A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

JRCT ID: jRCT2031240468

Registered date:06/11/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Chronic Graft-versus-host-disease
• Date of first enrollment: 16/11/2024
• Target sample size: 240
• Countries of recruitment: To be determined,Japan
• Study type: Interventional

Intervention(s)

Experimental: Axatilimab + Corticosteroids
Axatilimab and Corticosteroids at the protocol-defined dose.

Experimental: Placebo + Corticosteroids
Matching placebo and Corticosteroids at the protocol-defined dose.

Outcome(s)

Primary Outcome

Event Free Survival (EFS)
Defined from the date of randomization to the date of any predefined event, whichever occurs first.
[Time Frame: Up to 3 years]

Secondary Outcome

1. Objective Response (OR)
[Time Frame: 6 months]
2. Event Free Survival 2
[Time Frame: Up to 3 years]
3. Proportion of participants with a >= 7-point improvement in mLSS total score
[Time Frame: Up to 3 years]
4. Overall Response
[Time Frame: 12 Months]
5. DOR (in responders only)
[Time Frame: Up to 3 years]
6. Best Overall Response (BOR)
[Time Frame: Up to 3 years]
7. Overall Survival (OS)
[Time Frame: Up to 3 years]
8. Nonrelapse mortality (NRM)
[Time Frame: Up to 3 years]
9. Failure-free survival (FFS)
[Time Frame: Up to 3 years]
10. Relapse of hematologic diseases
[Time Frame: Up to 3 years]
11. Time to primary hematologic disease relapse
[Time Frame: Up to 3 years]
12. Percent reduction in daily corticosteroid dose
[Time Frame: 6 months]
13. Proportion of participants who tapered off all corticosteroids
[Time Frame: 6 months]
14. Number of participants with Treatment-emergent Adverse Events (TEAEs)
[Time Frame: Up to 3 years and 30 days]
15. Change from baseline in circulating monocyte number and phenotype (CD14/16)
[Time Frame: Up to 3 years and 30 days]
16. Change from baseline in soluble markers for bone resorption and formation, including bone-specific alkaline phosphatase (BAP) and C-terminal telopeptide (CTX)
[Time Frame: Up to 3 years and 30 days]

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. >= 12 years of age at the time of informed consent.
2. New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy.
3. 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.
4. Adequate hematologic function with ANC >= 0.5 x 109/L independent of growth factors for at least 7 days prior to study entry.
5. Willingness to avoid pregnancy or fathering children.

Exclude criteria

1. Received more than 1 prior allo-HCT. Prior autologous HCT is allowed.
2. Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
3. Received more than 7 days of systemic corticosteroid treatment for cGVHD or unable to begin a prednisone dose >= 1.0 mg/kg per day (or methylprednisolone equivalent) for cGVHD.
4. Received previous systemic treatment for cGVHD, including extracorporeal photopheresis.
5. Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
6. Prior treatment with CSF-1R targeted therapies.
7. Active, uncontrolled bacterial, fungal, parasitic, or viral infection.
8. 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.
9. History of acute or chronic pancreatitis.
10 Active symptomatic myositis.
11. History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease.
12. Severe renal impairment, that is, estimated CrCl < 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or endstage renal disease on dialysis.
13. Impaired liver function, defined as total bilirubin > 1.5 x ULN and/or ALT and AST > 3 x ULN in participants with no evidence of liver cGVHD.
14. Pregnant or breastfeeding.
Other protocol-defined Inclusion/Exclusion Criteria may apply.

Related Information

• Primary Sponsor: Ono Shintaro
• Secondary ID(s): NCT06585774