A Phase 1a, Open-Label, First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KT501 by a Single Subcutaneous Administration in Participants With Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
This is a Phase 1, open-label, first-in-human study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of KT501 administered subcutaneously to participants with Rheumatoid Arthritis (RA).
详细描述
This is a Phase 1, open-label, first-in-human dose escalation study to investigate the safety, tolerability, pharmacokinetic and pharmacodynamic of KT501 by a single subcutaneous administration in participants with Rheumatoid Arthritis (RA).
Up to a total of 5 cohorts with up to approximately 24 participants in total with RA will be enrolled. All participants will receive a single dose of KT501 on Day 1 and followed up until Week 12. For any participants with B cells lower than baseline level or lower limit quantification, whichever is lower, additional B cell follow up is required up to Week 48 after the study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •18 to 75 years old
- •Diagnosis of adult-onset RA for at least 6 months
- •Moderately to severely active RA
- •Inadequate treatment response as defined in the protocol
- •RF + or ACPA+
- •Stable use of traditional DMARDs is permitted
- •Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
排除标准
- •Functional class IV as defined by the ACR Classification of Functional Status in RA
- •Presence of any concomitant autoimmune disease other than RA
- •Active infection, history of serious recurrent or chronic infection
- •History of progressive multifocal leukoencephalopathy
- •Have a diagnosis or history of malignant disease within 5 years or breast cancer diagnosed within the previous 10 years.
- •History of or planned organ transplant and/or autologous or allogeneic hematopoietic stem cell transplantation
- •Receipt of live vaccine within 4 weeks
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after study
- •Women who are pregnant or breastfeeding
- •Significant or uncontrolled medical disease that would preclude participant participation
研究组 & 干预措施
Dose Level 1
KT501 Subcutaneous Injection Dose Level 1
干预措施: KT501 (Drug)
Dose Level 2
KT501 Subcutaneous Injection Dose Level 2
干预措施: KT501 (Drug)
Dose Level 3
KT501 Subcutaneous Injection Dose Level 3
干预措施: KT501 (Drug)
Dose Level 4
KT501 Subcutaneous Injection Dose Level 4
干预措施: KT501 (Drug)
Dose Level 5
KT501 Subcutaneous Injection Dose Level 5
干预措施: KT501 (Drug)
结局指标
主要结局
Incidence of Adverse Events
时间窗: From Baseline Up to 12 weeks
Incidence and severity of Adverse Events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Incidence of Cytokine-release Syndrome (CRS)
时间窗: From Baseline Up to 12 Weeks
Incidence and severity of CRS with severity determined according to the 2019 American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus grading criteria
Changes in Pulse Rate from Baseline
时间窗: From Baseline Up to 12 Weeks
Vital signs: Changes in Pulse Rate from Baseline
Changes in Respiratory Rate from Baseline
时间窗: From Baseline to 12 Weeks
Vital Signs: Changes in Respiratory Rate from Baseline
Changes in Blood Pressure from Baseline
时间窗: From Baseline Up to Week 12
Vital Signs: Changes in Blood Pressure from Baseline
Changes in Temperature from Baseline
时间窗: From Baseline to 12 Weeks
Vital Signs: Changes in Body Temperature from Baseline
Changes in Hematology Clinical Laboratory Results from Baseline
时间窗: From Baseline Up to 12 Weeks
Hematology: Changes in results from Baseline
Changes in Chemistry Clinical Laboratory Results from Baseline
时间窗: From Baseline Up to 12 Weeks
Chemistry: Changes in results from Baseline
Changes in Urinalysis Clinical Laboratory Results from Baseline
时间窗: From Baseline Up to 12 Weeks
Urinalysis: Changes in results from Baseline
Changes in Coagulation Clinical Laboratory Results from Baseline
时间窗: From Baseline Up to 12 Weeks
Coagulation: Changes in results from Baseline
次要结局
- Serum Concentrations of KT501(Pre-dose and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85.)
- Incidence of Treatment-induced Anti-Drug Antibodies (ADAs)(Pre-dose and on Day 1; Day 8, 11, 15, 22, 29, 43, 57 and 85.)
- To Determine Cmax(Day 1 - Day 85)
- To Determine Tmax, Derived from Serum Concentration of each Dose of KT501(Day 1 - Day 85)
- Area Under the Serum-concentration Time Curve (AUC) from Time Zero to the Last Timepoint with Measurable Analyte Concentration (AUC0-t)(Day 1 - Day 85)
- AUC from Time Zero to Infinity (AUCinf)(Day 1 - Day 85)
- To Determine Terminal Half-Life (T1/2)(Day 1 - Day 85)
- Total Body Clearance (CL/F)(Day 1 - Day 85)
- Volume of Distribution During the Terminal Phase (Vz/F)(Day 1 - Day 85)
- Change in Levels of B Cell Count(Pre-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85.)
- Duration of B Cell Depletion(Day 1 - Day 85)
- Change in Levels of Acute Inflammatory Markers(Pre-dose and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 15, 22, 29,, 57 and 85.)
- Changes in Blood Pressure from Baseline(From Baseline to 12 Weeks)