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

JRCT ID: jRCT2011240011

Registered date:27/04/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Chronic Graft-versus-host-disease
• Date of first enrollment: 30/06/2024
• Target sample size: 20
• Study type: Interventional
• Intervention(s): Axatilimab at the protocol-defined dose.

Outcome(s)

• Primary Outcome: Overall Response Rate in the First 6 Cycles

Secondary Outcome

1. Proportion of participants with a >= 7-point improvement in modified Lee symptom scale (mLSS) score
2. Overall Response Rate
3. Duration of Response
4. Organ-specific Response Rate
5. Percent reduction in average daily dose (or equivalent) of corticosteroids
6. Proportion of participants who discontinue corticosteroid use
7. Number of participants with Treatment-emergent Adverse Events (TEAEs)
8. Change from baseline in Karnofsky/Lansky performance status
9. Axatilimab pharmacokinetic (PK) in Plasma
10. Number of Participants with Anti-Drug Antibody (ADA)

Key inclusion & exclusion criteria

• Age minimum: >= 6age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. At least 6 years of age at the time of signing the ICF.
2. Ability to comprehend and willingness to sign a written ICF for the study.
2-1. 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.
3. 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.
3-1. 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.
3-2. Refractory disease is defined as meeting any of the following criteria:
3-2-1. The development of 1 or more new sites of disease while being treated for cGVHD.
3-2-2. Progression of existing sites of disease despite at least 1 month of standard or investigational therapy for cGVHD.
3-2-3. 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.
3-3. 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.
4. 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.
5. Karnofsky performance score of >= 60 (if aged 16 years or older); Lansky performance score of >= 60 (if aged younger than 16 years).
6. Adequate organ and bone marrow functions evaluated during the 14 days prior to the start of study treatment.
7. Creatinine clearance >= 30 mL/min/1.73 m2 based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
8. 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.
9. Concomitant use of protocol-defined immunosuppressant is allowed but not required.
10. Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.

Exclude criteria

1. Has aGVHD without manifestations of cGVHD.
2. Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
3. History of acute or chronic pancreatitis.
4. History of myositis.
5. 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.
6. Has acquired immunodeficiency syndrome.
7. History of latent or active TB based on protocol-defined criteria.
8. Active HBV or HCV infection that requires treatment, or at risk for HBV reactivation (ie, positive HBsAg).
9. Pregnant or breastfeeding.
10. Previous exposure to CSF-1R targeted therapies.
11. 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.
12. Has received an investigational treatment within 28 days prior to the start of study treatment.
13. Currently participating in any other interventional study.

Related Information

• Primary Sponsor: Ono Shintaro
• Secondary ID(s): NCT06263478