A Randomized, Adaptive, Investigator/ Subject Blind, Single Ascending Dose, Placebo-Controlled Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered RO7049665 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Percentage of Participants with Adverse Events
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of single ascending doses of subcutaneous (SC) injections of RO7049665 in healthy volunteers. In addition, pharmacokinetics (PK) of RO7049665, the effects of single doses of RO7049665 on regulatory T-cells as well as the single dose immunogenicity of RO7049665 will be evaluated. This trial plans to evaluate approximately seven single dose-levels of RO7049665 or matching-placebo during dose-escalation in approximately 40 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male healthy volunteers, 18 to 45 years of age, inclusive;
- •Absence of evidence of any active or chronic disease;
- •Body mass index (BMI) of 18-30 kilograms per square meter (kg/m^2), inclusive;
- •Contraception requirements: refrain from heterosexual intercourse or use contraceptive measures, and agreement to refrain from donating sperm.
排除标准
- •History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis;
- •Clinically significant abnormalities (as judged by the Investigator) in laboratory test results;
- •Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study;
- •History of hypersensitivity to biologic agents or any of the excipients in the formulation;
- •Any abnormal skin conditions or potentially obscuring tattoos, pigmentation or lesions in the area intended for subcutaneous injection;
- •Prior administration of aldesleukin, or interleukin-2 (IL-2) derivatives.
研究组 & 干预措施
Placebo
Participants will be administered a single SC dose of matching placebo formulation administered in up to 4 SC injections.
干预措施: Placebo (Biological)
RO7049665
Participants will be administered a single SC dose of RO7049665 administered in up to 4 SC injection.
干预措施: RO7049665 (Biological)
结局指标
主要结局
Percentage of Participants with Adverse Events
时间窗: From baseline up to approximately 8 weeks
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
次要结局
- PK: Area Under the Concentration-Time Curve (AUC) from Time 0 to Time of Last Sampling of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)
- PK: Time to Maximum Concentration (Tmax) of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)
- PK: AUC from Time 0 to Time tau (AUC0-t) of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)
- PK: Half-life (t1/2) of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)
- PK: Apparent Volume of Distribution (Vz/F) of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)
- PK: AUC from Time 0 to infinity (AUCinf) of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)
- PK: Apparent Clearance (CL/F) of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)
- Change from Baseline in Regulatory T Lymphocyte (Tregs) Count(Day -1, Pre-dose Day 1; post-dose Day 2, 3, 4, 6, 8, 12, 15, 29, up to follow-up visit (Day 57))
- Percentage of Participants with Anti-Drug Antibodies(Pre-dose Day 1, post-dose Day 8, 15, 29, up to follow-up visit (Day 57))
- PK: Maximum Serum Concentration Observed (Cmax) of RO7049665(Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43)