Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients (OPTIMA-KT)

Optimizing Immunosuppression in Low-Risk Older Adult Kidney Transplant Recipients (OPTIMA-KT): A Prospective, Randomized, Open-Label, Blinded-Endpoint Single-Site Pilot/Feasibility Trial of Biomarker-Guided Mycophenolate Mofetil Elimination

Most kidney transplant recipients take a combination of anti-rejection medicines for the rest of their life. One of these is called mycophenolate mofetil (MMF), also known by the brand name CellCept. While MMF helps protect the kidney, taking it for many years can cause infections, low blood counts, stomach problems, and a higher risk of certain cancers, problems that older adults are especially likely to experience.

We are doing this study to learn whether carefully and slowly stopping MMF in older adults who are doing well after their transplant is as safe as continuing MMF, when we use blood and urine tests to closely watch for any early signs of trouble. The information learned could help future kidney transplant patients use less medicine without losing their transplant.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant Recipient
• Intervention / Treatment: Drug: Tacrolimus (Kidney transplant maintenance immunosuppression); Drug: Mycophenoate Mofetil; Drug: Prednisone (SOC arm); Drug: Prednisone (MMF Elimination arm)

Detailed Description

To evaluate the feasibility, safety, protocol adherence, biomarker monitoring completion, and preliminary clinical event rates associated with stepwise MMF elimination over 6 months compared with standard-of-care immunosuppression in low-risk older adult kidney transplant recipients.

Secondary objectives. To compare between arms: eGFR trajectory and proteinuria at Months 6 and 12; infection incidence (including CMV and BK), hospitalization, and adverse drug events; de novo DSA incidence and time to de novo DSA; and the kinetics and predictive performance of dd-cfDNA and urine CXCL9 and CXCL10 for rejection and de novo DSA.

Exploratory objectives. To assess the association between PIRCHE-II score and individual primary endpoint components; the performance of combined biomarker panels versus single biomarkers; health-related quality of life and patient-reported outcomes through Month 12; and cost and healthcare resource utilization through Month 12 across study arms.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Amber Paulus, PhD; Phone Number: (804) 827-1743; Email: amber.paulus@vcuhealth.org
• Study Contact Backup: Name: Natalie Kilmarx; Phone Number: (804) 828-7522; Email: natalie.salsini@vcuhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Greater than 60 years of age
• Greater than 12 months from kidney transplant
• Stable maintenance tacrolimus- based immunosuppression for at least 3 months without dose changes greater than 25%
• PIRCHE-II score less than or equal to 65 calculated from available donor and recipient HLA typing
• Ability to provide written informed consent and comply with study procedures

Exclusion Criteria:

• Multi-organ transplant or prior graft loss due to rejection
• Maintenance immunosuppression including belatacept, cyclosporine, azathioprine, sirolimus, or other agents in lieu of tacrolimus or MMF
• Steroid-free regimen
• Active malignancy (excluding non-melanoma skin cancer)
• Uncontrolled infection
• BK viremia greater than 10,000 copies/mL, or BK nephropathy
• High immunologic risk (any preformed DSA, positive crossmatch, or biopsy-proven rejection within the prior 6 months)
• Pregnancy, breastfeeding, self-reported pregnancy, positive pregnancy test during screening if testing is indicated, or inability/unwillingness to comply with required pregnancy prevention measures if of childbearing potential
• Inability to comply with study procedures including monthly visits and biospecimen collection
• Concurrent participation in another conflicting interventional trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Participants continue tacrolimus-based maintenance immunosuppression (tacrolimus, MMF, with or without prednisone)	Drug: Tacrolimus (Kidney transplant maintenance immunosuppression); Administration of Tacrolimus; Drug: Mycophenoate Mofetil; Participants are administered MMF; Drug: Prednisone (SOC arm); Participants in SOC arm may be administered Prednisone as indicated
Experimental: MMF Elimination (Mycophenolate Mofetil ); Mycophenolate Mofetil (MMF) is reduced to approximately 50% of baseline daily dose at Month 1, approximately 25% at Month 2, and discontinued at Month 3, remaining discontinued through Month 6 unless biomarker triggers prompt reinstatement. Tacrolimus trough is maintained at 5 to 8 ng/mL with monthly monitoring and coefficient of variation tracking; prednisone is continued at site-standard dose unless contraindicated.	Drug: Tacrolimus (Kidney transplant maintenance immunosuppression); Administration of Tacrolimus; Drug: Mycophenoate Mofetil; Participants are administered MMF; Drug: Prednisone (MMF Elimination arm); Participants in the MMF Elimination arm may be administered prednisone as indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of MMF Elimination	Proportion of eligible participants enrolled and retained through completion of the intervention	6 months
Protocol Adherence	Proportion of participants completing the assigned treatment strategy without major protocol deviations	6 months
Biomarker Monitoring Completion	Proportion of scheduled biomarker assessments successfully completed.	6 months
Clinical Composite Event Rate	Time to first occurrence of all-cause death, graft loss, biopsy-proven rejection, major infection requiring IV therapy or hospitalization, graft-related hospitalization, or confirmed de novo donor-specific antibody.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare estimated glomerular filtration rate (eGFR) trajectory at Months 6 and 12	Compare estimated glomerular filtration rate (eGFR) trajectory at Months 6 and 12.	Months 6 and 12
Compare Urine Protein-to-Creatinine Ratio (UPCR) Between Arms at Months 6 and 12	Compare Urine Protein-to-Creatinine Ratio (UPCR) Between Arms at Months 6 and 12.	Months 6 and 12
Comparison of Infection incidence	Number of participants experiencing one or more infections	Months 6 and 12
Comparison of Participants Hospitalized	Number of participants experiencing one or more hospitalizations	Months 6 and 12
Comparison of Total Hospitalizations	Total number of hospitalizations across all participants	Months 6 and 12
Comparison of adverse events	Number of participants experiencing one or more adverse events	Months 6 and 12
Comparison of serious adverse events	Number of participants experiencing one or more serious adverse events	Months 6 and 12
De Novo Donor-Specific Antibody Incidence	Number of participants who develop confirmed de novo donor-specific antibodies after randomization	Month 12
Time to De Novo Donor-Specific Antibody	Time from randomization to first confirmed de novo donor-specific antibody	Month12
Donor-Derived Cell-Free DNA (dd-cfDNA)	Longitudinal change in dd-cfDNA and its predictive performance for rejection and de novo donor-specific antibody	Month 12
Urine CXCL9 Concentration (pg/mL)	Longitudinal change in urine CXCL9 and its predictive performance for rejection and de novo donor-specific antibody	Month 12
Urine CXCL10 Concentration (pg/mL)	Longitudinal change in urine CXCL10 and its predictive performance for rejection and de novo donor-specific antibody	Month 12

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Amber Paulus, PhD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: August 18, 2026
• First Submitted That Met QC Criteria: August 31, 2026
• First Posted (Actual): September 8, 2026

Study Record Updates

• Last Update Posted (Actual): September 8, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Macrolides; Lactones; Pregnadienediols; Prednisone; Tacrolimus
• Other Study ID Numbers: HM300000943

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual participant data supporting the published results will be available beginning after publication of the primary results and for 10 years after study completion. Access will require investigator approval, IRB approval when applicable, and a data use agreement
• IPD Sharing Time Frame: 10 years after study completion
• IPD Sharing Access Criteria: Access will require investigator approval, IRB approval when applicable, and a data use agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No