Microvascular Inflammation - MVI in Kindey Transplant RecipientsPhase 4DARA-MVINCT07274462
DARA-MVI Study (Daratumumab for Microvascular Inflammation in Kidney Transplantation)
A Phase 4 study testing DARATUMUMAB (DARZALEX®) in people with Microvascular Inflammation - MVI in Kindey Transplant Recipients, run by University Hospital, Martin at 1 site in Slovakia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Microvascular Inflammation - MVI in Kindey Transplant Recipients
- What is being tested?
- DARATUMUMAB (DARZALEX®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSlovakia
- Study dates
- 1 Nov 2025to 30 Sep 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- C4d-positive biopsy, active TCMR ≥ IA, infection or malignancy, multi-organ transplant, prior anti-CD38 therapy, pregnancy, breastfeeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- DARATUMUMAB (DARZALEX®), Observation (Standard Care)
- Keywords
- Kidney transplantation, Microvascular inflammation, acute rejection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DARATUMUMAB (DARZALEX®)Drug
Also called Experimental: Daratumumab (Darzalex®)
Daratumumab 1800 mg subcutaneously once monthly × 3 doses plus standard monitoring of DSA and dd-cfDNA every 3 months.
Observation (Standard Care)Other
Also called Active Comparator: 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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Daratumumab (Darzalex®) | Experimental | 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). Receives: Drug: DARATUMUMAB (DARZALEX®) |
| Active Comparator: Observation (Standard Care) | Active comparator | Participants with biopsy-proven MVI, C4d-negative, randomized to observation under standard post-transplant care and monitoring (DSA, dd-cfDNA, eGFR) without daratumumab treatment. Receives: Other: Observation (Standard Care) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (study entry) and 12 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2025
- Study start1 Nov 2025
- Primary completion1 Mar 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Microvascular Inflammation - MVI in Kindey Transplant RecipientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Martin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matej Vnucak, University Hospital, Martin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07274462
- Sponsor's protocol ID
- TNO DARA MVI
- Acronym
- DARA-MVI
- Status last verified
- Nov 2025
- First submitted
- 27 Nov 2025
- Last updated
- 10 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Study of Daratumumab for Microvascular Inflammation (MVI) in Kidney Transplant Recipients With or Without Donor-Specific Antibodies
- ClinicalTrials.gov ID
- NCT07274462
- Acronym / sponsor ID
- DARA-MVI / TNO DARA MVI
- Keywords
- Kidney transplantation, Microvascular inflammation, acute rejection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital, MartinUniversity, hospital or other
- Study start
- 1 Nov 2025 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 10 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental: Daratumumab (Darzalex®) | Experimental | Drug: 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). |
| Active Comparator: Observation (Standard Care) | Active comparator | Other: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- C4d-positive biopsy, active TCMR ≥ IA, infection or malignancy, multi-organ transplant, prior anti-CD38 therapy, pregnancy, breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DARATUMUMAB (DARZALEX®)Also: Experimental: Daratumumab (Darzalex®)Daratumumab 1800 mg subcutaneously once monthly × 3 doses plus standard monitoring of DSA and dd-cfDNA every 3 months. | Drug | Experimental: Daratumumab (Darzalex®) |
| Observation (Standard Care)Also: Active Comparator: 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 | Active Comparator: Observation (Standard Care) |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
- Individual participant dataSharing planned: Yes. 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing DARATUMUMAB (DARZALEX®) in people with Microvascular Inflammation - MVI in Kindey Transplant Recipients, run by University Hospital, Martin at 1 site in Slovakia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2025.