Indianapolis, Indiana 46202

  • disease

Purpose:

AGAVE-201 is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in patients with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy due to progression of disease, intolerability or toxicity.


Study summary:

AGAVE-201 is a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in patients with recurrent or refractory active cGVHD who have received at least 2 prior lines of systemic therapy due to progression of disease, intolerability or toxicity. Disease progression is defined 1) by the NIH 2014 consensus criteria, either in terms of organ specific algorithm or global assessment or 2) as active, symptomatic cGVHD for whom the physician believes that a new line of systemic therapy is required.


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 despite 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 <16 years) 6. Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization. 7. Creatinine clearance (CrCl) ≥30 mL/min/1.73 m2 based on the Cockcroft-Gault formula in adult patients and Schwartz formula in pediatric patients. 8. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 9. Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a patient is taking corticosteroids at study randomization, they must be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1. 10. Concomitant use of CNI or sirolimus is allowed but not required. 11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. A parent/guardian should provide consent for pediatric patients unable to provide consent themselves; in addition, where applicable pediatric patients should sign their own assent form. Exclusion Criteria: Patients are excluded from the study if any of the following criteria apply: 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 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 for treatment of cGVHD other than corticosteroids and either a CNI or sirolimus is prohibited. See Inclusion Criteria 9 for guidelines regarding the appropriate use of corticosteroids, CNI, and sirolimus in combination with study treatment. 12. For approved or commonly used agents, other than corticosteroids, CNI and sirolimus, 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 developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).


Study is Available At:


Original ID:

SNDX-6352-0504


NCT ID:

NCT04710576


Secondary ID:


Study Acronym:

AGAVE-201


Brief Title:

A Study of Axatilimab at 3 Different Doses in Patients With Chronic Graft Versus Host Disease (cGVHD)


Official Title:

AGAVE-201, A Phase 2, Open-label, Randomized, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Axatilimab at 3 Different Doses in Patients With Recurrent or Refractory Active Chronic Graft Versus Host Disease Who Have Received at Lea


Overall Status:

Recruiting


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

2 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Syndax Pharmaceuticals


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

3


Number of Groups:

0


Total Enrollment:

210


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Michael Meyers, M.D., Ph.D.
Study Director
Syndax Pharmaceuticals, Inc.
Primary Contact:Christine Quaranto
781-684-9824
cquaranto@syndax.com
Backup Contact:Sue Fischer
781-795-9419
sfischer@syndax.com

Study Dates

Start Date:March 4, 2021
Completion Date:July 2023
Completion Type:Anticipated
Primary Completion Date:July 2023
Primary Completion Type:Anticipated
Verification Date:May 2021
Last Changed Date:May 4, 2021
First Received Date:January 5, 2021

