Effects of Axatilimab on Skin in Chronic Graft-versus-Host Disease

Mapping On-Target Effects of Axatilimab in Human Chronic Graft-versus-Host Disease Skin: A Prospective Observational Mechanistic Study

Chronic graft-versus-host disease (cGVHD) is a condition that can develop after a stem cell transplant. It occurs when donor immune cells attack the body's tissues. In many people, cGVHD affects the skin, causing inflammation, thickening, and scarring that can limit movement and reduce quality of life.

Axatilimab is a medicine approved by the U.S. Food and Drug Administration (FDA) to treat adults with cGVHD after at least two previous treatments have not worked well enough. Although axatilimab can improve cGVHD, researchers do not fully understand how it changes immune cells in the skin.

The purpose of this study is to learn how axatilimab affects immune cells in the skin and blood of people with cGVHD. Researchers will study skin and blood samples collected before and after participants start axatilimab. The goal is to better understand how the medicine reduces inflammation and scarring and to identify biological changes that occur during treatment.

This is an observational research study. The study does not decide whether participants receive axatilimab, when treatment starts, or what dose they receive. All treatment decisions are made by the participant's treating physician as part of routine medical care.

About 15 adults with cGVHD involving the skin will participate. Ten participants who are starting axatilimab as part of their usual care will have three study visits: before treatment begins, about 2 weeks after starting treatment, and about 12 weeks after starting treatment. At each visit, participants will provide a small skin biopsy and a blood sample. Five participants with cGVHD who are not receiving axatilimab will serve as a comparison group and will complete one study visit with one skin biopsy and one blood sample. Researchers will also review participants' medical records and collect information about their skin disease over time.

Information from this study may help researchers better understand how axatilimab works in people with cGVHD. The findings may also help improve future research and guide the development of treatments for cGVHD and other diseases that cause tissue scarring.

Study Overview

• Status: Not yet recruiting
• Conditions: GVHD; Chronic Graft vs. Host Disease; cGVHD; Graft Versus Host Disease in Skin
• Intervention / Treatment: Drug: Axatilimab

Detailed Description

Chronic graft-versus-host disease (cGVHD) is a common long-term complication of allogeneic stem cell transplantation. It develops when donor immune cells attack the recipient's healthy tissues. The skin is one of the organs most commonly affected. Skin cGVHD can cause inflammation, thickening, hardening, and scarring (fibrosis), which may lead to pain, reduced flexibility, impaired mobility, and decreased quality of life.

Axatilimab is a monoclonal antibody that blocks colony-stimulating factor-1 receptor (CSF1R), a protein found on monocytes and macrophages, which are immune cells involved in inflammation and tissue repair. Axatilimab is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with recurrent or refractory cGVHD after at least two prior lines of systemic therapy. Although clinical trials have shown that axatilimab improves symptoms in many patients, the biological mechanisms by which it reduces inflammation and fibrosis in human tissues are not fully understood.

The purpose of this prospective observational study is to better understand how axatilimab changes immune cells in the skin and blood of people with cGVHD. The study focuses on macrophages because growing evidence suggests that these cells play an important role in promoting tissue fibrosis. Researchers will investigate how macrophages change after treatment with axatilimab and how these changes affect interactions with other cell types, including fibroblasts, which produce connective tissue, and T cells, which regulate immune responses. Understanding these cellular changes may help explain how axatilimab works and identify biological markers associated with treatment response.

This is an observational, non-interventional study. The study does not assign treatment, change a participant's medical care, or determine whether axatilimab is prescribed. Participants who receive axatilimab will do so because their treating physician has independently decided that treatment is appropriate as part of routine clinical care. Researchers will observe biological changes associated with treatment without influencing clinical decisions.

Approximately 15 adults with skin involvement from cGVHD will participate. Ten participants who are planning to start axatilimab as part of their routine care will undergo study evaluations before treatment begins, approximately 2 weeks after starting treatment, and approximately 12 weeks after starting treatment. Five participants with skin cGVHD who are not starting axatilimab will serve as an observational comparison group and will complete one study visit.

Study procedures include collection of small skin punch biopsies and blood samples, review of medical records, and assessment of skin disease. The skin and blood samples will be analyzed using laboratory methods that can examine individual cells and determine where different cell types are located within the skin. These analyses will allow researchers to evaluate changes in immune cell populations, gene activity, and tissue organization before and after treatment. Researchers will also compare these biological changes with clinical measures of skin disease to determine whether early changes in tissue are associated with later clinical improvement.

The primary goal of this study is to characterize the early biological effects of axatilimab on macrophages in the skin. Secondary objectives include evaluating changes in fibroblasts, immune cell organization, and blood biomarkers, and determining whether these biological changes are associated with improvements in skin disease. The study will also compare tissue findings from cGVHD with existing data from systemic sclerosis, another disease characterized by skin fibrosis, to determine whether similar biological pathways are involved.

