A Phase 2, Randomized, Open-Label Study Of Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy (AGAVE-256)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

17 Feb 2026 → ongoing

Decision date (initial)

2025-10-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Incyte Corporation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To assess the efficacy of axatilimab monotherapy
versus BAT in cGVHD.

Secondary objectives 5

1. To evaluate the population PK of axatilimab in pediatric participants with cGVHD.
2. To evaluate the benefit of axatilimab monotherapy versus BAT in cGVHD with respect to secondary efficacy endpoints.
3. To evaluate the effect of axatilimab monotherapy versus BAT on overall corticosteroid use in cGVHD.
4. To assess changes in health-related quality of life with axatilimab versus BAT in cGVHD.
5. To evaluate the safety and tolerability of axatilimab monotherapy versus BAT in cGVHD.

Conditions and MedDRA coding

Chronic Graft-Versus-Host Disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003385-PIP01-22

Plan to share IPD

Yes

IPD plan description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Aged ≥ 2 to < 18 years at the time of signing the informed consent.
2. 2. 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.
3. 3. Active, moderate to severe cGVHD requiring systemic immune suppression.
4. 4. 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).
5. 5. Participants with refractory or recurrent active cGVHD who have received at least 2 lines of systemic therapy for cGVHD, including corticosteroids and ruxolitinib.
6. 6. Participants may have overlap cGVHD
7. 7. Karnofsky Performance Scale of ≥ 60 (if aged ≥ 16 years); Lansky Performance Score of ≥ 60 (if aged < 16 years).
8. 8. Adequate hematologic function, defined as ANC ≥ 0.5 × 109/L and platelet count ≥ 20 × 109/L (with or without transfusion).
9. 9. 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.
10. 10. 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.
11. 11. Willingness to avoid pregnancy or fathering children

Exclusion criteria 22

1. 1. Received more than 1 prior allo-HCT. Prior autologous HCT is allowed.
2. 2. Has aGVHD without manifestations of cGVHD.
3. 3. Evidence of relapse of hematologic disease or treatment for relapse after the allo-SCT was performed, including DLI for the treatment of molecular relapse.
4. 4. 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.
5. 5. 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.
6. 6. 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.
7. 7. History of acute or chronic pancreatitis.
8. 8. Active, symptomatic myositis.
9. 9. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
10. 10. Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
11. 11. Previous exposure to CSF-1R–targeted therapies.
12. 12. 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.
13. 13. 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.
14. 14. Active, uncontrolled infection despite appropriate therapy at the time of screening.
15. 15. Active HBV or HCV infection that requires treatment or at risk for HBV reactivation (ie, positive HBsAg).
16. 16. Known HIV seropositive status.
17. 17. Suspected active or latent tuberculosis (as confirmed by a positive tuberculosis blood test).
18. 18. 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.
19. 19. Female adolescent participants who are pregnant or breastfeeding.
20. 20. Participants must not participate in any other interventional study.
21. 21. 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.
22. 22. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. Axatilimab PK parameters, including Cmax, tmax, Cmin, AUC0 t, AUC0-∞, CL, Vz, and t½, as deemed appropriate.
2. • BOR 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.
3. • OR at 12 months, defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD.
4. • DOR (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.
5. • Organ-specific response.
6. Percent reduction in daily corticosteroid dose at C7D1, and participants successfully tapered off all corticosteroids at C7D1.
7. Changes in parameters collected using the pediatric stem cell QoL questionnaire (PedsQL Stem Cell Transplant Module)
8. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 63 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications