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CompletedNCT04112810Updated Oct 21, 2025Results posted

Tildrakizumab for Prevention of Acute Graft-Versus-Host Disease

A Phase 2 interventional study of Tildrakizumab in Hematologic Malignancies, sponsored by Medical College of Wisconsin. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-10-21.

Sponsored by Medical College of Wisconsin · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
51
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This is a phase 2 open-label trial designed to evaluate the efficacy of tildrakizumab in improving graft-versus-host disease (GVHD)-free relapse-free survival after myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.

Read the detailed description

Study Rationale: GVHD remains a major cause of morbidity and mortality following myeloablative conditioning (MAC) alloHCT. Proinflammatory cytokines play a central role in initiation and development of acute GVHD and as such, inhibition of these cytokines has been examined for both prevention and treatment of GVHD. Interleukin (IL)-23 is a proinflammatory cytokine which the investigators' lab has shown to have a unique and selective role in induction of colonic inflammation during acute GVHD and that this cytokine serves as a critical mediator linking conditioning regimen-induced mucosal injury and endotoxin lipopolysaccharide (LPS) translocation to subsequent proinflammatory cytokine production and GVHD-associated pathological damage. Moreover, additional studies have demonstrated that blocking the IL-23 signaling pathway has not abrogated the graft-versus-tumor effect. Tildrakizumab is a commercially available anti-IL-23 antibody FDA approved for the treatment of moderate to severe psoriasis with good tolerance. The investigators hypothesize that blocking IL-23, with tildrakizumab, will reduce GVHD rates for patients undergoing MAC alloHCT without having an impact on relapse rates, thus improving GVHD-free relapse-free survival (GRFS).

02

Conditions studied

  • Hematologic Malignancies

Keywords

  • Graft-versus-host disease
03

In context

Hematologic Neoplasms

1,464 studies on the registry are indexed under Hematologic Neoplasms; 433 are open to participants now.

This study's enrollment of 51 is above the median of 45 across 1,068 interventional studies indexed under Hematologic Neoplasms.

Browse Hematologic Neoplasms studies →

Lead sponsor

Medical College of Wisconsin is the lead sponsor of 540 studies on the registry; 120 are open to participants now.

Of its 71 completed or terminated interventional studies of FDA-regulated products, 56 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age ≥18 years.
  2. Patients with any hematologic malignancy for which alloHCT is indicated. Patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) must be in complete remission at the time of alloHCT (\<5% blasts in the bone marrow, normal maturation of all cellular components in the bone marrow and absence of extramedullary disease). Patients with myelodysplastic syndrome (MDS) must have \<10% blasts in the bone marrow, no circulating blasts.
  3. Myeloablative conditioning (MAC) regimen, based on Center for International Blood and Marrow Transplant Research (CIBMTR) criteria (total body irradiation (TBI) ≥5 Gy single dose or ≥8 Gy fractionated or busulfan [Bu] dose >8 mg/kg oral or >6.4 mg/kg intravenous).
  4. T cell-replete peripheral blood graft.
  5. Patients must have a matched related or unrelated donor (at least 6/6 match at human leukocyte antigen (HLA) -A, -B and -C for related donors and at least 8/8 match at HLA -A, -B, -C and -DRB1 for unrelated donors).
  6. Cardiac function: Left ventricular ejection fraction ≥45% for myeloablative conditioning.
  7. Estimated creatinine clearance ≥40 mL/minute (using the Cockcroft-Gault formula and actual body weight).
  8. Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% (adjusted for hemoglobin) and forced expiratory volume in 1 second (FEV1) ≥50%.
  9. Liver function: total bilirubin \<3 x upper limit of normal and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \<5 x upper normal limit.

  10. Female subjects must meet one of the following:

    Postmenopausal for at least one year before enrollment, OR

    1. Surgically sterile (i.e. undergone a hysterectomy or bilateral oophorectomy), OR
    2. If subject is of childbearing potential (defined as not satisfying either of the above two criteria), she must agree to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 90 days after the last dose of study agent, OR
    3. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable contraception methods.)

  11. Male subjects, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:

    1. Practice effective barrier contraception during the entire study period and through 60 calendar days after the last dose of study agent, OR
    2. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable methods of contraception.)
  12. Signed informed consent: Voluntary written consent must be given before patient registration and performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  13. Planned post-transplant maintenance therapy is allowed.
  14. Prior autologous transplant is allowed.

