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

Last updated: August 20, 2024
Sponsor: University Hospital, Antwerp
Overall Status: Active - Recruiting

Phase

4

Condition

Kidney Transplantation

Treatment

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

Clinical Study ID

NCT06493526
UZA-6402
  • Ages > 18
  • All Genders

Study 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?

Eligibility Criteria

Inclusion

Inclusion Criteria:

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 transplantbetween 3 and 12 months before screening. ((mis)matching based on the broadEurotransplant Match determinant for DQA1 and on the split Eurotransplant Matchdeterminant 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 tolatest Banff criteria (excl. borderline lesions)

  • Recent assessment of CNI and MPA AUC (performed at least 8 weeks aftertransplantation, but <12 weeks before screening, )

  • Recent OGTT in patients not on antidiabetic therapy (<3 months ago)

Exclusion

Exclusion Criteria:

  • 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 andcortico-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 ororal medi-cation

  • Active peptic ulcer disease

  • Active hepatitis B, hepatitis C or human immunodeficiency virus infection at the dayof trans-plantation

  • New diagnosis of malignancy since transplantation, except successfully treatednonmetastatic basal or squamous cell carcinoma of the skin

  • Pregnancy or lactation

  • Patients unwilling to use reliable anticonception during the study (Male patients ortheir untreated female partner must use reliable contraception during my-cophenolatetreatment and for at least 90 days after stopping MMF treatment. Female patients whocan get pregnant must use at least one reliable form of contraception before, duringand for 6 weeks after stopping MMF treatment)

Study Design

Total Participants: 20
Treatment Group(s): 1
Primary Treatment: Withdrawal of calcineurin-inhibitor, continue on concentration-controlled mycophenolate mofetil and corticosteroids.
Phase: 4
Study Start date:
August 20, 2024
Estimated Completion Date:
June 30, 2027

Study Description

In summary, this pilot, prospective, single-arm open interventional study the investigators will include immune-quiescent zero-DQ mismatched kidney transplant recipients between 3-12 months post-transplant who are on a CNI-based regimen with corticosteroids and MMF. After optimization of MMF dose, targeted at an MPA AUC12 of 60 (±15) mg.h/L, CNIs will be tapered and stopped over a 4 week peri-od. Prednisolon dose will be temporarily increased to 10 mg/day at the day of CNI withdrawal for 14 days, and continued at 5 mg/d thereafter. The primary outcome is biopsy-proven rejection at 6 months after CNI withdrawal. Secondary outcomes will look at other markers of alloreactivity (dnD-SA without clinical or histological signs of rejection), tolerability of MMF in the defined range, infec-tious complications, and possible favorable effects of CNI withdrawal (on GFR, tubular function, blood pressure, lipid profile and diabetes).

Connect with a study center

  • University Hospital Antwerp

    Edegem, Antwerp 2650
    Belgium

    Active - Recruiting

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