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 Least 2 Lines of Systemic Therapy
概览
- 阶段
- 2 期
- 干预措施
- Axatilimab
- 疾病 / 适应症
- Chronic Graft-versus-host-disease
- 发起方
- Syndax Pharmaceuticals
- 入组人数
- 241
- 试验地点
- 201
- 主要终点
- Overall Response Rate (ORR) in the First 6 Cycles as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease (cGVHD)
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy.
详细描述
AGAVE-201 is a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy, safety, and tolerability of axatilimab in participants with recurrent or refractory active cGVHD after failure of at least 2 prior lines of systemic therapy due to progression of disease, intolerability, or toxicity. Participants will be randomized to receive 1 of 3 different axatilimab treatment regimens in 28-day treatment cycles for up to 2 years.
研究者
入排标准
入选标准
- •Participants must be 2 years of age or older, at the time of signing the informed consent.
- •Participants who are allogeneic hematopoietic stem cell transplantation (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.
- •Participants 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.
- •Participants 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.
- •Participants 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.
- •Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged \<16 years)
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Has acute GVHD 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 or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
- •Participants with acquired immune deficiency syndrome (AIDS).
- •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 \[RNA\]).
- •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 (for example, 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).
- •Female participant who is pregnant or breastfeeding.
研究组 & 干预措施
Axatilimab Dose Cohort 3
Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.
干预措施: Axatilimab
Axatilimab Dose Cohort 1
Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years.
干预措施: Axatilimab
Axatilimab Dose Cohort 2
Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.
干预措施: Axatilimab
结局指标
主要结局
Overall Response Rate (ORR) in the First 6 Cycles as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease (cGVHD)
时间窗: First 6 cycles (up to Cycle 7 Day 1; each cycle = 4 weeks)
The ORR was defined as the percentage of participants with objective response (complete response \[CR\] or partial response \[PR\]). CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site.
次要结局
- ORR on Study as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD(Up to 2 years)
- Number of Participants With a Clinically Significant Improvement in Normalized Score on the Modified Lee Symptom Scale(Up to 2 years)
- Duration of Response(Up to 2 years)
- Sustained Response Rate(Up to 2 years)
- Organ-specific Response Rate(Up to 2 years)
- Joints and Fascia Response Rate Based on Refined NIH Response Algorithm for cGVHD(Up to 2 years)
- Percent Reductions in Average Daily Doses (or Equivalent) of Corticosteroid(Up to 2 years)
- Number of Participants Who Discontinue Corticosteroid Use(Up to 2 years)
- Percent Reductions in Average Daily Doses (or Equivalent) of Calcineurin Inhibitors (CNI)(Up to 2 years)
- Number of Participants Who Discontinue CNIs(Up to 2 years)
- Change From Baseline in Circulating Monocyte Number and Phenotype (CD14/16)(Baseline, up to 2 years)
- Number of Participants With Anti-Drug Antibody(Up to 2 years)
- Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Measurable Concentration (AUC0-t)(Approximately 12 months)
- Number of Participants With Treatment-emergent Adverse Events(Up to 2 years)
- Change From Baseline in Bone Turnover Markers(Baseline, up to 2 years)
- Change From Baseline in Bone Density(Baseline, up to 2 years)
- Change From Baseline in Colony Stimulating Factor 1 (CSF-1) and Interleukin 34 (IL-34) Levels(Baseline, up to 2 years)