, 10, 18, 28, then monthly through 12 months post-transplantation. The enrollment will be staggered such that early efficacy will be demonstrated in 5 patients prior to completing enrollment. Following 12 months of therapy, patients may be extended to receive additional monthly therapy.
Long-term follow up will occur through 30 months after the last dose of BG9588. Mechanistic evaluations testing for allograft tolerance will be performed throughout the study including evaluations for allospecific T cell deletion, allospecific T cell anergy, and alloantibody production. The donor population for this study will include both living donors and cadaveric donors. This is being done to address the theoretical concern that ischemic reperfusion injury may negatively affect the efficacy of BG9588.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BG9588 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 3275896Eggers PW. Effect of transplantation on the Medicare end-stage renal disease program. N Engl J Med. 1988 Jan 28;318(4):223-9. doi: 10.1056/NEJM198801283180406.
- Background: PubMed 9165648Morris PJ. Renal transplantation: a quarter century of achievement. Semin Nephrol. 1997 May;17(3):188-95.
- Background: PubMed 9679818Gaber AO, First MR, Tesi RJ, Gaston RS, Mendez R, Mulloy LL, Light JA, Gaber LW, Squiers E, Taylor RJ, Neylan JF, Steiner RW, Knechtle S, Norman DJ, Shihab F, Basadonna G, Brennan DC, Hodge EE, Kahan BD, Kahan L, Steinberg S, Woodle ES, Chan L, Ham JM, Schroeder TJ, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation. 1998 Jul 15;66(1):29-37. doi: 10.1097/00007890-199807150-00005.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BG9588 in people with Kidney Transplantation, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001857, which also lists 3 linked publications.
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 4 Mar 2008.