Failing Renal AllograftPhase 3IM103-133NCT01921218
Belatacept Therapy for the Failing Renal Allograft
A Phase 3 study testing Belatacept, Calcineurin inhibitor therapy and Mycophenolate mofetil in people with Failing Renal Allograft, run by Andrew B Adams at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and effectiveness of belatacept (Nulojix®) in preventing antibody formation in patients with chronic failing kidney transplants. This study is a randomized study of first-time kidney transplant patients who have worsening kidney function and biopsy proven grade 2 or 3… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Failing Renal Allograft
- What is being tested?
- Belatacept, Calcineurin inhibitor therapy and Mycophenolate mofetil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to 12 Dec 2019
- Phase
- Phase 3
- 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
- Signed written informed consent
- Kidney transplant recipient (human leukocyte antigen (HLA) non-identical donor) who now has impaired renal allograft function with:
- Estimated glomerular filtration rate (GFR) < 35 with a decline in GFR of > 10% in the 12 months prior to enrollment and must have biopsy proven grade II or III interstitial fibrosis/tubular atrophy (IF/TA) OR
- Estimated GFR persistently < 20 ml/min over the 6 month period prior to enrollment absent other causes for graft dysfunction, and deemed to have a failing allograft by the patient's transplant nephrologist
- On a maintenance immunosuppressive regimen that includes calcineurin inhibitor (CNI)(tacrolimus or cyclosporine) or sirolimus and at least
- MMF of a dose of at least 1 gm/day or comparable dose of azathioprine OR
- Prednisone at a dose of at least 5 mg/day
- Men and women, ages 18 to 70, inclusive
Who cannot join
- Women of childbearing potential (WOCBP) who are 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 drug.
- Women who are pregnant or breastfeeding.
- Women with a positive pregnancy test.
- Sexually active fertile men not using effective birth control if their partners are WOCBP.
- Subjects who are Epstein-Barr Virus (EBV) seronegative.
- Subjects with any prior solid organ (e.g., heart, liver, pancreas) or cell (e.g., islet, bone marrow) transplant other than a renal allograft. Exception may be made for recipient of a simultaneous kidney-pancreas transplant who had previously experienced graft loss of the pancreas allograft due to thrombosis or rejection.
Show all 20Show fewer
- Subjects with presence of donor specific antibody at the time of enrollment
- Subjects who have a recent history (within 1 yr) of biopsy proven acute rejection > Banff grade Ia
- Subjects who have a living donor identified for re-transplant within 3 months
- Subjects with a history of post-transplant lymphoproliferative disease (PTLD)
- Subjects at risk for tuberculosis (TB)
- Subjects with a history of cancer within the past 3 years, other than non-melanoma skin cancer(s)
- Subjects with a positive BK virus serum polymerase chain reaction (PCR) > 20,000 copies at the time of enrollment OR history of biopsy-proven BK nephropathy within the year prior to enrollment.
- Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations
- Subjects who have difficult intravenous access or other reasons that would likely preclude the ability to receive long-term intravenous infusions
- Hypersensitivity to any medications that will be used in the protocol
- Subjects who have used any investigational drug within the 30 days prior to anticipated enrollment
- Subjects currently receiving belatacept as part of their maintenance immunosuppressive regimen
- Prisoners, or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to test the safety and effectiveness of belatacept (Nulojix®) in preventing antibody formation in patients with chronic failing kidney transplants. This study is a randomized study of first-time kidney transplant patients who have worsening kidney function and biopsy proven grade 2 or 3 interstitial fibrosis/tubular atrophy (IF/TA). Patients must be eligible to get a second transplant. They must have completed or be actively undergoing evaluation for re-listing for a second transplant. Patients will be randomized to either convert to belatacept or continue on calcineurin inhibitor-based therapy.
Read the detailed description
The purpose of this study is to test the safety and effectiveness of the medicine belatacept (Nulojix®) in preventing antibodies from forming in people with a failing kidney transplant. Kidney transplant patients take immunosuppression medicines to prevent kidney rejection. When a kidney transplant begins to fail, the immunosuppression medicines are slowly weaned. Once dialysis is started, the immunosuppressant medicines are usually stopped. After immunosuppression is stopped, some people form antibodies. Antibodies are proteins that the immune system makes to protect against harmful foreign substances like bacteria, viruses, or foreign tissues, like a transplant. High levels of antibodies can make it harder to find a kidney donor for that person.
