DARA-MVI Study (Daratumumab for Microvascular Inflammation in Kidney Transplantation) (DARA-MVI)
A Randomized Controlled Study of Daratumumab for Microvascular Inflammation (MVI) in Kidney Transplant Recipients With or Without Donor-Specific Antibodies
Study Overview
Status
Intervention / Treatment
Detailed Description
Microvascular inflammation (MVI) is a histologic feature associated with antibody-mediated injury and poor long-term graft outcomes in kidney transplantation. However, the optimal management of MVI-particularly in C4d-negative, donor-specific antibody (DSA)-negative cases-remains undefined. Recent data suggest that activation of plasma cells and long-lived memory B cells may contribute to persistent endothelial injury even in the absence of circulating DSA.
Daratumumab, a human monoclonal antibody targeting CD38, has demonstrated potent depletion of plasma cells and immunomodulatory effects in autoimmune diseases and in early reports of antibody-mediated rejection (ABMR) resistant to standard therapy. Building on this evidence, the DARA-MVI study aims to evaluate whether daratumumab can attenuate microvascular inflammation and stabilize graft function in kidney transplant recipients with biopsy-proven MVI but negative C4d staining.
This is a prospective, randomized, open-label, controlled trial enrolling adult kidney transplant recipients who undergo indication or surveillance biopsy revealing MVI (glomerulitis [g] and/or peritubular capillaritis [ptc] ≥ 1). Participants will be randomized in a 1:1 ratio to receive either (1) daratumumab subcutaneous therapy (1800 mg monthly for 3 months) or (2) observation under standard clinical monitoring. A non-randomized reference group of biopsy-negative, DSA-negative, and dd-cfDNA-negative transplant recipients will serve as a comparative baseline for biomarker trajectories.
All participants will undergo structured follow-up for 12 months, including serial assessment of graft function, dd-cfDNA (fraction and copy number), and DSA at baseline and every 3 months. Repeat biopsy at 12 months will evaluate histologic response (change in Banff MVI score: g + ptc).
The primary objective is to determine whether daratumumab reduces microvascular inflammation compared to observation. Secondary objectives include evaluation of changes in donor-derived cell-free DNA, emergence or resolution of DSA, estimated glomerular filtration rate (eGFR), and safety outcomes (adverse events, infection, and cytopenia).
The study also aims to explore correlations between histologic, molecular (dd-cfDNA), and serologic (DSA) indicators of alloimmune activity. This will help determine whether daratumumab can interrupt subclinical alloimmune injury and delay chronic graft deterioration.
If successful, this study could define a novel therapeutic approach for antibody-independent microvascular inflammation and clarify the role of plasma-cell-directed therapies in complex post-transplant immune responses.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Martin, Slovakia, 036 01
- Transplant-nephrology department
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion:
Age ≥ 18, kidney transplant recipients (first or higher, living or deceased donor), biopsy-proven MVI (g ≥ 1 and/or ptc ≥ 1), C4d-negative, DSA-negative (Cohort 1) or DSA-positive (Cohort 2), informed consent.
Exclusion:
C4d-positive biopsy, active TCMR ≥ IA, infection or malignancy, multi-organ transplant, prior anti-CD38 therapy, pregnancy, breastfeeding.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Experimental: Daratumumab (Darzalex®)
Participants with biopsy-proven microvascular inflammation (MVI) (Banff g ≥1 and/or ptc ≥1), C4d-negative, randomized to receive daratumumab 1800 mg SC once monthly for 3 months, in addition to standard post-transplant care and monitoring (DSA, dd-cfDNA, eGFR).
|
Daratumumab 1800 mg subcutaneously once monthly × 3 doses plus standard monitoring of DSA and dd-cfDNA every 3 months.
Other Names:
|
|
Active Comparator: Active Comparator: Observation (Standard Care)
Participants with biopsy-proven MVI, C4d-negative, randomized to observation under standard post-transplant care and monitoring (DSA, dd-cfDNA, eGFR) without daratumumab treatment.
|
Standard post-transplant management and monitoring per institutional protocol.
Includes serial measurement of DSA and donor-derived cell-free DNA every 3 months, eGFR monitoring, and repeat biopsy at 12 months.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Primary Outcome: Change in microvascular inflammation score (Banff g + ptc) between baseline and 12 months.
Time Frame: Baseline (study entry) and 12 months after randomization
|
The composite microvascular inflammation (MVI) score, defined as the sum of glomerulitis (g) and peritubular capillaritis (ptc) scores according to the Banff classification (range 0-6), will be assessed on kidney-allograft biopsy specimens obtained at baseline and at 12 months.
The change in total MVI score (ΔMVI = [g + ptc]₁₂ₘ - [g + ptc]₀) will be compared between treatment arms to evaluate the effect of daratumumab on microvascular inflammation.
|
Baseline (study entry) and 12 months after randomization
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TNO DARA MVI
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.