Clinical trial NCT06263478: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Graft-versus-host-disease
Keywords: cGVHD
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2024-02-16
Enrollment: 21
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate in the First 6 Cycles
timeFrame: Up to Cycle 7 (Day 169)
Secondary outcomes:
measure: Proportion of participants with a ≥ 7-point improvement in modified Lee symptom scale (mLSS) score
timeFrame: Up to 2 years
measure: Overall Response Rate
timeFrame: Up to 2 years
measure: Duration of Response
timeFrame: Up to 2 years
measure: Organ-specific Response Rate
timeFrame: Up to 2 years
measure: Percent reduction in average daily dose (or equivalent) of corticosteroids
timeFrame: Up to 2 years
measure: Proportion of participants who discontinue corticosteroid use
timeFrame: Up to 2 years
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 2 years and 30 days
measure: Change from baseline in Karnofsky/Lansky performance status
timeFrame: Up to 2 years and 30 days
measure: Axatilimab pharmacokinetic (PK) in Plasma
timeFrame: Up to 2 years and 30 days
measure: Number of Participants with Anti-Drug Antibody (ADA)
timeFrame: Up to 2 years and 30 days
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Fukui
country: Japan
facility: University of Fukui Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Hyogo
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kanagawa
country: Japan
facility: Tokai University Hospital
city: Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Nagoya-shi
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka Prefectural Hospital Organization Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Saitama-shi, Saitama,
country: Japan
facility: Saitama Prefectural Children'S Medical Center
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
city: Tokyo
country: Japan
facility: National Center For Child Health and Development
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: