AXATILIMAB for Chronic graft-versus-host disease

Inclusion criteria

• {"criterion_text":"- 1.\tAged ≥ 2 to < 18 years at the time of signing the informed consent.\n- 10.\tParticipants 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.\n- 11.\tWillingness to avoid pregnancy or fathering children\n- 2.\tAbility 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.\n- 3.\tActive, moderate to severe cGVHD requiring systemic immune suppression.\n- 4.\tHistory 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).\n- 5.\tParticipants with refractory or recurrent active cGVHD who have received at least 2 lines of systemic therapy for cGVHD, including corticosteroids and ruxolitinib.\n- 6.\tParticipants may have overlap cGVHD\n- 7.\tKarnofsky Performance Scale of ≥ 60 (if aged ≥ 16 years); Lansky Performance Score of ≥ 60 (if aged < 16 years).\n- 8.\tAdequate hematologic function, defined as ANC ≥ 0.5 × 109/L and platelet count ≥ 20 × 109/L (with or without transfusion).\n- 9.\tConcomitant 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."}

Exclusion criteria

• {"criterion_text":"- 1.\tReceived more than 1 prior allo-HCT. Prior autologous HCT is allowed.\n- 10.\tSystemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.\n- 11.\tPrevious exposure to CSF-1R–targeted therapies.\n- 12.\tFor 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.\n- 13.\tTreatment with an investigational agent (for any indication) within 30 days of randomization, or within 5 half-lives of the investigational product, whichever is longer.\n- 14.\tActive, uncontrolled infection despite appropriate therapy at the time of screening.\n- 15.\tActive HBV or HCV infection that requires treatment or at risk for HBV reactivation (ie, positive HBsAg).\n- 16.\tKnown HIV seropositive status.\n- 17.\tSuspected active or latent tuberculosis (as confirmed by a positive tuberculosis blood test).\n- 18.\tAdministration 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.\n- 19.\tFemale adolescent participants who are pregnant or breastfeeding.\n- 2.\tHas aGVHD without manifestations of cGVHD.\n- 20.\tParticipants must not participate in any other interventional study.\n- 21.\tAny 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.\n- 22.\tThe 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.\n- 3.\tEvidence of relapse of hematologic disease or treatment for relapse after the allo-SCT was performed, including DLI for the treatment of molecular relapse.\n- 4.\tMaintenance 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.\n- 5.\tSevere renal impairment, that is, GFR < 30 mL/min/1.73 m2 as estimated using modified Schwartz formula, or end-stage renal disease on dialysis.\n- 6.\tImpaired liver function, defined as total bilirubin > 1.5 × ULN and/or ALT and AST > 3 × ULN in participants with no evidence of liver cGVHD.\n- 7.\tHistory of acute or chronic pancreatitis.\n- 8.\tActive, symptomatic myositis.\n- 9.\tKnown allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds."}

Primary endpoints

• {"endpoint_text":"- OR at 6 months, defined for each treatment group as CR or PR at 6 months (C7D1) in the absence of new systemic therapy for cGVHD.","definition_or_measurement_approach":"Defined for each treatment group as CR or PR at 6 months (C7D1) in the absence of new systemic therapy for cGVHD."}

Secondary endpoints

• {"endpoint_text":"- Axatilimab PK parameters, including Cmax, tmax, Cmin, AUC0 t, AUC0-∞, CL, Vz, and t½, as deemed appropriate.\n- •\tBOR defined as best response of CR or PR in the first 6 months (up to and including C7D1), and at any timepoint up to the initiation of new systemic therapy for cGVHD.\n- •\tOR at 12 months, defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD.\n- •\tDOR (in responders only), defined as the time from the date of first response (PR or CR) to the date of progression of cGVHD, initiation of new systemic treatment for cGVHD, or death from any cause, whichever comes first.\n- •\tOrgan-specific response.\n- Percent reduction in daily corticosteroid dose at C7D1, and participants successfully tapered off all corticosteroids at C7D1.\n- Changes in parameters collected using the pediatric stem cell QoL questionnaire (PedsQL Stem Cell Transplant Module)\n- Safety and tolerability will be assessed by evaluating the frequency and severity of AEs (including SAEs), including changes in clinical assessments, laboratory assessments, Tanner stage, and KPS/LPS scores.","definition_or_measurement_approach":"Definitions provided within the endpoint texts where specified (e.g., PK parameters listed; BOR defined as best response of CR or PR in first 6 months; OR at 12 months defined as CR or PR at 12 months without new systemic therapy; DOR defined as time from first response to progression/initiation of new systemic therapy or death). Other endpoints measured by listed instruments (PedsQL Stem Cell Transplant Module) or clinical/laboratory/Tanner/KPS/LPS assessments."}

Italy

Earliest CTIS Part Ii Submission Date

18-07-2025

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

203

Number Of Sites

6

Number Of Participants

12

Germany

Earliest CTIS Part Ii Submission Date

18-07-2025

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

203

Number Of Sites

8

Number Of Participants

15

Belgium

Earliest CTIS Part Ii Submission Date

01-10-2025

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

142

Number Of Sites

2

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

07-05-2026

Processing Time Days

237

Number Of Sites

5

Number Of Participants

10

Primary sponsor

Full Name

Incyte Corp.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States