Abatacept for Kidney Transplant Recipients

Recruiting at 21 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Calcineurin inhibitors, Mycophenolic acid, Steroids

Must not be taking: Immunomodulatory agents, Investigational drugs

Disqualifiers: HIV, Active Hepatitis B, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called abatacept (also known as Orencia) for individuals who have received a kidney transplant for the first time. The researchers aim to determine if switching from the usual medication, Tacrolimus, to abatacept can improve kidney function, mental abilities, and quality of life. Participants must be kidney transplant recipients who have not shown signs of rejection six months post-transplant. The trial will also assess whether a specific protein marker can predict future transplant success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that participants will transition from Tacrolimus to abatacept. This suggests you may need to change some medications, but it's best to discuss with the study team for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abatacept, a treatment tested for kidney transplant patients, has promising safety results. In various studies, abatacept has been used successfully in kidney transplant patients, with no failures of the transplanted kidney and positive patient outcomes. One study found that patients who switched to abatacept had a 100% survival rate over an average of 115 months.

Another study found that abatacept helped prevent a serious condition called acute graft-versus-host disease without major safety issues. However, in some trials, 54% of patients using abatacept reported infections, compared to 48% of those taking a placebo. While this might seem high, it is common for transplant patients on drugs that suppress the immune system. Overall, these findings suggest abatacept is generally well-tolerated, but like all treatments, it has some risks. Prospective trial participants should consult their doctor to determine if this treatment is suitable for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard of care for kidney transplant recipients, which typically involves medications like tacrolimus, mycophenolate mofetil, and prednisone, abatacept offers a unique approach. Abatacept works by selectively modulating the immune response, potentially reducing the risk of rejection with fewer side effects linked to long-term use of calcineurin inhibitors like tacrolimus. Researchers are excited about this treatment because it could improve renal function and neurocognitive outcomes, while also enhancing patients' quality of life. With its distinct mechanism of action, abatacept may represent a breakthrough in transplant medicine by offering a safer, more effective alternative to existing therapies.

What evidence suggests that this trial's treatments could be effective for kidney transplant recipients?

Research suggests that abatacept, which participants in this trial may receive, could benefit kidney transplant patients. Studies have shown that patients who switched from calcineurin inhibitors (CNI) to abatacept achieved successful transplant organ survival. One review reported 100% survival for both patients and their transplanted kidneys. Another study found that 79.6% of patients continued using abatacept, and 63.4% of them experienced structural remission, meaning their transplants functioned well without problems. These findings indicate that abatacept could be a safe and effective option for protecting transplanted kidneys and improving outcomes for recipients. Meanwhile, the control group in this trial will continue with standard care treatment, which includes tacrolimus, mycophenolate mofetil (MMF), and prednisone. ^{1 4 6 7 8}

Who Is on the Research Team?

Peter S Heeger, M.D.

Principal Investigator

Cedars Sinai Medical Center: Transplantation

Peter Nickerson, M.D.

Principal Investigator

University of Manitoba Max Rady College of Medicine - Transplantation

Are You a Good Fit for This Trial?

This trial is for adult kidney transplant recipients who are on a stable medication regimen, have good kidney function (eGFRCKD-EPI 30-90 ml/min/1.73m^2) at 6 months post-transplant, and no acute rejection or significant infections. They must agree to use effective contraception and be able to consent. Exclusions include severe lung disease, certain viral infections like HIV or active hepatitis B, recent other vaccine or drug trials participation.

Inclusion Criteria

I am of childbearing age and have a negative pregnancy test.

I am eligible for or have received a compatible kidney transplant recently.

Vaccines up to date as per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials

Exclusion Criteria

I am currently using drugs that affect my immune system.

I have not been exposed to the Epstein-Barr virus and have received a kidney transplant.

Inability or unwillingness of a participant to give written informed consent or comply with study protocol including a mandated 6-mo kidney transplant biopsy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

0-6 months

Multiple visits during initial hospitalization

Observational Study

Participants are followed observationally to evaluate HLA-DR/DQ molecular mismatch (mMM) as a risk-stratifying prognostic biomarker

24 months

Regular follow-up visits

Nested RCT Randomization

Eligible participants are randomized to abatacept or Standard of Care (SOC) and followed for safety and improvement in renal function, neurocognitive function, and life participation

18 months

Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Standard of Care

Trial Overview The study first observes 800 patients to see if their HLA-DR/DQ mismatch score can predict immune system risk after a transplant. Then it randomly assigns 300 eligible patients either to continue standard care or switch from Tacrolimus to Abatacept treatment, monitoring kidney function improvement and quality of life for 18 months.