This study is designed to improve scientific understanding of how axatilimab works in human tissues rather than to evaluate its clinical effectiveness or safety. The knowledge gained may support the development of biomarkers that predict treatment response, improve understanding of cGVHD biology, and guide future research into treatments for cGVHD and other fibrotic diseases.

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Mary Carns, MS; Phone Number: +1-312-503-0406; Email: m-carns@northwestern.edu
• Study Contact Backup: Name: Phillip Cooper; Phone Number: +1-312-503-0406; Email: p-cooper@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adults with chronic graft-versus-host disease (cGVHD) involving the skin who are receiving care at Northwestern Medicine. The study will enroll participants who are initiating axatilimab as part of routine clinical care and an observational comparison cohort of participants with skin cGVHD who are not initiating axatilimab.

Description

Inclusion Criteria:

• Age 18 years or older.
• Diagnosis of chronic graft-versus-host disease (cGVHD) with skin involvement.
• Planned initiation of axatilimab as part of routine clinical care (axatilimab arm) or not planning initiation of axatilimab as part of routine clinical care (control arm).
• Able to undergo a skin biopsy at the time of enrollment.
• Able to provide informed consent.

Exclusion Criteria:

• Unable to provide informed consent.
• Contraindication to skin biopsy, including severe thrombocytopenia or other conditions that make skin biopsy unsafe in the judgment of the investigator.
• Active uncontrolled infection.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Axatilimab arm; Participants with chronic graft-versus-host disease (cGVHD) involving the skin who are initiating axatilimab as part of routine clinical care. This is an observational study; axatilimab is prescribed by the treating physician independent of study participation and is not administered by the study protocol. Participants will undergo study evaluations before starting treatment and approximately 2 and 12 weeks after treatment initiation. Study procedures include skin biopsies, blood collection, review of medical records, and clinical assessment of skin disease to evaluate biological changes associated with axatilimab treatment.	Drug: Axatilimab; Axatilimab is an FDA-approved monoclonal antibody that blocks colony-stimulating factor-1 receptor (CSF1R). In this observational study, axatilimab is prescribed and administered as part of routine clinical care by the treating physician. The study does not assign or administer treatment; it evaluates biological changes associated with axatilimab therapy using skin biopsies, blood samples, and clinical assessments.
Control arm; Participants with mild or controlled chronic graft-versus-host disease (cGVHD) involving the skin who are not initiating axatilimab and are receiving standard clinical management without CSF1R-targeted therapy. This observational comparison group will complete one study visit that includes a skin biopsy, blood collection, review of medical records, and clinical assessment of skin disease. Data and biospecimens from this group will provide a reference for comparison with participants receiving axatilimab to help distinguish biological changes associated with treatment from those associated with chronic cGVHD itself.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CSF1R+ profibrotic macrophages in skin	Within-participant change in the abundance and activation state of CSF1R-positive profibrotic macrophages in skin biopsy specimens after initiation of axatilimab.	Baseline, Week 2, and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fibroblast activation in skin	Within-participant change in the abundance and activation state of fibroblast subsets in skin biopsy specimens after initiation of axatilimab.	Baseline, Week 2, and Week 12
Change in immune cell organization in skin	Within-participant change in the spatial organization and interactions of macrophages, fibroblasts, and T cells within skin biopsy specimens after initiation of axatilimab.	Baseline, Week 2, and Week 12
Change in circulating biomarkers	Within-participant change in blood biomarkers associated with CSF1R pathway activity and immune responses, including CSF1, IL-34, CXCL9, and CXCL10.	Baseline, Week 2, and Week 12
Change in NIH Skin Score	Change in National Institutes of Health (NIH) Skin Score from baseline following initiation of axatilimab.	Baseline and Week 12
Change in Modified Lee Symptom Scale	Change in Modified Lee Symptom Scale score from baseline following initiation of axatilimab.	Baseline and Week 12
Change in corticosteroid dose	Change in systemic corticosteroid dose after initiation of axatilimab.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Alexander Misharin, MD, PhD, Northwestern University; Principal Investigator: Kehinde Adekola, MD, Northwestern University

Publications and helpful links

General Publications

• Wolff D, Cutler C, Lee SJ, Pusic I, Bittencourt H, White J, Hamadani M, Arai S, Salhotra A, Perez-Simon JA, Alousi A, Choe H, Kwon M, Bermudez A, Kim I, Socie G, Chhabra S, Radojcic V, O'Toole T, Tian C, Ordentlich P, DeFilipp Z, Kitko CL; AGAVE-201 Investigators. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024 Sep 19;391(11):1002-1014. doi: 10.1056/NEJMoa2401537.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 22, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: GVHD; cGVHD; axatiliamab
• Additional Relevant MeSH Terms: axatilimab
• Other Study ID Numbers: STU00226060; I-34176-26-13 (Other Grant/Funding Number: Incyte Corporation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) collected for this study will not be made publicly available because of the small sample size and the detailed clinical and molecular data generated, which could increase the risk of participant re-identification despite removal of direct identifiers. Summary results, including aggregate analyses and study findings, will be reported through scientific publications, presentations, and ClinicalTrials.gov, as appropriate.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No