A Phase 1/1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single and Multiple Ascending Doses of BCX17725 in Healthy Participants and Multiple Doses of BCX17725 in Participants With Netherton Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 14
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a first-in-human, Phase 1/1b, 4-part study that includes the evaluation of safety, tolerability, pharmacokinetics (PK), and immunogenicity of BCX17725 when administered via single and multiple doses in healthy adult participants (Parts 1 and 2), and multiple doses in adult participants with Netherton syndrome (Part 3). In Part 4, the effectiveness, safety, and tolerability of BCX17725 when administered via multiple IV and/or SC doses through 12 weeks will be evaluated in adult and adolescent participants with Netherton syndrome.
详细描述
Parts 1 and 2 are randomized, placebo-controlled, single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study parts, respectively, in healthy participants. Part 3 will evaluate multiple dose administrations in participants with Netherton syndrome in an open-label design. Part 4 will evaluate multiple administrations of BCX17725 in participants with Netherton syndrome in an open-label study design over 12 weeks, with an 8-week post-treatment follow-up period.
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
- Double (Participant, Investigator)
盲法说明
Parts 1 and 2 will be blinded; Parts 3 and 4 will be open label
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or non-pregnant, non-lactating female aged 18 to 55 years, inclusive (Parts 1 and 2), 18 to 65 years, inclusive (Part 3), or 12 to 65 years, inclusive (Part 4)
- •Confirmed diagnosis of Netherton syndrome (Parts 3 and 4)
- •IGA score of ≥ 3 (Parts 3 and 4) and IASI score of ≥ 16 (Part 4)
- •BMI between 18 and 30 kg/m^2, inclusive (Parts 1 and 2)
- •Estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min/1.73 m^2 (Parts 1 and 2) or ≥ 60 mL/min/1.73 m^2 (Part 3)
- •Agree to follow the protocol contraception requirements from screening until 90 days after the last dose of study drug
- •In the opinion of the investigator, expected to adequately comply with all required study procedures and restrictions for the duration of the study
排除标准
- 未提供
研究组 & 干预措施
Part 1 - placebo single dose
Participants randomized to placebo will receive placebo as a single dose
干预措施: Placebo (Drug)
Part 1 - BCX17725 single dose
Participants randomized to BCX17725 will receive BCX17725 as a single dose in sequential ascending dose cohorts
干预措施: BCX17725 (Drug)
Part 2 - BCX17725 multiple doses
Participants randomized to BCX17725 will receive BCX17725 as multiple doses in sequential ascending dose cohorts
干预措施: BCX17725 (Drug)
Part 4 - BCX17725 multiple doses
Participants will receive BCX17725 as multiple doses
干预措施: BCX17725 (Drug)
Part 2 - placebo multiple doses
Participants randomized to placebo will receive placebo as multiple doses
干预措施: Placebo (Drug)
Part 3 - BCX17725 multiple doses
Participants will receive BCX17725 as multiple doses
干预措施: BCX17725 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: From screening through EOS (ie, through Day 78 in Parts 1 and 3, and Day 106 in Part 2)
Incidence of TEAEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) from screening through end-of-study (EOS) in each study part
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: From screening through EOS (ie, through Day 78 in Parts 1 and 3, and Day 106 in Part 2)
Incidence of TEAEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) from screening through end-of-study (EOS) in each study part
Change from baseline in Ichthyosis Area and Severity Index (IASI) score at Week 12 (Part 4)
时间窗: From baseline to Week 12
IASI measures the severity of erythema (IASI-E) and scaling (IASI-S); the maximum sub-scores for the IASI-E and IASI-S being 24, and the maximum total IASI score being 48. Higher scores indicate worse clinical outcome.
次要结局
- Maximum observed serum concentration (Cmax)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Time to maximum observed serum concentration (Tmax)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Area under the serum concentration-time curve (AUC) from time 0 to the time of last measurable concentration (AUC0-t)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Terminal elimination half-life (t1/2)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Number of participants who are anti-drug antibody (ADA)-positive (baseline and post-baseline) and number of participants who have treatment-emergent ADAs(Day 1 pre-dose and up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Maximum observed serum concentration (Cmax)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Time to maximum observed serum concentration (Tmax)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Area under the serum concentration-time curve (AUC) from time 0 to the time of last measurable concentration (AUC0-t)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Terminal elimination half-life (t1/2)(Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Number of participants who are anti-drug antibody (ADA)-positive (baseline and post-baseline) and number of participants who have treatment-emergent ADAs(Day 1 pre-dose and up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3))
- Change from baseline in Investigator Global Assessment (IGA) score at Week 12 (Part 4)(From baseline to Week 12)
- Change from baseline in Worst Itch Numerical Rating Score (NRS) at Week 12 (Part 4)(From baseline to Week 12)
- Incidence of TEAEs (Part 4)(From baseline through Week 20)
- Serum concentrations of BCX17725 (Part 4)(From baseline through Week 20)