Phase 1b/2a Prospective, Open Label, Multicenter, Single Arm Study to Assess Safety, Efficacy and Persistence of ACE1831, in Subjects With Immunoglobulin G4-Related Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- To assess the safety and tolerability of ACE1831 in subjects with IgG4-RD
研究概览
简要总结
ACE1831 is an off-the-shelf, allogeneic gamma delta T (gdT) cell therapy derived from healthy donors, that is under investigation for the treatment in subjects with Immunoglobulin G4 Related Disease (IgG4-RD)
详细描述
ACE1831-201 study is an Open Label, Multicenter, Single Arm Study to Assess Safety, Efficacy and Persistence of ACE1831, in Subjects with Immunoglobulin G4-Related Disease
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for this study, all of the following inclusion criteria must be met:
- •Signed Informed Consent
- •Male or female ≥ 18 to 75 years of age
- •Active IgG4-RD flare at screening with IgG4-RD Responder Index at least 2, confirmed by symptoms, labs, and/or imaging.
- •History of IgG4-RD involving at least 2 organs/sites, and current flare involves at least 1 organ/site (excluding lymph nodes) requiring treatment.
- •Elevated serum IgG4 above the upper limit of normal at screening.
- •Able to receive glucocorticoids for current flare and taper to 0 mg by Day -
- •Contraception agreement per protocol from screening through 24 weeks after last ACE1831 dose (no LDC) or 12 months after last LDC dose (with LDC).
- •For sites in China only: prior treatment failure to glucocorticoids and at least one immunosuppressive agent.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this trial.
- •Significant conditions that impair ability to receive study treatment or comply.
- •Predominant fibrosis in affected organs.
- •Active/latent infection that would interfere with therapy (including HBV, HCV, HIV, TB, syphilis) or significant recent infection per protocol.
- •Known immunodeficiency state.
- •NYHA class III/IV heart disease.
- •Severe allergy/hypersensitivity to monoclonal antibodies or relevant study agents.
- •Malignancy within 5 years (protocol exceptions apply).
- •Recent investigational agent exposure.
- •Recent B-cell depleting therapy (anti-CD20/anti-CD19) unless reconstitution per protocol.
- •Live/attenuated vaccine within 2 months.
- •Pregnant or breastfeeding.
- •Inadequate organ function/blood counts per protocol.
研究组 & 干预措施
Single Arm trial
The single, open label study arm includes 3 dose escalation cohorts:
-
Cohort 1:
-
Cohort 1a: Receives ACE1831 (Dose Level 1) with lymphodepletion conditioning (LDC)
-
Cohort 1b: Receives ACE1831 (Dose Level 1) without LDC.
-
Cohort 2: Receives ACE1831 (Dose Level 2) with or without LDC depending on assignment
-
Cohort 3: Receives ACE1831 (Dose Level 3) with or without LDC depending on assignment
干预措施: ACE1831 (Drug)
Single Arm trial
The single, open label study arm includes 3 dose escalation cohorts:
-
Cohort 1:
-
Cohort 1a: Receives ACE1831 (Dose Level 1) with lymphodepletion conditioning (LDC)
-
Cohort 1b: Receives ACE1831 (Dose Level 1) without LDC.
-
Cohort 2: Receives ACE1831 (Dose Level 2) with or without LDC depending on assignment
-
Cohort 3: Receives ACE1831 (Dose Level 3) with or without LDC depending on assignment
干预措施: Lymphodepleting chemotherapy (Drug)
结局指标
主要结局
To assess the safety and tolerability of ACE1831 in subjects with IgG4-RD
时间窗: up to 72 weeks post last-ACE1831 dose
* To assess the incidence of Adverse Events (AEs), \[AEs including Treatment Emergent AEs, Serious AEs (SAEs), AEs of Special Interests (AESIs), and dose limiting toxicities (DLTs)\] (unit: number of AEs) * To assess number of subjects with clinically significant changes in clinical laboratory tests from baseline (unit: number of subjects) * To assess number of subjects with clinically significant changes in physical examination results from baseline (unit: number of subjects) * To assess number of subjects with clinically significant changes in electrocardiograms (ECGs) results (combined assessment of PR, QRS, QT, and QTcF interval, and heart rate) from baseline (unit: number of subjects) * To assess number of subjects with clinically significant changes in vital signs (temperature, respiratory rate, heart rate, blood pressure, heart rate, and Sp02) from baseline (unit: number of subjects)
Safety and Tolerability of ACE1831 as Assessed by Adverse Events, Clinical Laboratory Tests, Physical Examinations, ECGs, and Vital Signs
时间窗: up to 72 weeks post last-ACE1831 dose
Primary Outcome Measures: Safety and Tolerability of ACE1831. Adverse Events: Incidence of TEAEs, SAEs, AESIs, and DLTs. Clinical Laboratory Abnormalities: Number of subjects with clinically significant abnormalities in protocol-defined clinical laboratory assessments compared with baseline. Physical Examination Abnormalities: Number of subjects with clinically significant changes from baseline. ECG Abnormalities: Number of subjects with clinically significant ECG changes (PR, QRS, QT/QTcF, heart rate) from baseline. Vital Signs Abnormalities: Number of subjects with clinically significant changes from baseline. Number of Subjects With Clinically Significant Changes in Vital Signs From Baseline. Number of subjects with clinically significant changes in vital signs, including temperature, respiratory rate, heart rate, blood pressure, and oxygen saturation (SpO₂), compared with baseline. For all of the above, Unit of Measure: Number of Subjects
次要结局
- To assess the efficacy of ACE1831 (primary efficacy)(24 weeks after last dose of ACE1831)
- 3.1 To assess the efficacy of ACE1831 (secondary efficacy): Proportion of subjects who experience sustained complete remission(up to 72 weeks post-last ACE1831 dose)
- 3.2 To assess the efficacy of ACE1831 (secondary efficacy): Time to first flare(up to 72 weeks post-last ACE1831 dose)
- 3.3 To assess the efficacy of ACE1831 (secondary efficacy): Cumulative GC usage(up to 72 weeks post-last ACE1831 dose)
- 3.4 To assess the efficacy of ACE1831 (secondary efficacy): Changes in SF-12(up to 72 weeks post-last ACE1831 dose)
- 3.5 To assess the efficacy of ACE1831 (secondary efficacy): Changes in PGA(up to 72 weeks post-last ACE1831 dose)
- 3.6 To assess the efficacy of ACE1831 (secondary efficacy): Time to PGA = 0(up to 72 weeks post last-ACE1831 dose)
- 3.7 To assess the efficacy of ACE1831 (secondary efficacy): Changes in SGA(up to 72 weeks post last-ACE1831 dose)
- 3.8 To assess the efficacy of ACE1831 (secondary efficacy): Changes in SSI(up to 72 weeks post last-ACE1831 dose)
- 3.9 To assess the efficacy of ACE1831 (secondary efficacy): Changes in IgG4-RD RI(up to 72 weeks post last-ACE1831 dose)