Recurrent/Refractory Active Chronic Graft Versus Host Disease MedDRA version: 20.1 Level: PT Classification code 10066261 Term: Chronic graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: Axatilimab
Product Code: SNDX-6352
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Axatilimab
CAS Number: 2155851-88-8
Current Sponsor code: SNDX-6352
Concentration unit:
Sponsors
Syndax Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be 2 years of age or older, at the time of signing the informed consent. 2. Patients who are allogeneic HSCT recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD (Jagasia 2015). 3. Patients with refractory or recurrent active cGVHD after at least 2 lines of systemic therapy. - Refractory disease 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 investigation therapy for cGVHD. - Patients who have not achieved a response within 3 months on their prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required. - Recurrent cGVHD is active, symptomatic disease (after an initial response to prior therapy) as defined, based on the NIH 2014 consensus criteria, by organ-specific or global assessment or for which the physician believes that a new line of systemic therapy is required. 4. Patients may have persistent active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD. 5. Karnofsky Performance Scale of =60 (if aged 16 years or older); Lansky Performance Score of =60 (if aged =65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: 1. Has acute GVHD 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 patient, in the opinion of the Investigator, unsuitable for the study. 6. Patients with acquired immune deficiency syndrome (AIDS). 7. Hepatitis B (defined as hepatitis B virus [HBV] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid [DNA], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C [HCV] antibody with positive HCV ribonucleic acid [RNA]). 8. Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of randomization, unless previously treated with curative intent and approved by Sponsor’s Medical Monitor (eg, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection). 9. Female patient who is pregnant or breastfeeding. 10. Previous exposure to CSF1-R targeted therapies. 11. Taking agents other than a corticosteroid or either a CNI or mTOR inhibitor is prohibited. See inclusion criteria 9 for guidelines regarding the appropriate use of corticosteroids, CNI, and mTOR inhibitor in combination with study treatment. 12. For approved or commonly used agents, other than corticosteroids, CNI and mTOR inhibitor, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment. 13. Receiving another investigational treatment within 28 days of randomization 14. Patients should not be participating in any other interventional study. Pediatric patients are encouraged to also participate in the ongoing development studies of the Pediatric cGVHD Symptom Scale (PCSS).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the overall response rate (ORR) of axatilimab at 0.3 mg/kg Q2W, 1 mg/kg Q2W, and 3 mg/kg Q4W in patients with cGVHD;Secondary Objective: Efficacy: 1. To evaluate secondary measures of clinical benefit. Safety: 1. To evaluate the safety and tolerability of axatilimab in patients with cGVHD 2. Bone morphology PK/PD: 1. To assess the plasma population PK (pop PK) profile of axatilimab in patients with cGVHD 2. To assess pharmacodynamic profile of axatilimab 3. To determine or assess the changes in monocyte level with response 4. To determine or assess the baseline in monocyte level with response Immunogenicity: 1. Immunogenicity;Primary end point(s): 1. ORR in the first 6 cycles as defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.;Timepoint(s) of evaluation of this end point: 1. During the first 6 cycles, where the first 6 cycles is defined as the time from randomization up to Day 169 or the beginning of Cycle 7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: 1. Proportion of patients with clinically significant improvement in modified Lee Symptom Scale Score (mLSS). 2. ORR on study as defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD. 3. DOR defined as the time from initial response of PR or CR until documented progression of cGVHD, start of new therapy, or death for any reason 4. Sustained response rate (SRR) 5. Organ-specific response rate based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD 6. Joints and fascia response rate based on refined NIH response algorithm for cGVHD 7. Percent reduction in average daily dose (or equivalent) of corticosteroids 8. Proportion of patients who discontinue corticosteroid use after study entry 9. Percent reduction in average daily dose (or equivalent) of calcineurin inhibitors 10. Proportion of patients who discontinue calcineurin inhibitors use after study entry Safety: 1. Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) 2. Change from baseline in values for vital signs, safety laboratory parameters, physical and neurological examination, ECG and Karnofsky/Lansky performance scale 3. Change from baseline in bone turnover markers 4. Change from baseline in bone density Pharmacodynamics (PK) 1. Axatilimab PK parameters and patient factors that may explain variability in drug exposure 2. Change from baseline in colony stimulating factor 1 (CSF-1), interleukin 34 (IL-34) levels and its association with cGVHD response 3. Change from baseline in circulating monocyte number and phenotype (CD14/16) 4. Baseline circulating monocyte number and phenotype (CD14/16) Immunogenicity: 1. Presence of anti-drug antibody (ADA) ;Timepoint(s) of evaluation of this end point: Efficacy: 1-11. Throughout the study Safety: 1-4. Throughout the study Pharmacodynamics: 1-4. Throughout the study Immunogenicity: 1. Day 1 up to Cycle 12, EOT and follow-up visi | — |
Countries
Australia, Belgium, Canada, France, Germany, Greece, Italy, Korea, Republic of, Portugal, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactTimothy O'Toole
Syndax Pharmaceuticals, Inc.
Outcome results
None listed