A Phase 2, Randomized, Open-Label Study of Axatilimab Versus Best Available Therapy in Pediatric Chronic Graft-Versus-Host Disease Post Two Systemic Therapies

Trial ID: 2025-521849-25-00
Protocol: INCA034176-256
Sponsor: Incyte Corp.

Trial statistics

science

test molecule

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

Diseases & Conditions

Chronic graft versus host disease

Objectives

The primary objective is to evaluate the efficacy of axatilimab monotherapy compared to best available therapy in pediatric participants diagnosed with chronic graft-versus-host disease. 5

Secondary objectives include:

Assessment of population pharmacokinetics of axatilimab. 6
Evaluation of secondary efficacy endpoints. 5
Analysis of the impact on total corticosteroid use.
Measurement of changes in health-related quality of life.
Evaluation of safety and tolerability. 4

Participants

This study involves 18 participants diagnosed with chronic Graft-Versus-Host Disease. The study population consists of both male and female pediatric patients aged between 2 and 18 years. Eligible individuals must have a history of allogeneic hematopoietic cell transplantation and present with active, moderate to severe disease requiring systemic immunosuppression. Inclusion requires participants to have refractory or recurrent disease following at least two lines of systemic therapy, including corticosteroids and ruxolitinib. Participants must demonstrate adequate hematologic function, characterized by a specific absolute neutrophil count and platelet count. Performance status is assessed using the Lansky Performance Score for those under 16 years or the Karnofsky Performance Scale for those 16 years and older. The cohort must be willing to undergo best available therapy, such as calcineurin inhibitors, extracellular photoaferesis, or other specified immunosuppressive agents, and must adhere to requirements regarding pregnancy prevention.

Plans and Procedures

This Phase 2, randomized, open-label study is designed to evaluate the efficacy of axatilimab monotherapy compared to best available therapy in pediatric participants diagnosed with chronic graft versus host disease. The research methodology involves assigning participants to receive either an intravenous infusion of axatilimab at a dose of 0.3 mg/kg or one of several established systemic therapies, including cyclosporine, tacrolimus, extracorporal photopheresis, mycophenolate mofetil, mTOR inhibitors, rituximab, imatinib, methotrexate, or ibrutinib. The study includes a screening process to confirm eligibility based on age, history of allogeneic hematopoietic cell transplantation, and disease severity after at least two prior lines of systemic therapy. The primary endpoint is the overall response, defined as complete response or partial response at 6 months in the absence of new systemic therapy. Secondary objectives include the assessment of pharmacokinetics, duration of response, organ-specific response, and changes in quality of life. Study involvement includes regular monitoring for safety, tolerability, and clinical assessments. Participant involvement is subject to the monitoring of adverse events and clinical progression.

Treatment

The experimental treatment consists of axatilimab (INCA034176) administered as a solution for infusion. The dosage is 0.3 mg/kg, which is delivered via intravenous administration.

The comparator arm involves best available therapy, representing the current standard of care for pediatric participants with chronic graft versus host disease.

Efficacy

The primary efficacy endpoint is the overall response rate at 6 months, which is defined as achieving either a complete response or a partial response at the 6-month timepoint (C7D1) without the requirement of new systemic therapy for chronic graft-versus-host disease.

Secondary efficacy assessments include:

Best overall response, defined as the highest level of response achieved within the first 6 months or at any point prior to the initiation of new systemic treatment.
The overall response rate at 12 months.
Duration of response in responders, measured from the date of initial response to the occurrence of disease progression, initiation of new systemic therapy, or death.
Organ-specific response.
The percentage reduction in daily corticosteroid dosage and the proportion of participants successfully tapered off all corticosteroids at C7D1.
Changes in quality of life parameters as measured by the PedsQL Stem Cell Transplant Module.

Additionally, pharmacokinetic parameters, including Cmax, tmax, Cmin, AUC, clearance, volume of distribution, and half-life, will be evaluated.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Aged ≥ 2 to < 18 years at the time of signing the informed consent.
Ability to comprehend and willingness to sign a written ICF for the study. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable, pediatric participants should sign their own assent form.
Active, moderate to severe cGVHD requiring systemic immune suppression.
History of allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood).
Participants with refractory or recurrent active cGVHD who have received at least 2 lines of systemic therapy for cGVHD, including corticosteroids and ruxolitinib.
Participants may have overlap cGVHD
Karnofsky Performance Scale of ≥ 60 (if aged ≥ 16 years); Lansky Performance Score of ≥ 60 (if aged < 16 years).
Adequate hematologic function, defined as ANC ≥ 0.5 × 109/L and platelet count ≥ 20 × 109/L (with or without transfusion).
Concomitant use of systemic corticosteroids is allowed, but not required. Participants on systemic corticosteroids must be on a stable dose of corticosteroids for at least 2 weeks prior to C1D1. Topical and inhaled corticosteroid agents are allowed.
Participants must accept to be treated with one of the following BAT options on C1D1: CNI (cyclosporine or tacrolimus), ECP, MMF, an mTOR inhibitor (everolimus or sirolimus), rituximab, imatinib, methotrexate, or ibrutinib.
Willingness to avoid pregnancy or fathering children

cancel

Exclusion Criteria

Received more than 1 prior allo-HCT. Prior autologous HCT is allowed.
Has aGVHD without manifestations of cGVHD.
Evidence of relapse of hematologic disease or treatment for relapse after the allo-SCT was performed, including DLI for the treatment of molecular relapse.
Maintenance therapy for the primary hematologic disease started within 4 weeks before initiation of study treatment (Day 1) or plans to start maintenance therapy after Day 1.
Severe renal impairment, that is, GFR < 30 mL/min/1.73 m2 as estimated using modified Schwartz formula, or end-stage renal disease on dialysis.
Impaired liver function, defined as total bilirubin > 1.5 × ULN and/or ALT and AST > 3 × ULN in participants with no evidence of liver cGVHD.
History of acute or chronic pancreatitis.
Active, symptomatic myositis.
Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
Previous exposure to CSF-1R–targeted therapies.
For approved or commonly used treatments for cGVHD (other than corticosteroids, CNI and mTOR inhibitor) a washout of 2 weeks or 5 half-lives, whichever is longer, is required at study enrollment.
Treatment with an investigational agent (for any indication) within 30 days of randomization, or within 5 half-lives of the investigational product, whichever is longer.
Active, uncontrolled infection despite appropriate therapy at the time of screening.
Active HBV or HCV infection that requires treatment or at risk for HBV reactivation (ie, positive HBsAg).
Known HIV seropositive status.
Suspected active or latent tuberculosis (as confirmed by a positive tuberculosis blood test).
Administration of live-attenuated vaccines within 4 weeks prior to the first dose of study treatment or anticipated need for live-attenuated vaccines while on study treatment.
Female adolescent participants who are pregnant or breastfeeding.
Participants must not participate in any other interventional study.
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.