Mycophenolate-Based Therapy for Kidney Transplant Recipients Without HLA-DQ Mismatch

NCT06493526 | Recruiting Phase 4

• 1 other identifier: UZA-6402
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if calcineurin-inhibitor therapy (a drug commonly used to prevent rejection) can be safely stopped in kidney transplant recipients with a relatively low risk of rejection (being recipients of a first transplant, without any signs of pre-existing immunity against the graft, and having a good HLA match with the donor (no mismatch in HLA-DQ)). Before stopping the calcineurin-inhibitors, the remaining therapy with mycophenolate mofetil and corticosteroids will be optimized.The main questions it aims to answer are: Is this approach safe, in terms of preventing rejection? Is this approach well tolerated? Will this approach lead to better kidney function and/or other beneficial effects?

Conditions

Kidney Transplantation

Keywords

mycophenolate mofetil; Calcineurin Inhibitor; calcineurin inhibitor withdrawal; HLA-DQ; rejection; area under the curve; withdrawal; pharmacokinetic; concentration-controlled; mismatches

Outcome Measures

Primary Outcomes (1)

• Incidence of biopsy proven rejection

  Biopsy will be performed as clinically indicated, or in case DSA develop (directed against HLA -A, HLA-B, HLA-DR or HLA-DQ with a MFI \> 500 and remaining present in a repeated test after 6 weeks (± 2 weeks)) to exclude subclinical rejection.

  at 26 weeks after CNI withdrawal

Secondary Outcomes (20)

• Incidence of biopsy proven rejection

  at 14 weeks and 1 year after CNI withdrawal

• Incidence of de novo donor specific HLA antibodies (dnDSA)

  at 14 weeks, 26 weeks and 1 year after CNI withdrawal

• Tolerability of MMF in the defined range

  up to 1 year after CNI withdrawal

• Change in eGFR

  Comparing day 0 (day of CNI withdrawal) to 14 weeks, 26 weeks and 1 year after CNI withdrawal

• Change in creatinine clearance

  Comparing day 0 (day of CNI withdrawal) to 14 weeks, 26 weeks and 1 year after CNI withdrawal

Study Arms (1)

Withdrawal of calcineurin-inhibitors in zero-HLA DQ-mismatched kidney transplant recipients

EXPERIMENTAL

calcineurin-inhibitor withdrawal, continue on a concentration controlled mycophenolate dose (AUC12 target 60 h.mg/L)

Drug: Withdrawal of calcineurin-inhibitor, continue on concentration-controlled mycophenolate mofetil and corticosteroids.

Interventions

Withdrawal of calcineurin-inhibitor, continue on concentration-controlled mycophenolate mofetil and corticosteroids. DRUG

Mycophenolate mofetil dose will be optimized to an AUC12 of 60 h.mg/L, thereafter the calcineurin inhibitor will be withdrawn.

Withdrawal of calcineurin-inhibitors in zero-HLA DQ-mismatched kidney transplant recipients

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Adults ≥ 18 years old who received a first, zero-HLA-DQ mismatched kidney transplant between 3 and 12 months before screening. ((mis)matching based on the broad Eurotransplant Match determinant for DQA1 and on the split Eurotransplant Match determinant for DQB1
• Maintenance immunosuppressive therapy should consist of a calcineurin-inhibitor (tacrolimus or cyclosporine), MMF and corticosteroids
• subjects capable of giving informed consent
• eGFR ≥ 20 ml/min/1.73m² based on CKD-EPI Creatinine-Cystatin Equation at screening
• Recent HLA antibody testing (\<6 weeks before screening)
• Absence of DSA (MFI \> 500) at screening and in all historical samples
• Absence of subclinical rejection on a protocol kidney transplant biopsy according to latest Banff criteria (excl. borderline lesions)
• Recent assessment of CNI and MPA AUC (performed at least 8 weeks after transplantation, but \<12 weeks before screening, )
• Recent OGTT in patients not on antidiabetic therapy (\<3 months ago)

You may not qualify if:

• Receipt of a non-renal transplant
• HLA identical sibling donor transplant
• ABO incompatible kidney transplantation
• cdc-PRA at transplantation \> 50%
• Ongoing treatment with immunosuppressive drugs other than CNI, MMF/MPA and cortico-steroids
• Prophylactic therapy with valganciclovir
• History of biopsy-proven acute rejection
• Unexplained rise in creatininemia \>20% over the last 6 weeks
• Albuminuria \> 1g/day ( based on latest 24h urine collection max 6 weeks ago)
• Chronic diarrhea or gastrointestinal disorders that interfere with the absorption or oral medi-cation
• Active peptic ulcer disease
• Active hepatitis B, hepatitis C or human immunodeficiency virus infection at the day of trans-plantation
• New diagnosis of malignancy since transplantation, except successfully treated nonmetastatic basal or squamous cell carcinoma of the skin
• Pregnancy or lactation
• Patients unwilling to use reliable anticonception during the study (Male patients or their untreated female partner must use reliable contraception during my-cophenolate treatment and for at least 90 days after stopping MMF treatment. Female patients who can get pregnant must use at least one reliable form of contraception before, during and for 6 weeks after stopping MMF treatment)

Sponsors & Collaborators

• University Hospital, Antwerp: lead

Study Sites (1)

University Hospital Antwerp

Edegem, Antwerp, 2650, Belgium

RECRUITING

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Rachel Hellemans, MD PhD

  Antwerp University Hospital, Department of Nephrology, Drie Eikenstraat 655, 2650 Edegem, BELGIUM

  PRINCIPAL INVESTIGATOR

• Hans de Fijter, MD PhD

  Antwerp University Hospital, Department of Nephrology, Drie Eikenstraat 655, 2650 Edegem, BELGIUM

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Hellemans, MD PhD

CONTACT

+3238213435; rachel.hellemans@uza.be

Hans de Fijter, MD PhD

CONTACT

+3238213435; nefrologie@uza.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: July 10, 2024
• Study Start: August 20, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)