Exclusion criteria

Exclusion Criteria:

  1. Prior allogeneic hematopoietic cell transplant (HCT).
  2. Active central nervous system (CNS) involvement with malignancy.
  3. Patients receiving cord blood or haploidentical allograft.
  4. Patients undergoing in vivo or ex vivo T cell-depleted alloHCT.
  5. Karnofsky Performance Score \<60% or Eastern Cooperative Oncology Group (ECOG) > or = 2.
  6. Patients with uncontrolled bacterial, viral or fungal infections (currently on treatment and with progression of infectious disease or no clinical improvement) at time of enrollment.
  7. Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive.
  8. Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal antibody planned as part of conditioning regimen for GVHD prophylaxis.
  9. Participation in another GVHD prophylaxis clinical trial.
  10. Any current uncontrolled cardiovascular conditions, including uncontrolled ventricular arrhythmias, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, or electrocardiographic evidence of active ischemia or active conduction system abnormalities.
  11. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
51 participants (actual)

Study arms

  • Experimental
    Tildrakizumab

    Tildrakizumab (IluymaTM) is a humanized monoclonal antibody that specifically binds to the IL-23p19 subunit of IL-23 to neutralize its function.

    Drug: Tildrakizumab

Interventions

  • DrugTildrakizumab

    100 mg will be injected subcutaneously on Day -1, Day 28 ± 3, Day 112 ± 7, Day 196 ± 14, and Day 280 ± 14.

    Also known as: Iluyma

06

What researchers measure

Primary outcomes

  1. GVHD-free Relapse-Free Survival

    Number of subjects experiencing any of grade III-IV acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death at 12 months

    Time frame: 1 year

Secondary outcomes

  1. Incidence of Chronic GVHD

    Number of subjects experiencing chronic GVHD defined by NIH Consensus criteria.

    Time frame: Day +180

  2. Incidence of Chronic GVHD

    Number of subjects experiencing chronic GVHD defined by NIH Consensus criteria.

    Time frame: Day +365

  3. Incidence of Acute GVHD

    Number of subjects experiencing grades II-IV and III-IV acute GVHD will be determined at Day +100 and Day +180 post-HCT. Acute GVHD will be graded according to NIH Consensus criteria.

    Time frame: Day +100 and Day +180

  4. Incidence of Acute GI GVHD

    Number of subjects experiencing grades II-IV and III-IV acute GI GVHD will be determined at Day +100 and Day +180 post-HCT. This will be graded according to NIH Consensus criteria.

    Time frame: Day +100 and Day +180

  5. Primary Graft Failure.

    Number of subjects experiencing no neutrophil recovery to \> 500 cells/μL by Day 28 post-HCT.

    Time frame: Day 28

  6. Secondary Graft Failure

    Number of subjects experiencing initial neutrophil engraftment followed by subsequent decline in absolute neutrophil counts \<500 cells/μL, unresponsive to growth factor therapy, but cannot be explained by disease relapse or drugs.

    Time frame: Up to Day 365

  7. Hematopoietic Recovery According to Neutrophil Count Recovery

    This measure is the number of subjects with the event. The number of days to hematopoietic recovery will be assessed according to neutrophil count recovery after hematopoietic stem cell transplant (HSCT). Neutrophil recovery or engraftment is defined as achieving an absolute neutrophil count (ANC) ≥500/mm\^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil engraftment.

    Time frame: Day +28

  8. Hematopoietic Recovery According to Platelet Count Recovery

    This measure is the number of subjects with the event. The number of days to hematopoietic recovery will be assessed according to platelet count recovery after HSCT. Platelet recovery is defined by either the first day of a sustained platelet count \>20,000/mm\^3 for three days with no platelet transfusion in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment.

    Time frame: Day +28

  9. Non-relapsed Mortality.

    Number of subjects who die after alloHCT without experiencing a relapse.

    Time frame: Day +100 and 1 year

  10. Disease Relapse or Progression

    The number of subjects who experience relapse. Relapse is defined by either morphological, cytogenetic or radiologic evidence of the pretransplant hematologic malignancy.

    Time frame: Day +100 and 1 year

  11. The Number of Subjects With Progression-free Survival.

    This will be measured in months. The event for this endpoint is relapse/progression or death. Patients who are alive and disease-free will be censored at last follow-up.

    Time frame: Day +100 and 1 year

  12. The Number of Subjects With Overall Survival.

    The time in months from the date of transplant to date of death from any cause or for surviving patients, to last follow-up. Patients who are alive and disease-free will be censored at last follow-up.

    Time frame: Day +100 and 1 year

  13. Incidence of Infections

    Number of subjects experiencing a grade ≥3 (CTCAE v5) viral, fungal and/or bacterial infections.

