Abatacept for Kidney Transplant Recipients

Recruiting in Palo Alto (17 mi)

+20 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

800 adult first time kidney transplant recipients will be enrolled in the Observational Study and followed to evaluate their Human Leukocyte Antigen (HLA)-DR/DQ molecular mismatch (mMM) score as a risk-stratifying prognostic biomarker. Six months after transplant the study will identify those who meet the eligibility criteria for the Nested Randomized Control Trial (RCT). 300 eligible subjects will be randomized 2:1 to abatacept or Standard of care (SOC) in the randomization and followed for 18 months monitoring for safety and improvement in renal function, neurocognitive function, and a life participation patient reported outcome measure (PROM). The primary objective of the Observational Study is to test the validity of the HLA-DR/DQ mMM score as a prognostic biomarker for stratification of post-transplant alloimmune risk. Whereas the objective of the Nested RCT is to test whether a superior outcome in kidney function (primary endpoint), as well as secondary endpoints (neurocognitive function, and life participation PROM), will be achieved in patients who are transitioned from Tacrolimus (TAC) to abatacept, while maintaining efficacy (freedom from biopsy proven acute rejection).

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.

What data supports the effectiveness of the drug abatacept for kidney transplant recipients?

A study involving kidney transplant recipients who could not tolerate standard immunosuppressive drugs showed that switching to abatacept helped maintain kidney function and patient survival over a long period. This suggests abatacept could be a promising option for these patients.

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Is abatacept generally safe for humans?

Abatacept (Orencia) has been studied for rheumatoid arthritis and is generally considered safe, but it may increase the risk of infections and allergic reactions. Patient alert cards are used to inform patients and healthcare professionals about these risks.

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How does the drug abatacept differ from other treatments for kidney transplant recipients?

Abatacept is unique because it is a selective costimulation modulator that inhibits the full activation of T cells, which are part of the immune system. This mechanism is different from other treatments that may not specifically target T cell activation, making it potentially beneficial for preventing immune-related complications in kidney transplant recipients.

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Eligibility Criteria

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

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Methodist Hospital: Transplantation Houston, TX

Mayo Clinic Rochester: Transplantation Rochester, MN

Cleveland Clinic Florida: Transplantation Weston, FL

Toronto General Hospital: Transplantation Toronto, Canada

More Trial Locations

Who Is Running the Clinical Trial?

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

References

1. Italy pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. [2023] Abatacept (Orencia) is a drug used to treat patients with rheumatoid arthritis. The agent improves patients' pain and joint inflammation through modulation of a co-stimulatory signal necessary for T cell activation. We aimed to analyse the efficacy and safety of abatacept in the management of rheumatoid arthritis using the Cochrane systematic review.

2. England 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. [2021] Patient alert cards (PACs) for abatacept (ORENCIA) inform patients and healthcare professionals (HCPs) about the risk of infections and allergic reactions. The study evaluates the effectiveness of the PACs in rheumatoid arthritis patients and HCPs, using process indicators (awareness, receipt, utility, knowledge, behaviour) and outcomes.

3. United States pubmed.ncbi.nlm.nih.gov

Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation. [2023] A majority of kidney transplant recipients receive calcineurin inhibitor-based immunosuppression. However, some do not tolerate calcineurin inhibitors and require other immunosuppressive strategies. Until recently, alternative approaches have been associated with inferior outcomes, but recent methods have effectively utilized belatacept in calcineurin inhibitor-intolerant patients. Though promising, belatacept uptake has been limited by higher acute rejection rates, unavailability due to production shortages, and logistical challenges as a result of intravenous infusion requirements. Interestingly, its predecessor abatacept is clinically available in subcutaneous formulation to treat autoimmune disorders but has not been used in clinical transplantation. Here we report on a series of 9 calcineurin inhibitor-intolerant transplant recipients converted to abatacept early after transplant as rescue immunosuppression during periods of belatacept unavailability. Retrospective review revealed successful allograft salvage and 100% patient and graft survival (median 115 months) after conversion to abatacept. Patients received abatacept for a median duration of 82 months with stable, long-term renal allograft function, a single cellular rejection episode, and no clinically apparent protective immunity concerns. Hence our findings suggest that future clinical studies utilizing abatacept either de novo or as conversion therapy in transplant recipients should be considered.

4. Austria 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. [2020] AbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was a 2-year international observational study of patients with moderate to severe rheumatoid arthritis.

5. New Zealand pubmed.ncbi.nlm.nih.gov

Abatacept. [2018] Abatacept (Orencia) is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the inflammatory cascade. The clinical efficacy of abatacept in patients with active rheumatoid arthritis, despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind, placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In these trials, patients received intravenous abatacept (fixed-dose regimen based on bodyweight) or placebo in addition to background disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo, abatacept significantly improved signs and symptoms of disease assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific improvement in physical function as measured by the Health Assessment Questionnaire Disability Index at 6 months and significantly slowed structural damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70 response rates were maintained at the final assessment in the 12-month trial. Abatacept infusions were generally well tolerated. Acute infusion-related reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III trials. Integrated safety data from five clinical trials showed that serious adverse events were reported in 13.6% of abatacept and 12.3% of placebo recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept administered with background biologic DMARDs appears to be less well tolerated than abatacept plus background nonbiologic DMARDs.

6. England 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. [2016] To investigate the efficacy and safety of abatacept for treating patients with rheumatoid arthritis (RA) in routine clinical practice.

7. Germany pubmed.ncbi.nlm.nih.gov

Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study. [2021] Evaluate abatacept retention over 2 years in the AbataCepT In rOutiNe clinical practice (ACTION) study.

8. Germany 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. [2020] AbataCepT In rOutiNe clinical practice (ACTION; NCT02109666) was an observational study of patients with rheumatoid arthritis who initiated intravenous abatacept in clinical practice. We aimed to compare abatacept retention rates and clinical outcomes in patients from Germany versus other countries.