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Terminal phase volume of distribution
Time Frame:approximately 12 months
Safety Issues:False
Description:Vz will be computed
Outcome Type:Secondary Outcome
Measure:Clearance
Time Frame:approximately 12 months
Safety Issues:False
Description:CL will be computed
Outcome Type:Secondary Outcome
Measure:Terminal phase half-life
Time Frame:approximately 12 months
Safety Issues:False
Description:t1/2 will be computed
Outcome Type:Secondary Outcome
Measure:Terminal disposition phase rate constant
Time Frame:approximately 12 months
Safety Issues:False
Description:terminal disposition phase rate constant will be computed
Outcome Type:Secondary Outcome
Measure:Time to observed maximum plasma concentration
Time Frame:approximately 12 months
Safety Issues:False
Description:Tmax will be computed
Outcome Type:Secondary Outcome
Measure:Observed maximum plasma concentration
Time Frame:approximately 12 months
Safety Issues:False
Description:Cmax will be computed
Outcome Type:Secondary Outcome
Measure:Percentage of estimated part for the calculation of AUC0-inf
Time Frame:approximately 12 months
Safety Issues:False
Description:%AUCextra will be computed
Outcome Type:Secondary Outcome
Measure:Area under the plasma concentration-time curve from time 0 to infinity [Phase 1]
Time Frame:approximately 12 months
Safety Issues:False
Description:AUC0-inf will be computed
Outcome Type:Secondary Outcome
Measure:Area under the plasma concentration-time curve from time 0 to time of last measurable concentration [Phase 1]
Time Frame:approximately 12 months
Safety Issues:False
Description:AUC0-t will be computed
Outcome Type:Secondary Outcome
Measure:Presence of Anti-Drug Antibody
Time Frame:approximately 12 months
Safety Issues:False
Description:To assess the immunogenicity of SNDX-6352
Outcome Type:Secondary Outcome
Measure:To determine or assess the baseline in monocyte level with response
Time Frame:approximately 12 months
Safety Issues:False
Description:Baseline circulating monocyte number and phenotype (CD14/16)
Outcome Type:Secondary Outcome
Measure:To determine or assess the changes in monocyte level with response
Time Frame:approximately 12 months
Safety Issues:False
Description:Change from baseline in circulating monocyte number and phenotype (CD14/16)
Outcome Type:Secondary Outcome
Measure:Calcineurin inhibitor discontinuation
Time Frame:approximately 30 Months
Safety Issues:False
Description:Proportion of patients who discontinue calcineurin inhibitors after study entry.
Outcome Type:Secondary Outcome
Measure:Calcineurin inhibitor reduction
Time Frame:approximately 30 Months
Safety Issues:False
Description:Percent reductions in average daily doses (or equivalent) of calcineurin inhibitors after study entry .
Outcome Type:Secondary Outcome
Measure:Corticosteroid discontinuation
Time Frame:approximately 30 Months
Safety Issues:False
Description:Proportion of patients who discontinue corticosteroid use after study entry.
Outcome Type:Secondary Outcome
Measure:Corticosteroid reduction
Time Frame:approximately 30 Months
Safety Issues:False
Description:Percent reductions in average daily doses (or equivalent) of corticosteroid after study entry.
Outcome Type:Secondary Outcome
Measure:Organ-specific Response Rate
Time Frame:approximately 30 Months
Safety Issues:False
Description:Proportion of patients 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 GI, Lower GI, Liver, Lungs and Joints and Fascia)
Outcome Type:Secondary Outcome
Measure:Sustained Response Rate
Time Frame:at least 20 weeks
Safety Issues:False
Description:Proportion of patients with objective response lasting for at least 20 weeks (140 days) from the time of initial response. Responses by organ system will be assessed based on the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD
Outcome Type:Secondary Outcome
Measure:To evaluate the safety and tolerability of axatilimab in patients with cGVHD
Time Frame:Approximately 30 months; from date of consent to 90 days after last dose of study treatment for AEs
Safety Issues:False
Description:Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by the NCI CTCAE version 5.0
Outcome Type:Secondary Outcome
Measure:To evaluate key secondary measures of clinical benefit for patients with cGVHD
Time Frame:Approximately 6 Months
Safety Issues:False
Description:Proportion of patients with a >5-point improvement in normalized score on the modified Lee Symptom Scale.
Outcome Type:Secondary Outcome
Measure:Duration of Response
Time Frame:Day 1 of each 28-Day cycle for up to 12 cycles
Safety Issues:False
Description:The time from best response of partial response or complete response until documented progression of cGVHD, start of new therapy, or death for any reason.
Outcome Type:Primary Outcome
Measure:Overall response rate in the first 6 cycles
Time Frame:Approximately 6 Months
Safety Issues:False
Description:The proportion of patients with objective response 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

Study Interventions

Intervention Type:Drug
Name:axatilimab
Description:Axatilimab (SNDX-6352) is a high-affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGVHD.
Arm Name:Axatilimab (SNDX-6352) Dose Cohort 1 - 0.3 mg/kg I
Other Name:SNDX-6352

Study Arms

Study Arm Type:Active Comparator
Arm Name:Axatilimab (SNDX-6352) Dose Cohort 3 - 3 mg/kg IV Q4W
Description:IV infusion; Axatilimab (SNDX-6352) 3 mg/kg Q4W
Study Arm Type:Active Comparator
Arm Name:Axatilimab (SNDX-6352) Dose Cohort 2 - 1 mg/kg IV Q2W
Description:IV infusion; Axatilimab (SNDX-6352) 1 mg/kg Q2W
Study Arm Type:Active Comparator
Arm Name:Axatilimab (SNDX-6352) Dose Cohort 1 - 0.3 mg/kg IV Q2W
Description:IV infusion; Axatilimab (SNDX-6352) 0.3 mg/kg Q2W

Study Agencies

Agency Class:Industry
Agency Type:Lead Sponsor
Agency Name:Syndax Pharmaceuticals

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: July 28, 2021

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