    Time frame: Day +28, Day +100 and 1 year

07

Results

Posted Jul 4, 2025

Participant flow

Participant flow — Overall Study
MilestoneTildrakizumab
Started51
Completed50
Not completed1
Withdrew: Only 50 pts are evaluable as 1 pt withdrew before treatment.1

Outcome measures

PrimaryGVHD-free Relapse-Free Survival

Number of subjects experiencing any of grade III-IV acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death at 12 months

Time frame:
1 year
Reported as:
Number · percentage of subjects
GVHD-free Relapse-Free Survival
percentage of subjectsTildrakizumab
GVHD-free Relapse-Free Survival19.3 (11.8 to 31.4)
SecondaryIncidence of Chronic GVHD

Number of subjects experiencing chronic GVHD defined by NIH Consensus criteria.

Time frame:
Day +180
Reported as:
Number · percentage of subjects
Incidence of Chronic GVHD
percentage of subjectsTildrakizumab
Incidence of Chronic GVHD18 (10 to 32.5)
SecondaryIncidence of Chronic GVHD

Number of subjects experiencing chronic GVHD defined by NIH Consensus criteria.

Time frame:
Day +365
Reported as:
Number · percentage of subjects
Incidence of Chronic GVHD
percentage of subjectsTildrakizumab
Incidence of Chronic GVHD53.7 (40.4 to 68.9)
SecondaryIncidence of Acute GVHD

Number of subjects experiencing grades II-IV and III-IV acute GVHD will be determined at Day +100 and Day +180 post-HCT. Acute GVHD will be graded according to NIH Consensus criteria.

Time frame:
Day +100 and Day +180
Reported as:
Number · percentage of subjects
Incidence of Acute GVHD
percentage of subjectsTildrakizumab
Grade II-IV; Day +10014 (7 to 27.8)
Grade II-IV; Day +18018 (10 to 32.5)
Grade III-IV; Day +1004 (1 to 15.6)
Grade III-IV; Day +1804 (1 to 15.6)
SecondaryIncidence of Acute GI GVHD

Number of subjects experiencing grades II-IV and III-IV acute GI GVHD will be determined at Day +100 and Day +180 post-HCT. This will be graded according to NIH Consensus criteria.

Time frame:
Day +100 and Day +180
Reported as:
Number · percentage of subjects
Incidence of Acute GI GVHD
percentage of subjectsTildrakizumab
Grade II-IV; Day +1006 (2 to 18.1)
Grade II-IV; Day +18010.3 (4.5 to 23.7)
Grade III-IV; Day +1004 (1 to 15.6)
Grade III-IV; Day +1804 (1 to 15.6)
SecondaryPrimary Graft Failure.

Number of subjects experiencing no neutrophil recovery to \> 500 cells/μL by Day 28 post-HCT.

Time frame:
Day 28
Reported as:
Count of participants · Participants
Primary Graft Failure.
ParticipantsTildrakizumab
Primary Graft Failure.0
SecondarySecondary Graft Failure

Number of subjects experiencing initial neutrophil engraftment followed by subsequent decline in absolute neutrophil counts \<500 cells/μL, unresponsive to growth factor therapy, but cannot be explained by disease relapse or drugs.

Time frame:
Up to Day 365
Reported as:
Count of participants · Participants
Secondary Graft Failure
ParticipantsTildrakizumab
Secondary Graft Failure0
SecondaryHematopoietic Recovery According to Neutrophil Count Recovery

This measure is the number of subjects with the event. The number of days to hematopoietic recovery will be assessed according to neutrophil count recovery after hematopoietic stem cell transplant (HSCT). Neutrophil recovery or engraftment is defined as achieving an absolute neutrophil count (ANC) ≥500/mm\^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil engraftment.

Time frame:
Day +28
Reported as:
Count of participants · Participants
Hematopoietic Recovery According to Neutrophil Count Recovery
ParticipantsTildrakizumab
Hematopoietic Recovery According to Neutrophil Count Recovery50
SecondaryHematopoietic Recovery According to Platelet Count Recovery

This measure is the number of subjects with the event. The number of days to hematopoietic recovery will be assessed according to platelet count recovery after HSCT. Platelet recovery is defined by either the first day of a sustained platelet count \>20,000/mm\^3 for three days with no platelet transfusion in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment.

Time frame:
Day +28
Reported as:
Count of participants · Participants
Hematopoietic Recovery According to Platelet Count Recovery
ParticipantsTildrakizumab
Hematopoietic Recovery According to Platelet Count Recovery47
SecondaryNon-relapsed Mortality.

Number of subjects who die after alloHCT without experiencing a relapse.

Time frame:
Day +100 and 1 year
Reported as:
Number · percentage of subjects
Non-relapsed Mortality.
percentage of subjectsTildrakizumab
Day +1002 (.3 to 13.9)
1 year8 (3.1 to 20.5)
SecondaryDisease Relapse or Progression

The number of subjects who experience relapse. Relapse is defined by either morphological, cytogenetic or radiologic evidence of the pretransplant hematologic malignancy.

