A Phase 1a/1b Randomized, Double-Blind, Placebo-Controlled, 3-Part Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Subcutaneous Doses of TRB-061 in Healthy Participants and in Patients With Moderate-to-Severe Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 115
- 试验地点
- 19
- 主要终点
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This Phase 1a/1b randomized, double-blind, placebo-controlled study evaluates the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneously (SC) administered TRB-061 in healthy adults and patients with moderate-to-severe atopic dermatitis (AD). The number of dosing cohorts may be increased or decreased in Part 1 (SAD) or Part 2 (MAD).
Part 1 (SAD): Healthy participants receiving single doses of TRB-061 or placebo.
Part 2 (MAD): Healthy participants receiving multiple doses (3 doses over 8 weeks) of TRB-061 or placebo.
Part 3 (Phase 1b): Participants with moderate-to-severe AD receiving repeated doses (4 doses over 12 weeks) of TRB-061 or placebo.
详细描述
Healthy adults will receive a single-ascending dose (SAD) of placebo or TRB-061 in cohorts of 8 (6 active, 2 placebo). Safety data will be reviewed before dosing the remaining participants. Follow-up lasts 12 weeks post-dosing. Treatment in the multiple-ascending dose (MAD) phase will be initiated after SAD cohort safety review is completed. Healthy adults will receive 3 doses of TRB-061 or placebo every 4 weeks (Q4W) over 8 weeks. Follow-up lasts 10 weeks post-last dose.
Participants with moderate-to-severe AD (Phase 1b) will be randomized to receive one of two dose levels of TRB-061 or placebo for 12 weeks (Q4W) in Period 1. In Period 2, participants will have the option to consent to a cross over treatment where those who previously received placebo will receive TRB-061 and those who received TRB-061 will receive placebo Q4W for 12 weeks followed by a Follow Up period through End of Study (EOS). Participants who do not consent to receive crossover treatment will continue study visits including efficacy and safety assessments through the EOS visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 是
入选标准
- •Male or female participants aged 18 to 70 years, inclusive, at the time of informed consent.
- •Body weight ≥50 kg and a body mass index (BMI)between 18.5 and 35.0 kg/m², inclusive.
- •Participant is in good general health as determined by the investigator, based on medical history, physical examination, and clinical laboratory tests.
- •For healthy participants (SAD and MAD): no clinically significant abnormalities in ECGs at screening.
- •For participants in Phase 1b: Confirmed diagnosis of AD with onset of symptoms at least 1 year prior to Screening.
- •Must be nonpregnant and nonlactating with negative pregnancy tests at screening and prior to dosing.
- •Must be a non-smoker or ≤5 cigarettes per week for the past 6 months (SAD/MAD only).
- •For participants in Phase 1b: Moderate-to-severe AD at Screening and at Day 1 visit
- •Agrees to abstain from the use of tetrahydrocannabinol (THC)-containing products while on study.
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the participant at risk or interfere with study results.
- •History or presence of any condition requiring systemic immunosuppressive or immunomodulatory therapy within a defined period before screening.
- •Use of any biologic agent (e.g., monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) before Day
- •Participation in another investigational drug trial within 30 days or 5 half-lives of the prior investigational product (whichever is longer) before Day
- •History of hypersensitivity or allergic reaction to any component of the study drug or placebo formulation.
- •Known active or latent tuberculosis (TB) infection. or history of incomplete TB treatment.
- •Positive test at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, or human immunodeficiency virus (HIV).
- •Active infection or history of serious infections within 4 weeks prior to Day
- •Clinically significant ECG abnormalities (e.g., QTcF>470 ms) or other cardiac risk factors.
- •Abnormal and clinically significant laboratory values at screening.
- •Use of live vaccines within 4 weeks before Day
- •Use of systemic corticosteroids, immunosuppressants, or immunomodulatory drugs within protocol-defined washout periods (Part 3 only).
- •Recent history of alcohol or drug abuse as defined per protocol.
- •Use of tobacco/nicotine products beyond protocol-allowed limits (SAD and MAD).
- •Positive cotinine test at check-in (SAD/MAD only).
- •Any other reason, in the opinion of the investigator or sponsor, that would make the participant unsuitable for participation in the study.
- •Any medical or psychiatric condition that, in the opinion of the Investigator or Sponsor's medical monitor, would place the participant at risk, interfere with study participation, or interfere with the interpretation of study results.
- •Surgery within the past 90 days prior to dosing as determined by the Investigator or Sponsor's medical monitor to be clinically relevant or planned surgery to be performed during the study and 30 days after the last dose of study drug
研究组 & 干预措施
SAD - TRB-061
Single ascending subcutaneous doses of TRB-061 in healthy participants
干预措施: TRB-061 (Drug)
Placebo Comparator
Subcutaneous placebo (matching TRB-061 in each study part)
干预措施: Placebo (Drug)
MAD - TRB-061
Multiple subcutaneous doses (Q4W for 8 weeks) in healthy participants
干预措施: TRB-061 (Drug)
Phase 1b - TRB-061
Multiple subcutaneous doses (Q4W for 12 weeks) in patients with moderate-to-severe AD
干预措施: TRB-061 (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Screening to Day 85 (Part 1), Up to Day 127 (Part 2); up to Day 337 (Part 3)
次要结局
- Pharmacokinetic (Maximum Observed Plasma Concentration, Cmax)(Up to Day 85 (Part 1), Up to Day 127 (Part 2); up to Week 49 (Part 3))