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

The DARA-MVI Study is a prospective, randomized, controlled, open-label trial designed to evaluate the effect of daratumumab on microvascular inflammation (MVI) in kidney transplant recipients with C4d-negative biopsies. Participants with biopsy-proven MVI will be randomized to receive either daratumumab or observation with standard monitoring. The study will assess changes in histologic MVI score, donor-derived cell-free DNA (dd-cfDNA), donor-specific antibodies (DSA), and graft function over 12 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Microvascular Inflammation - MVI in Kindey Transplant Recipients
• Intervention / Treatment: Drug: DARATUMUMAB (DARZALEX®); Other: Observation (Standard Care)

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: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Slovakia
  • Martin, Slovakia, 036 01
    • Transplant-nephrology department

Participation Criteria

Eligibility Criteria

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

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)

Number of Arms

2

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).	Drug: DARATUMUMAB (DARZALEX®); Daratumumab 1800 mg subcutaneously once monthly × 3 doses plus standard monitoring of DSA and dd-cfDNA every 3 months.; Other Names: Experimental: Daratumumab (Darzalex®)
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.	Other: Observation (Standard Care); 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: Active Comparator: Observation (Standard Care)

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.	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: University Hospital, Martin

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Kidney transplantation; acute rejection; Microvascular inflammation
• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Investigative Techniques; Methods; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; Observation; daratumumab
• Other Study ID Numbers: TNO DARA MVI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the published results will be made available upon reasonable request from qualified researchers after publication, following institutional and ethical approval. Supporting documents (protocol, statistical analysis plan) may also be shared.
• IPD Sharing Time Frame: from 01/MAR/2025 for 20 years
• 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: No
• Studies a U.S. FDA-regulated device product: No