Time frame:
Day +100 and 1 year
Reported as:
Number · percentage of subjects
Disease Relapse or Progression
percentage of subjectsTildrakizumab
Day +10014 (7 to 27.8)
1 year14 (7 to 27.8)
SecondaryThe Number of Subjects With Progression-free Survival.

This will be measured in months. The event for this endpoint is relapse/progression or death. Patients who are alive and disease-free will be censored at last follow-up.

Time frame:
Day +100 and 1 year
Reported as:
Number · percentage of subjects
The Number of Subjects With Progression-free Survival.
percentage of subjectsTildrakizumab
Day +10084 (74.4 to 94.8)
1 year78 (67.3 to 90.4)
SecondaryThe Number of Subjects With Overall Survival.

The time in months from the date of transplant to date of death from any cause or for surviving patients, to last follow-up. Patients who are alive and disease-free will be censored at last follow-up.

Time frame:
Day +100 and 1 year
Reported as:
Number · percentage of subjects
The Number of Subjects With Overall Survival.
percentage of subjectsTildrakizumab
Day +10098 (94.2 to 100)
1 year80 (69.7 to 91.9)
SecondaryIncidence of Infections

Number of subjects experiencing a grade ≥3 (CTCAE v5) viral, fungal and/or bacterial infections.

Time frame:
Day +28, Day +100 and 1 year
Reported as:
Number · percentage of subjects
Incidence of Infections
percentage of subjectsTildrakizumab
Day +2814 (7 to 27.8)
Day +10016 (8.5 to 30.2)
1 Year20.3 (11.6 to 35.3)

Adverse events

Collected over 12 months following alloHCT (up to 13 months). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tildrakizumab10/50 (20%)11/50 (22%)50/50 (100%)
Most frequent serious events
Showing 10 of 28
Most frequent serious events
EventTildrakizumab
DiarrheaGastrointestinal disorders5/50
Aspartate aminotransferase increasedInvestigations3/50
NauseaGastrointestinal disorders3/50
VomitingGastrointestinal disorders3/50
Alanine aminotransferase increasedInvestigations3/50
AnemiaBlood and lymphatic system disorders2/50
Acute kidney injuryRenal and urinary disorders2/50
HypoxiaRespiratory, thoracic and mediastinal disorders2/50
Respiratory FailureRespiratory, thoracic and mediastinal disorders2/50
Lung InfectionInfections and infestations2/50
Most frequent other events
Showing 10 of 121
Most frequent other events
EventTildrakizumab
Platelet count decreasedInvestigations42/50
White blood cell decreasedInvestigations40/50
Neutrophil count decreasedInvestigations39/50
AnemiaBlood and lymphatic system disorders30/50
Febrile neutropeniaBlood and lymphatic system disorders28/50
Mucositis oralGastrointestinal disorders26/50
AnorexiaMetabolism and nutrition disorders21/50
FatigueGeneral disorders18/50
Sore throatRespiratory, thoracic and mediastinal disorders17/50
DiarrheaGastrointestinal disorders13/50

Baseline characteristics

Fifty-one subjects enrolled. One subject withdrew before treatment. Technically, this patient should be included in the demographics table, because they were enrolled. However, since they received no study drug for non-study-related reasons, they are not part of either the safety population or the efficacy population.

Age, Categorical
Age, Categorical(Participants)Tildrakizumab
<=18 years0
Between 18 and 65 years51
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)Tildrakizumab
Female23
Male28
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Tildrakizumab
American Indian or Alaska Native1
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American1
White47
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Tildrakizumab
United States51
08

Study locations

1 site
  • Froedtert Hospital and the Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
09

References and documents

Publications

  • Runaas L, Fank S, Palen K, Szabo A, Rein LE, Ying G, Salzman N, Samanas L, Abedin S, Chhabra S, Hamadani M, Longo W, Shah NN, Haber J, Gradissimo A, Waters N, Peled JU, Johnson B, Kearl T, Drobyski WR. Tildrakizumab for the prophylaxis of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2026 Apr 28;10(8):2698-2710. doi: 10.1182/bloodadvances.2025019065. PubMed 41632629 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 31, 2022
  • Informed consent form · Dec 13, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 21, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04112810
Lead sponsor
Medical College of Wisconsin
Responsible party
William R. Drobyski, MD (Professor, Medical College of Wisconsin) — Principal investigator
First posted
Oct 2, 2019
Start date
Mar 1, 2020
Primary completion
Jun 1, 2024
Completion
Jun 17, 2024
Results posted
Jul 4, 2025
Last update
Oct 21, 2025

Study contacts

William Drobyski, MD
principal investigator · Medical College of Wisconsin

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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