Ignite Creation Date:
2024-05-06 @ 7:08 PM
Last Modification Date:
2024-10-26 @ 3:01 PM
Study NCT ID:
NCT05917522
Status:
RECRUITING
Last Update Posted:
2024-02-08
First Post:
2023-05-11
Brief Title:
Assessment of Biomarker-Guided CNI Substitution In Kidney Transplantation
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
Assessment of Biomarker-Guided Calcineurin Inhibitor CNI Substitution In Kidney Transplantation RTB-015
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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-DRDQ 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 21 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-DRDQ 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
The primary objective of the Observational Study is to test the validity of the HLA-DRDQ 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
Detailed Description:
Observational Study
Enrolling 800 adult first time kidney transplant recipients Consent and enrollment will be targeted to occur pre- or post-kidney transplant during the initial hospitalization All subjects enrolled in the study will be followed observationally to evaluate HLA-DRDQ molecular mismatched mMM as a risk-stratifying prognostic biomarker
This prospective multi-center observational study of 800 kidney transplant recipients at clinically low risk for alloimmune memory DSA negative pre-kidney transplant who are initiated on standard of care SOC therapy will be used to satisfy the FDA requirement to prospectively evaluate the HLA mMM score as a prognostic biomarker for post-kidney transplant outcomes in a real-world cohort Donor-recipient HLA-DRDQ mMM score will be determined at enrollment and recipients will be followed over 24 months post- kidney transplant for primary alloimmune events ie T cell Mediated Rejection TCMR DSA and Antibody Mediated Rejection ABMR
Nested RCT SOC versus conversion to abatacept
We will follow subjects in the Observational Study for the initial 6 months to identify those who meet the stringent immune-quiescent randomization criteria absence of biopsy proven acute rejection BPAR on a for-cause or 6-month surveillance biopsy and absence of DSA In addition these subjects must have absence of infection eg BKVCMV and be on at least MMF 500 mg po bid at the time of randomization From this immune-quiescent group those individuals with a low or intermediate HLA-DRDQ mMM score will be eligible for the Nested RCT
300 eligible subjects will be randomized 21 to abatacept or SOC in the randomization phase Abatacept arm 200 vs SOC arm 100 to have adequate power for detecting differences between the treatment groups Subjects enrolled into the trials screening phase 0-6 months post-transplant of the Observational Study will identify at least 360 kidney transplant recipients who exhibit immune quiescence and who meet the 6-months post-kidney transplant eligibility criteria for the Nested RCT These individuals will be re-consented prior to randomization at 6-months post-kidney transplant
Enrolling 800 adult first time kidney transplant recipients Consent and enrollment will be targeted to occur pre- or post-kidney transplant during the initial hospitalization All subjects enrolled in the study will be followed observationally to evaluate HLA-DRDQ molecular mismatched mMM as a risk-stratifying prognostic biomarker
This prospective multi-center observational study of 800 kidney transplant recipients at clinically low risk for alloimmune memory DSA negative pre-kidney transplant who are initiated on standard of care SOC therapy will be used to satisfy the FDA requirement to prospectively evaluate the HLA mMM score as a prognostic biomarker for post-kidney transplant outcomes in a real-world cohort Donor-recipient HLA-DRDQ mMM score will be determined at enrollment and recipients will be followed over 24 months post- kidney transplant for primary alloimmune events ie T cell Mediated Rejection TCMR DSA and Antibody Mediated Rejection ABMR
Nested RCT SOC versus conversion to abatacept
We will follow subjects in the Observational Study for the initial 6 months to identify those who meet the stringent immune-quiescent randomization criteria absence of biopsy proven acute rejection BPAR on a for-cause or 6-month surveillance biopsy and absence of DSA In addition these subjects must have absence of infection eg BKVCMV and be on at least MMF 500 mg po bid at the time of randomization From this immune-quiescent group those individuals with a low or intermediate HLA-DRDQ mMM score will be eligible for the Nested RCT
300 eligible subjects will be randomized 21 to abatacept or SOC in the randomization phase Abatacept arm 200 vs SOC arm 100 to have adequate power for detecting differences between the treatment groups Subjects enrolled into the trials screening phase 0-6 months post-transplant of the Observational Study will identify at least 360 kidney transplant recipients who exhibit immune quiescence and who meet the 6-months post-kidney transplant eligibility criteria for the Nested RCT These individuals will be re-consented prior to randomization at 6-months post-kidney transplant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None