A Phase Ib, Open-label, Ascending Dose Study With Step-up Doses to Assess Safety, Tolerability, and Pharmacokinetics of PIT565 in Participants With Systemic Lupus Erythematosus (SLE).
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 11
- 主要终点
- Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
研究概览
简要总结
The purpose of the study is to determine the safety, tolerability, and pharmacokinetics of PIT565 in participants with SLE
详细描述
This is an open-label, ascending dose, uncontrolled study in participants with SLE systemic lupus erythematosus (SLE). PIT565 will be administered subcutaneously (s.c.) following premedication.
Up to 8 cohorts are planned. Every cohort will start with 3 sentinel participants and, depending on safety as well as observed biological activity, may have additional optional participants. The decision to escalate the dose from one cohort to the next will be based both on safety and PD data. After the identification of a dose level that has been declared safe and has induced predefined B cell depletion in 100% of the participants (candidate dose level), the cohort from this candidate dose level can be expanded with up to 12 additional participants (up to a total of 15 participants per cohort).
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
- •Diagnosis of SLE according to the 2019 ACR/EULAR criteria
- •Documentation of SLE autoantibodies
- •Active SLE disease, as demonstrated by a SLEDAI-2K ≥ 4 at screening
- •Failure to respond to standard-of-care medicines for the treatment of SLE as detailed in the protocol
- •Immunization against pneumococcus, meningococcus, influenza, and COVID-19
排除标准
- •Severe SLE-related organ damage dysfunction or life-threatening disease at screening.
- •Any acute, severe lupus-related flare during screening that needs immediate treatment such as acute CNS lupus (e.g., psychosis, epilepsy) or catastrophic antiphospholipid syndrome.
- •Presence of severe lupus kidney disease as defined by worsening proteinuria or estimated glomerular filtration rate (eGFR) which in the opinion of the Investigator requires immunosuppressive induction or maintenance treatment at screening.
- •History or current diagnosis of ECG or cardiac abnormalities indicating a significant risk of safety for participants.
- •Use of prohibited medication defined in the protocol.
- •Clinically significant active, opportunistic, chronic or recurrent infection (including, HIV, HBV, HCV) confirmed one month prior to or during screening.
- •Serious medical illness likely to interfere with participation in this clinical study.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Cohort 4
Dose level 4
干预措施: PIT565 (Drug)
Cohort 1
Dose level 1
干预措施: PIT565 (Drug)
Cohort 6
Dose level 6
干预措施: PIT565 (Drug)
Cohort 8
Dose level 8
干预措施: PIT565 (Drug)
Cohort 2
Dose level 2
干预措施: PIT565 (Drug)
Cohort 3
Dose level 3
干预措施: PIT565 (Drug)
Cohort 5
Dose level 5
干预措施: PIT565 (Drug)
Cohort 7
Dose level 7
干预措施: PIT565 (Drug)
结局指标
主要结局
Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
时间窗: From Study Day 1 until Study Day 180
Safety assessments of PIT565 including changes in vital signs, electrocardiograms (ECG) and laboratory results from baseline
次要结局
- Maximum Observed Blood Concentrations (Cmax)(From pre-dose Day 1 until Day 29)
- Presence/absence of Anti-drug Antibodies(From pre-dose Day 1 until Day 180)
- Maximum Observed Blood Concentrations (Cmax)(From pre-dose Day 1 until Day 29)
- Presence/absence of Anti-drug Antibodies(From pre-dose Day 1 until Day 180)