An Open-Label, Multicenter, Phase 1/2 Dose-Escalation and Expansion Trial Evaluating the Safety and Efficacy of FT839 in Participants With Autoimmune Diseases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 446
- 试验地点
- 1
- 主要终点
- Phase 1: Incidence of Dose-limiting Toxicity, Adverse Events, and Serious Adverse Events
研究概览
简要总结
The primary objectives of this trial are to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose of FT839 with or without rituximab and/or background therapy and/or conditioning therapy.
详细描述
This is a multicenter, Phase 1/2, open-label trial designed to evaluate the safety, pharmacokinetics (PK), anti-B-cell activity, and clinical activity of FT839 in participants with moderate-to-severe ANCA-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc).
Participants will receive FT839 as monotherapy or in combination with rituximab, with or without conditioning therapy and/or stable background therapy. Participants will be enrolled in 2 stages during the Phase 1 portion of the trial: a dose-escalation stage and a dose-expansion stage. In the dose-escalation stage, safety and tolerability will be assessed to define the MTD (or through the maximum assessed dose [MAD] in the absence of dose-limiting toxicities [DLTs] defining the MTD). The DLT evaluation period will extend from Day 1 through Day 29. Participants will be followed during the post-treatment follow-up period for up to 2 years after the first dose of FT839, followed by long-term-follow-up for safety and survival for up to 15 years after the first dose of FT839.
In the dose-expansion stage, participants will be enrolled into disease-specific cohorts to further evaluate the safety and activity of FT839.
Following completion of the Phase 1 portion, the Phase 2 portion of the trial will further evaluate the efficacy of FT839 within each disease cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 to ≤70 years
- •Must have active B-cell mediated autoimmune disease (AAV, IIM, RA, SLE, or SSc) confirmed by standard criteria
- •Moderate to severe disease, requiring at least two prior treatments that were ineffective
- •Adequate organ function to tolerate treatment
- •Able to provide informed consent and comply with study procedures
排除标准
- •Diagnosis of more than 1 disease under study (AAV, IIM, RA, SSc, or SLE) or overlap syndrome
- •Women must not be pregnant or nursing
- •Severe Organ Dysfunction: Significant heart, lung, liver, or kidney impairment.
- •Active or chronic infections
- •Active or recent malignancies
- •Prior CAR T-cell therapy or organ transplantation
- •Known allergies to study treatments
- •Body weight <45 kg
- •Active central nervous system (CNS) symptoms attributable to autoimmune disease or nonmalignant CNS disease within 12 months prior to trial intervention
- •Receipt of any anti-CD19- or anti-CD20-directed therapy within 6 months prior to trial intervention
研究组 & 干预措施
FT839 monotherapy (Regimen C)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
FT839 + Rituximab (Regimen A)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
FT839 + Rituximab with stable background therapy (Regimen B)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
FT839 with stable background therapy (Regimen D)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
Conditioning + FT839 + Rituximab (Regimen E)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
Conditioning + FT839 + Rituximab with stable background therapy (Regimen F)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
Conditioning + FT839 (Regimen G)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
Conditioning + FT839 with stable background therapy (Regimen H)
FT839, allogeneic T cells targeting CD19 and CD38
干预措施: FT839 (Biological)
结局指标
主要结局
Phase 1: Incidence of Dose-limiting Toxicity, Adverse Events, and Serious Adverse Events
时间窗: From enrollment to the end of the post-treatment follow-up at 2 years
Incidence and severity of dose-limiting Toxicity (DLT)s, adverse event (AE)s, and serious adverse event (SAE)s
Phase 2: Change from baseline in Birmingham Vasculitis Activity Score
时间窗: From enrollment to the end of the post-treatment follow-up at 2 years
Birmingham Vasculitis Activity Score (BVAS) will be measured to evaluate the efficacy of FT839 in AAV. The BVAS score ranges from 0 to 63, with lower scores indicating better outcomes.
Phase 2: Change from baseline in Manual muscle testing-8
时间窗: From enrollment to the end of the post-treatment follow-up at 2 years
Manual muscle testing-8 (MMT-8) will be measured to evaluate the efficacy of FT839 in IIM. The MMT-8 score ranges from 0 to 150, with higher scores indicating better outcomes.
Phase 2: Change from baseline in Disease Activity Score using 28 joint counts and C-reactive protein (a composite measure)
时间窗: From enrollment to the end of the post-treatment follow-up at 2 years
Disease Activity Score using 28 joint counts and C-reactive protein (DAS28-CRP) will be measured to evaluate the efficacy of FT839 in RA. The validated composite measure DAS28-CRP score ranges from 0.0 to 9.4, with lower scores indicating better outcomes.
Phase 2: Change from baseline in SLE Disease Activity Index 2000
时间窗: From enrollment to the end of the post-treatment follow-up at 2 years
SLE Disease Activity Index 2000 (SLEDAI-2K) score will be measured to evaluate the efficacy of FT839 in SLE. The SLEDAI-2K score ranges from 0 to 105, with lower scores indicating better outcomes.
Phase 2: Change from baseline in Modified Rodnan skin score
时间窗: From enrollment to the end of the post-treatment follow-up at 2 years
Modified Rodnan skin (mRSS) score will be measured to evaluate the efficacy of FT839 in SSc. The mRSS score ranges from 0 to 51, with lower scores indicating better outcomes.
次要结局
- Phase 1: Maximum concentration and area under the curve of FT839 in peripheral blood(From enrollment to the end of the post-treatment follow-up at 2 years)
- Phase 2: Incidence of AEs and SAEs(From enrollment to the end of the post-treatment follow-up at 2 years)
- Phase 2: Cmax of FT839 in peripheral blood(From enrollment to the end of the post-treatment follow-up at 2 years)
- Phase 2: AUC of FT839 in peripheral blood(From enrollment to the end of the post-treatment follow-up at 2 years)