Assessment of Biomarker-Guided CNI Substitution In Kidney Transplantation

NCT05917522 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT RTB-015
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 15

Brief Summary

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).

Conditions

Kidney Transplant

Keywords

Kidney Transplant; Abatacept; HLA-DR/DQ mMM

Outcome Measures

Primary Outcomes (2)

• In the Observational Study - The occurrence of any alloimmune event

  including de novo Donor Specific Antibody (DSA), any Biopsy Proven Acute Rejection (BPAR) (Banff borderline or greater, on a for-cause or the 6-month post-transplant protocol biopsy) and censored by non-alloimmune graft failure or death with function or lost-to-follow up.

  Up to 24 months post-Kidney Transplant

• In the Nested Randomized Control Trial (RCT) - Renal function, measured as the difference in eGFRCKD-EPI at 24-months between groups (adjusted for renal function at randomization).

  At 18 months post-randomization (24 months post-transplant)

Secondary Outcomes (3)

• In the Observational Study - The occurrence of any alloimmune event

  At 24 months post-Kidney Transplant (post-kidney transplant)

• In the Nested Randomized Control Trial (RCT) - Composite neurocognitive function (NIH-Toolbox Cognitive Battery) score

  At 18-mo post-randomization

• In the Nested Randomized Control Trial (RCT) - Biopsy Proven Acute Rejection (BPAR) efficacy failure

  From randomization to 18-mo post-randomization

Study Arms (3)

Observational Study - Full Cohort

NO 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.

Nested RCT - Treatment Group (Abatacept)

EXPERIMENTAL

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.

Biological: Abatacept

Nested RCT - Control Group (SOC)

ACTIVE COMPARATOR

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.

Procedure: Standard of Care at US Transplant Centers

Interventions

Abatacept BIOLOGICAL

Injection: 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled ClickJect autoinjector

Also known as: Orencia

Nested RCT - Treatment Group (Abatacept)

Standard of Care at US Transplant Centers PROCEDURE

Control group, remaining on SOC (Tacrolimus/ Mycophenolic Acid (MPA)/ Prednisone (Pred))

Nested RCT - Control Group (SOC)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Observational Study:
• Subject must be able to understand and provide informed consent
• Received (within 14 days) or candidate for an ABO-compatible kidney transplant, including A2 to B
• Panel Reactive Antibody \<=60% as determined by local site
• Virtual cross-match negative as determined by local site or Donor Specific Antibody (DSA) negative by central lab within 14 days post-transplant
• Female subjects of childbearing potential must have a negative pregnancy test upon study entry
• All subjects with reproductive potential must agree to use highly effective contraception for the duration of the study (http://www.fda.gov/birthcontrol)
• Hepatitis C Virus Ab positive subjects with negative Hepatitis C Virus polymerase chain reaction (HCV PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission
• Vaccines up to date as per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials (Refer to Manual of Procedures).
• Triple Immunosuppression - Calcineurin Inhibitor/Mycophenolic Acid/Steroid (CNI/MPA/steroid)
• CNI (Tacrolimus (TAC), target trough \[C0\] level: 0-3 mo, 8-12 ng/mL; 4-6 mo, 6-10 ng/mL; \>6 mo, 5-8 ng/mL\])
• MPA \[target dose: mycophenolate mofetil \>=500 mg bid or mycophenolate sodium \>=360 mg bid\]); and
• Glucocorticoid, with a minimum dose equivalent to 5mg of prednisone per day
• Nested Randomized Control Trial (RCT):
• Subject must be able to understand and provide informed consent

You may not qualify if:

• Observational Study:
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol including a mandated 6-mo kidney transplant biopsy
• Non-Kidney Transplant (KTx) (pre-existing or concurrent)
• Current use of immunomodulatory agents (including but not limited to: Rituximab, anti-Tumor necrosis factor(TNF) Monoclonal antibodies (mAb), or Belatacept, abatacept, Janus kinase inhibitors)
• Transplant in which the kidney donor is the recipient's Identical twin
• Epstein-Barr virus (EBV) sero-negative KTx recipient
• Chronic obstructive pulmonary disease (COPD)
• Untreated Latent Tuberculosis (TB)
• Human immunodeficiency virus (HIV) infection
• Active Hepatitis B infection (HBsAg+ or anti-HBcore +)
• Enrollment in another investigational trial
• Current, diagnosed, mental illness or current, diagnosed or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
• Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
• Use of investigational drugs within 8 weeks of participation
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (15)

University of Alabama School of Medicine: Transplantation

Birmingham, Alabama, 35233, United States

RECRUITING

Cedars Sinai Medical Center: Transplantation

Los Angeles, California, 90048, United States

RECRUITING

Ronald Reagan UCLA Medical Center: Transplantation

Los Angeles, California, 90095, United States

RECRUITING

Yale University, School of Medicine: Transplantation

New Haven, Connecticut, 06519, United States

RECRUITING

Johns Hopkins Hospital:Transplantation

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital: Transplantation

Boston, Massachusetts, 02114, United States

RECRUITING

Mayo Clinic Rochester: Transplantation

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

University of Nebraska Medical Center: Transplantation

Omaha, Nebraska, 68198, United States

RECRUITING

Duke University Medical Center: Transplantation

Durham, North Carolina, 27710, United States

RECRUITING

Cleveland Clinic Foundation: Transplantation

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

University of Pennsylvania Medical Center: Transplantation

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh Medical Center: Transplantation

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

University of Virginia Health System: Transplantation

Charlottesville, Virginia, 22908, United States

RECRUITING

University of Wisconsin School of Medicine and Public Health: Transplantation

Madison, Wisconsin, 53726, United States

NOT YET RECRUITING

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Description Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Interventions

Abatacept

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Peter S Heeger, M.D.

  Cedars Sinai Medical Center: Transplantation

  STUDY CHAIR

• Peter Nickerson, M.D.

  University of Manitoba Max Rady College of Medicine - Transplantation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: June 26, 2023
• Study Start: December 7, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial
• Access Criteria: Open access

Locations

US (15)