A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Axatilimab (INCA034176) and Corticosteroids as Initial Treatment for Chronic Graft-Versus Host Disease (AXemplify 357)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

25 Feb 2025 → ongoing

Decision date (initial)

2025-01-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety

To compare the efficacy of axatilimab versus placebo in combination with corticosteroids as initial treatment for moderate or severe cGVHD.

Secondary objectives 1

1. To evaluate the clinical benefit of axatilimab in combination with corticosteroids in participants with cGVHD

Conditions and MedDRA coding

chronic graft-versus-host disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. ≥ 12 years of age at the time of informed consent.
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. New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy (Jagasia et al 2015). a. Moderate cGVHD: At least 1 organ (except lung) with a score of 2, ≥ 3 organs involved with a score of 1 in each organ, or lung score of 1. b. Severe cGVHD: At least 1 organ with a score of 3, or lung score of 2 or 3. Note 1: Diagnosis of cGVHD requires at least 1 diagnostic feature of cGVHD or at least 1 distinctive feature plus additional test such as biopsy, PFTs, Schirmer test, or radiographic imaging showing cGVHD in the same or another organ (see Appendix C). Participants with single-organ, genitourinary involvement or liver involvement as the only manifestation of cGVHD are not eligible. Note 2: Candidates who transition from active aGVHD to cGVHD without tapering off corticosteroids (< 0.25 mg/kg per day methylprednisolone or equivalent) and/or CNIs are eligible.
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). Recipients of myeloablative, nonmyeloablative, or reduced-intensity conditioning are eligible.
5. KPS score ≥ 60% if 16 years of age or older; LPS score ≥ 60% if younger than 16 years of age.
6. Adequate hematologic function with ANC ≥ 0.5 × 109/L independent of growth factors for at least 7 days prior to study entry.
7. Willingness to avoid pregnancy or fathering children.

Exclusion criteria 5

1. Received more than 1 prior allo-HCT. Prior autologous HCT is allowed.
2. Suspected active or latent tuberculosis (as confirmed by a positive QuantiFERON® test).
3. Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-HCT was performed, including DLIs for the treatment of molecular relapse. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
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. Corticosteroid therapy at doses > 0.25 mg/kg per day methylprednisolone or equivalent for any treatment other than the diagnosis of cGVHD within 7 days of randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EFS, defined as the time from the date of randomization to the date of the first EFS event. Events are defined as addition or initiation of new systemic therapy for cGVHD, death due to any cause, or Day 1 in the case of treatment failure (non-CR or non-PR by Month 6).

Secondary endpoints 3

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. Response assessment will be based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD (refined NIH response algorithm for cGVHD disease in joints and fascia [Inamoto et al 2020]).
2. Response, defined as the proportion of participants with a ≥ 7-point improvement in mLSS total score at 6 months (C7D1).
3. EFS2, defined as the time from the date of randomization to the date of the first EFS event. Events are defined as date of progression based on best prior organ status (nadir in score level), addition or initiation of new systemic therapy for cGVHD, death due to any cause, or Day 1 in the case of treatment failure (non-CR or non-PR by Month 6).

Investigational products

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

Test 1

Comparator 2

Placebo 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

Third parties 5

Locations

8 EU/EEA countries · 66 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 94 files

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

Application history

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