How Is the Trial Designed?

Group I: Nested RCT - Treatment Group (Abatacept) Experimental Treatment 1 Intervention

Eligible subjects will be re-consented and randomized to the investigational (abatacept/Mycophenolate mofetil (MMF)/Pred) Arm. Starting with abatacept at a fixed dose (125 mg s.c. weekly) and eliminate Calcineurin Inhibitor (CNI) over \~3 months using serial Tacrolimus (TAC) C0 level targets to taper the dose. 2200 subjects will be followed for 18 months post-randomization, monitoring for safety and improvement in renal function, neurocognitive function, and a life participation patient reported outcome measure (PROM). Subjects who develop Biopsy Proven Acute Rejection (BPAR) will have concurrent serum/urine/tissue samples collected and stored.

Group II: Nested RCT - Control Group (SOC) Active Control 1 Intervention

Eligible subjects will be re-consented and randomized to the control group (tacrolimus/Mycophenolate mofetil (MMF)/Pred) . 100 subjects will be and followed for 18 months post-randomization, monitoring for safety and improvement in renal function, neurocognitive function, and a life participation patient reported outcome measure (PROM). Subjects who develop Biopsy Proven Acute Rejection (BPAR) will have concurrent serum/urine/tissue samples collected and stored.

Group III: Observational Study - Full Cohort Active Control 1 Intervention

800 adults first kidney transplant recipients will be followed observationally to evaluate HLA-DR/DQ molecular mismatch (mMM) as a risk-stratifying prognostic biomarker. Donor-recipient HLA-DR/DQ mMM score will be determined at enrollment and recipients will be followed over 24-months post-kidney transplant for primary alloimmune events (i.e., TCMR, DSA, and ABMR). Standard of care (SOC) therapy will be used to satisfy the FDA requirement to prospectively evaluate the HLA-DR/DQ mMM score as a prognostic biomarker for post-kidney transplant outcomes.

Abatacept is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in United States as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a 2-year observational study of 100 patients with moderate to severe rheumatoid arthritis in Austria, abatacept showed a high overall retention rate of 60.5%, with better retention in biologic-naïve patients (65.1%) compared to those with prior biologic failures (58.0%).

The study found that good/moderate EULAR response rates were notably high, reaching 100% in biologic-failure patients, indicating that abatacept can be particularly effective for those who have not responded to previous biologic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept retention and clinical outcomes in Austrian patients with rheumatoid arthritis: real-world data from the 2-year ACTION study. Peichl, P., Alten, R., Galeazzi, M., et al.[2020]

In a study of 137 rheumatoid arthritis patients treated with abatacept for 24 weeks, significant improvements in disease activity were observed, with SDAI scores decreasing from 24.6 to 12.9 and DAS28-ESR scores from 5.2 to 3.9, indicating effective management of the disease.

The retention rate of abatacept was high at 79.6%, and structural remission was achieved in 63.4% of patients, suggesting that abatacept is a safe and effective first-line biologic treatment for rheumatoid arthritis, particularly in biologic-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of abatacept in routine care of patients with rheumatoid arthritis: Orencia(®) as Biological Intensive Treatment for RA (ORBIT) study. Tanaka, Y., Kubo, S., Yamanaka, H., et al.[2016]

In the ACTION study, which included 677 patients with rheumatoid arthritis in Germany, the retention rate of abatacept at 2 years was 39.9%, with biologic-naïve patients showing a significantly lower retention rate compared to those from other countries (42.1% vs. 58.7%).

Despite similar retention rates between biologic-naïve and biologic-failure patients in Germany, the EULAR response rates for biologic-naïve patients were lower in Germany (85.5%) compared to other countries (92.1%), suggesting potential differences in treatment effectiveness or patient management across regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept retention and clinical outcomes in rheumatoid arthritis: real-world data from the German cohort of the ACTION study and a comparison with other participating countries. Alten, R., Feist, E., Lorenz, HM., et al.[2020]

In a study of 9 kidney transplant recipients who could not tolerate calcineurin inhibitors, switching to abatacept as a rescue immunosuppressive therapy resulted in 100% patient and graft survival over a median follow-up of 115 months.

Patients maintained stable renal function while on abatacept for a median of 82 months, with only one episode of cellular rejection, suggesting that abatacept could be a viable alternative for patients intolerant to traditional immunosuppressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation. Badell, IR., Karadkhele, GM., Vasanth, P., et al.[2023]

Abatacept significantly improves health outcomes in patients with rheumatoid arthritis, showing higher likelihoods of achieving American College of Rheumatology (ACR) response rates compared to placebo and other treatments, based on a meta-analysis of 13 randomized control trials involving 5978 patients.

Patients treated with abatacept experienced fewer adverse events compared to those receiving other biologic disease-modifying anti-rheumatic drugs, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. Mohamed Ahamada, M., Wu, X.[2023]

In a study of 2350 patients with moderate-to-severe rheumatoid arthritis, abatacept showed a 2-year retention rate of 47.9%, with higher rates in biologic-naive patients (54.5%) compared to those with prior biologic failures (45.2%).

The main reasons for discontinuation were lack of efficacy (61.4% in biologic-naive vs 67.7% in biologic-failure patients) and safety concerns, while seropositivity for rheumatoid factor and anti-CCP was associated with better retention rates, suggesting these factors could help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study. Alten, R., Mariette, X., Lorenz, HM., et al.[2021]

The study found that 60% of rheumatoid arthritis patients were aware of the patient alert cards (PACs) for abatacept, and those who received the PACs had significantly better knowledge about the risk of infections compared to those who did not (64% vs 46%).

Among healthcare professionals, 90% were aware of the PACs, and those who accessed the cards had a higher understanding of infection risks (91% vs 73%), indicating that PACs effectively enhance safety knowledge for both patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linking process indicators and clinical/safety outcomes to assess the effectiveness of abatacept (ORENCIA) patient alert cards in patients with rheumatoid arthritis. Artime, E., Kahlon, R., Méndez, I., et al.[2021]

Abatacept (Orencia) significantly improves symptoms of active rheumatoid arthritis and slows joint damage progression in patients who have previously been treated with other therapies, based on results from two phase III trials involving multiple centers over 6 to 12 months.

The treatment is generally well tolerated, with similar rates of serious adverse events between abatacept and placebo, although it may be less well tolerated when combined with other biologic DMARDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept. Hervey, PS., Keam, SJ.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9411423/

Abatacept Rescue Therapy in Kidney Transplant Recipients This letter reports on our experience with CNI conversion to self-administered subcutaneous abatacept in five patients who benefited from RT for 1.5–84 months.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522091997

Abatacept as rescue immunosuppression after calcineurin ... Retrospective review revealed successful allograft salvage and 100% patient and graft survival (median 115 months) after conversion to abatacept. Patients ...

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-abatacept-prophylaxis-acute-graft-versus-host-disease

FDA approves abatacept for prophylaxis of acute graft The OS rate at Day 180 after HSCT was 98% (95% CI: 78%, 100%) for patients who received abatacept in combination with CNI and MTX compared to 75 ...

4. withpower.com withpower.com/trial/phase-2-kidney-transplantation-6-2023-de5de

Abatacept for Kidney Transplant Recipients The retention rate of abatacept was high at 79.6%, and structural remission was achieved in 63.4% of patients, suggesting that abatacept is a safe and effective ...

5. amjtransplant.org amjtransplant.org/article/S1600-6135(25)00971-2/fulltext

Late Abatacept Conversion in Kidney Transplant ... Purpose: Immunosuppression with belatacept in kidney transplantation results in superior outcomes as compared to calcineurin inhibitors.

6. orenciahcp.com orenciahcp.com/safety-data.html

Safety Data | ORENCIA® (abatacept) In placebo-controlled trials, infections were reported in 54% of ORENCIA-treated patients and 48% of placebo-treated patients. The most commonly reported ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38265815/

Long-Term Outcomes after Conversion to a Belatacept ... This real-world evidence study shows that conversion to belatacept post-transplant was associated with lower risk of graft failure and acceptable safety ...

8. ashpublications.org ashpublications.org/blood/article/142/8/700/496372/Higher-abatacept-exposure-after-transplant

Higher abatacept exposure after transplant decreases acute ... In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease ( ...