Chronic Graft-versus-host-disease
Conditions
Keywords
cGVHD
Brief summary
This study will be conducted to determine the clinical efficacy of axatilimab in Japanese participants with chronic graft-versus-host disease (cGVHD).
Interventions
DRUGINCA034176
IV infusion
Sponsors
Incyte Biosciences Japan GK
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 6 years of age at the time of signing the ICF. * Ability to comprehend and willingness to sign a written ICF for the study. • For participants 6 to 17 years old, a parent/guardian must provide consent for pediatric participants; when applicable, pediatric participants should also sign an assent form. * Japanese participants who are allo-HSCT recipients with active, refractory, or recurrent cGVHD requiring systemic immune suppression despite at least 2 lines of prior systemic therapy. * Active cGVHD is defined as the presence of signs and symptoms of cGVHD per the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD. * Refractory disease is defined as meeting any of the following criteria: * The development of 1 or more new sites of disease while being treated for cGVHD. * Progression of existing sites of disease despite at least 1 month of standard or investigational therapy for cGVHD. * Participants who did not achieve a response within 3 months on prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required. * Recurrent cGVHD is defined as active, symptomatic disease (after an initial response to prior therapy) based on the NIH 2014 consensus criteria by organ-specific or global assessment or for which the physician believes a new line of systemic therapy is required. * Participants may have persistent, active aGVHD and cGVHD manifestations (overlap syndrome), as defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD. * Karnofsky performance score of ≥ 60 (if aged 16 years or older); Lansky performance score of ≥ 60 (if aged younger than 16 years). * Adequate organ and bone marrow functions evaluated during the 14 days prior to the start of study treatment. * Creatinine clearance ≥ 30 mL/min based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants. * Concomitant use of a systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a participant is taking a corticosteroid, it must be a stable dose for at least 2 weeks prior to the start of study treatment. * Concomitant use of protocol-defined immunosuppressant is allowed but not required. * Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.
Exclusion criteria
* Has aGVHD without manifestations of cGVHD. * Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening. * History of acute or chronic pancreatitis. * History of myositis. * History or other evidence of severe illness, uncontrolled infection, allergy to excipients, or any other conditions that would make the participant, in the opinion of the investigator, unsuitable for the study. * Has acquired immunodeficiency syndrome. * History of latent or active TB based on protocol-defined criteria. * Active HBV or HCV infection that requires treatment, or at risk for HBV reactivation (ie, positive HBsAg). * Pregnant or breastfeeding. * Previous exposure to CSF-1R targeted therapies. * Use of any agent other than corticosteroids, or the immunosuppressant for the treatment of cGVHD within 2 weeks or 5 half-lives, whichever is shorter, prior to the start of study treatment. * Has received an investigational treatment within 28 days prior to the start of study treatment. * Currently participating in any other interventional study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) in the First 6 Treatment Cycles, as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | up to the end of Cycle 6 (up to 168 days) | ORR was defined as the percentage of participants with a physician-assessed complete response (CR) or a physician-assessed partial response (PR), evaluated as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in chronic graft-versus-host disease (cGVHD). A participant was considered an objective responder if they had an overall response of CR or PR at any timepoint up to the beginning of Cycle 7. CR was defined as the resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a ≥7-point Improvement in Modified Lee Symptom Scale (mLSS) Score | before Cycle 7 Day 1 (up to 168 days); during study (up to 12.8 months) | The mLSS is a 28-item instrument comprising 7 subscales, designed to assess the impact of cGVHD on a participant's symptoms. Participants were asked to indicate the degree of "bother" during the past 7 days due to symptoms in 7 domains (skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, emotional distress) potentially affected by cGVHD. A mLSS responder is defined as a participant who achieved at least a 7-point improvement from baseline in the normalized mLSS score. This score is on a 0-100 scale, calculated as the average of the subscale scores. |
| ORR, as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | up to 12.8 months | ORR was defined as the percentage of participants with a physician-assessed CR or a physician-assessed PR, evaluated as defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD. A participant was considered an objective responder if they had an overall response of CR or PR at any post-baseline visit. CR was defined as the resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. |
| Duration of Response (DOR) in Participants With a Response in the First 6 Treatment Cycles | up to 13.8 months (maximum duration of treatment [12.8 months] plus 30 days) | Duration of response was defined as the time from the first response of either CR or PR until progression of cGVHD, start of another anti-GVHD treatment, or death from any cause, whichever was earlier. CR was defined as the resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. DOR was assessed for participants whose first CR or PR occurred during the first 6 treatment cycles. A response was followed until the response ended, regardless of whether the response ended during the first 6 treatment cycles or after Cycle 6. |
| Organ-specific Response Rate | up to 12.8 months | Organ-specific response rate was defined as the percentage of participants with a CR or PR for the 9 individual organs based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD (skin, eyes, mouth, esophagus, upper gastrointestinal (GI) tract, lower GI, liver, lungs, and joints and fascia) in participants with each corresponding organ involvement at baseline. |
| Percent Reduction in Average Daily Dose (or Equivalent) of Corticosteroids in the First 6 Treatment Cycles | up to the end of Cycle 6 (up to 168 days) | Participants may have been taking a corticosteroid upon study entry. At the discretion of the investigator, the corticosteroid dose may have been tapered after the first 4 weeks of study drug administration for participants who achieved either a PR or CR. Percent reduction was calculated as the (\[difference between the baseline value and the post-baseline value\]/divided by the baseline value) x 100. |
| Percentage of Participants Who Discontinued Corticosteroid Use After Study Entry in the First 6 Treatment Cycles | up to the end of Cycle 6 (up to 168 days) | Participants may have been taking a corticosteroid upon study entry. At the discretion of the investigator, the corticosteroid dose may have been tapered after the first 4 weeks of study drug administration for participants who achieved either a PR or CR. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to 13.8 months | An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. For the purposes of analysis, all AEs were considered to be TEAEs unless the AE could unequivocally be defined as not treatment emergent. |
| Number of Participants With Any ≥Grade 3 TEAE | up to 13.8 months | An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. For the purposes of analysis, all AEs were considered to be TEAEs unless the AE could unequivocally be defined as not treatment emergent. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal. |
| Change From Baseline in Karnofsky/Lansky Performance Status | up to 13.8 months | The Karnofsky/Lansky performance status allows participants to be classified as to their functional impairment on a scale from 0 to 100. The lower the score, the worse the survival for most serious illnesses. The score can be used to compare the effectiveness of different therapies and to assess the prognosis in individual participants. The Karnofsky scale is designed for participants aged 16 years and older, and the Lansky scale is designed for participants younger than 16 years. Change from baseline was calculated as the post-baseline value minus the baseline value. |
| Percentage of Participants Positive for Anti-drug Antibodies (ADAs) | up to 12.8 months | Antibodies to axatilimab were evaluated in plasma samples collected from all participants. |
| INCA034176 Concentration | up to 12.8 months | Plasma samples were collected for pharmacokinetic (PK) analysis. |
Countries
Japan
Contacts
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Participant flow
Pre-assignment details
This study was conducted at 14 study centers in Japan. Data collected through a cutoff date of 06 August 2025 have been included in this summary.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 19.64 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 19 / 21 |
| serious Total, serious adverse events | 7 / 21 |
Outcome results
None listed