Participants will be randomized into one of the two treatment groups. One group will continue taking their current immunosuppression medicines. The people in the treatment group will be switched to belatacept (Nulojix®). Belatacept (Nulojix®) is an immunosuppression medicine that is approved by the U.S. Food and Drug Administration (the FDA) to prevent rejection in kidney transplant. Participants will stop taking calcineurin inhibitors (either cyclosporine or tacrolimus) or sirolimus but will keep taking other immunosuppression medicines like Cellcept (MMF) or azathioprine (Imuran) and prednisone. These medicines will be slowly weaned and will be stopped if the participant has to start dialysis. Participants will continue taking belatacept (Nulojix®), even while on dialysis.
The study team will test both groups to see how many people in each group develop antibodies.
- Conditions
- Failing Renal Allograft
- Being tested
- Belatacept, Calcineurin inhibitor therapy, Mycophenolate mofetil, prednisone
- Keywords
- Kidney transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelataceptDrug
Also called Nulojix
Belatacept, dosing 10mg/kg- day 0, 2 weeks, 1 month, 2 months, 3 months; subsequent doses 5mg/kg monthly through duration of trial or until retransplantation, whichever is first.
Calcineurin inhibitor therapyDrug
Also called tacrolimus, cyclosporine
Upon enrollment, wean calcineurin inhibitor (CNI) to target tacrolimus trough of 3-5 nanogram/milliliter (ng/ml)or equivalent cyclosporine trough. Upon initiation of hemodialysis, discontinue CNI therapy over 5 days.
Also called Cellcept
Continue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later
prednisoneDrug
Also called Deltasone
Begin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Belatacept (Nulojix) IV Receives: Drug: Belatacept; Drug: Mycophenolate mofetil; Drug: prednisone |
| Control | Active comparator | Calcineurin inhibitor based therapy (cyclosporine or tacrolimus) Receives: Drug: Calcineurin inhibitor therapy; Drug: Mycophenolate mofetil; Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Donor-specific Antibody Formation
The number of participants in each group with donor-specific antibody formation at 36 months following randomization.
Measured: Month 36
Secondary outcomes (4)
Glomerular Filtration Rate (GFR)
The glomerular filtration rate (GFR) assesses kidney function. GFR uses values for serum creatinine (SCr) measured in mg/dL, age in years, blood urea nitrogen (BUN) measures in mg/dL, and serum albumin (Alb) measured in g/dL. GFR is calculated as 170 x (SCr/0.95)^(-0.999) x (Age)^(-0.176) x (0.762 if the patient is female) x (1.180 if the patient is black) x (BUN)^(-0.170) x (Alb)^(0.318). A value of 90 or above is considered normal while values between 15 and 29 indicate severely decreased kidney function and values below 15 indicate kidney failure. The GFR in participants who do not require dialysis will be followed for two years.
Measured: Baseline up to Month 24
Time to Initiation of Dialysis
Time to dialysis is measured as the time of randomization to initiation of dialysis. Participants already requiring dialysis at the time of enrollment were excluded from this endpoint analysis.
Measured: Up to Year 2
Number of Participants With Anti-human Leukocyte Antigen (HLA) Alloantibodies
The presence of anti-HLA Class I and Class II alloantibodies is categorized as being negative (absent for both classes of alloantibodies), positive for Class I, positive for Class II, and positive for both Class I and Class II alloantibodies.
Measured: Baseline up to Month 36
Number of Infectious Complications
The number of infections complications occurring among study participants is presented here.
Measured: Baseline up to Month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2013 (estimated)
- Study startAug 2013
- Primary completion12 Dec 2019
- Study completion12 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Failing Renal AllograftStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrew B Adams
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Andrew B Adams, Emory University
- Investigators
- Andrew B Adams, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01921218
- Sponsor's protocol ID
- IRB00060470
- Other IDs
- IM103-133
- Acronym
- IM103-133
- Status last verified
- Jan 2021
- First submitted
- 9 Aug 2013
- Last updated
- 26 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Belatacept Therapy for the Failing Renal Allograft
- ClinicalTrials.gov ID
- NCT01921218
- Acronym / sponsor ID
- IM103-133 / IRB00060470
- Conditions
- Failing Renal Allograft
- Keywords
- Kidney transplant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Andrew B AdamsUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Aug 2013
- Primary completion
- 12 Dec 2019 (actual)
- Study completion
- 12 Dec 2019 (actual)
- First posted
- 13 Aug 2013 (estimated)
- Results
- Posted 26 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety and effectiveness of belatacept (Nulojix®) in preventing antibody formation in patients with chronic failing kidney transplants. This study is a randomized study of first-time kidney transplant patients who have worsening kidney function and biopsy proven grade 2 or 3 interstitial fibrosis/tubular atrophy (IF/TA). Patients must be eligible to get a second transplant. They must have completed or be actively undergoing evaluation for re-listing for a second transplant. Patients will be randomized to either convert to belatacept or continue on calcineurin inhibitor-based therapy.
Detailed description
The purpose of this study is to test the safety and effectiveness of the medicine belatacept (Nulojix®) in preventing antibodies from forming in people with a failing kidney transplant. Kidney transplant patients take immunosuppression medicines to prevent kidney rejection. When a kidney transplant begins to fail, the immunosuppression medicines are slowly weaned. Once dialysis is started, the immunosuppressant medicines are usually stopped. After immunosuppression is stopped, some people form antibodies. Antibodies are proteins that the immune system makes to protect against harmful foreign substances like bacteria, viruses, or foreign tissues, like a transplant. High levels of antibodies can make it harder to find a kidney donor for that person.
Participants will be randomized into one of the two treatment groups. One group will continue taking their current immunosuppression medicines. The people in the treatment group will be switched to belatacept (Nulojix®). Belatacept (Nulojix®) is an immunosuppression medicine that is approved by the U.S. Food and Drug Administration (the FDA) to prevent rejection in kidney transplant. Participants will stop taking calcineurin inhibitors (either cyclosporine or tacrolimus) or sirolimus but will keep taking other immunosuppression medicines like Cellcept (MMF) or azathioprine (Imuran) and prednisone. These medicines will be slowly weaned and will be stopped if the participant has to start dialysis. Participants will continue taking belatacept (Nulojix®), even while on dialysis.
The study team will test both groups to see how many people in each group develop antibodies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Belatacept, Drug: Mycophenolate mofetil, Drug: prednisoneBelatacept (Nulojix) IV |
| Control | Active comparator | Drug: Calcineurin inhibitor therapy, Drug: Mycophenolate mofetil, Drug: prednisoneCalcineurin inhibitor based therapy (cyclosporine or tacrolimus) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed written informed consent
- Kidney transplant recipient (human leukocyte antigen (HLA) non-identical donor) who now has impaired renal allograft function with:
- Estimated glomerular filtration rate (GFR) < 35 with a decline in GFR of > 10% in the 12 months prior to enrollment and must have biopsy proven grade II or III interstitial fibrosis/tubular atrophy (IF/TA) OR
- Estimated GFR persistently < 20 ml/min over the 6 month period prior to enrollment absent other causes for graft dysfunction, and deemed to have a failing allograft by the patient's transplant nephrologist
- On a maintenance immunosuppressive regimen that includes calcineurin inhibitor (CNI)(tacrolimus or cyclosporine) or sirolimus and at least
Key exclusion criteria (20 listed)
- Women of childbearing potential (WOCBP) who are 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 drug.
- Women who are pregnant or breastfeeding.
- Women with a positive pregnancy test.
- Sexually active fertile men not using effective birth control if their partners are WOCBP.
- Subjects who are Epstein-Barr Virus (EBV) seronegative.
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 |
|---|---|---|
| BelataceptAlso: NulojixBelatacept, dosing 10mg/kg- day 0, 2 weeks, 1 month, 2 months, 3 months; subsequent doses 5mg/kg monthly through duration of trial or until retransplantation, whichever is first. | Drug | Treatment |
| Calcineurin inhibitor therapyAlso: tacrolimus, cyclosporineUpon enrollment, wean calcineurin inhibitor (CNI) to target tacrolimus trough of 3-5 nanogram/milliliter (ng/ml)or equivalent cyclosporine trough. Upon initiation of hemodialysis, discontinue CNI therapy over 5 days. | Drug | Control |
| Mycophenolate mofetilAlso: CellceptContinue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later | Drug | Control, Treatment |
| prednisoneAlso: DeltasoneBegin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis | Drug | Control, Treatment |
Primary outcome
Number of Participants With Donor-specific Antibody Formation
Time frame: Month 36
The number of participants in each group with donor-specific antibody formation at 36 months following randomization.
4 secondary outcomes
Glomerular Filtration Rate (GFR)
Time frame: Baseline up to Month 24
Time to Initiation of Dialysis
Time frame: Up to Year 2
Number of Participants With Anti-human Leukocyte Antigen (HLA) Alloantibodies
Time frame: Baseline up to Month 36
Number of Infectious Complications
Time frame: Baseline up to Month 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Andrew B Adams, MD, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Belatacept, Calcineurin inhibitor therapy and Mycophenolate mofetil in people with Failing Renal Allograft, run by Andrew B Adams at 1 site 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 8 inclusion and 20 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 26 Jan 2021. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 26 Jan 2021). 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 Donor-specific Antibody Formation (time frame: Month 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jan 2021.