A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Axatilimab Monotherapy in Japanese Participants With Recurrent or Refractory Active Chronic Graft-Versus-Host Disease

A Phase 3, Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Axatilimab Monotherapy in Japanese Participants With Recurrent or Refractory Active Chronic Graft-Versus-Host Disease After at Least 2 Lines of Systemic Therapy

This study will be conducted to determine the clinical efficacy of axatilimab in Japanese participants with chronic graft-versus-host disease (cGVHD).

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Graft-versus-host-disease
• Intervention / Treatment: Drug: INCA034176

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Incyte Biosciences Japan G.K. Medical Information Center; Phone Number: 81-120-094-139; Email: jpmedinfo@incyte.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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/1.73 m2 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Axatilimab Dose; Axatilimab at the protocol-defined dose.	Drug: INCA034176; IV infusion; Other Names: Axatilimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate in the First 6 Cycles	The overall response rate will be assessed by the number of participants with objective response by Cycle 7 (28-day cycles), Day 1, with responses defined by the 2014 NIH consensus criteria.	Up to Cycle 7 (Day 169)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a ≥ 7-point improvement in modified Lee symptom scale (mLSS) score		Up to 2 years
Overall Response Rate	Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.	Up to 2 years
Duration of Response	Defined as the time from initial partial response or complete response until documented progression of cGVHD, start of new therapy, or death for any reason.	Up to 2 years
Organ-specific Response Rate	Organ-specific response is defined as the number of participants with objective response for the nine individual organs based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD (skin, eyes, mouth, esophagus, upper gastrointestinal [GI], lower GI, liver, lungs and joints and fascia).	Up to 2 years
Percent reduction in average daily dose (or equivalent) of corticosteroids		Up to 2 years
Proportion of participants who discontinue corticosteroid use		Up to 2 years
Number of participants with Treatment-emergent Adverse Events (TEAEs)	Defined as adverse events reported for the first time or worsening of a pre-existing event from the time the participant signs the informed consent form (ICF) until at least 30 days after the end of trial (EOT) or until start of new cGVHD therapy.	Up to 2 years and 30 days
Change from baseline in Karnofsky/Lansky performance status		Up to 2 years and 30 days
Axatilimab pharmacokinetic (PK) in Plasma	Axatilimab concentration in plasma.	Up to 2 years and 30 days
Number of Participants with Anti-Drug Antibody (ADA)		Up to 2 years and 30 days

Collaborators and Investigators

• Sponsor: Incyte Biosciences Japan GK
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: cGVHD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: INCA34176-358

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes