A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Sequential, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of AK006 in Healthy Subjects and in Subjects With H1 Antihistamine Refractory Chronic Spontaneous Urticaria
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Allakos Inc.
- 入组人数
- 136
- 试验地点
- 25
- 主要终点
- AEs leading to discontinuation
研究概览
简要总结
This is a Phase 1, randomized, double-blind, placebo-controlled, sequential, single- and multiple-ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of intravenous (IV) infusions and a single subcutaneous (SC) injection of AK006. The study will be conducted in 4 parts: a single-ascending dose part (Part A) in healthy participants, a multiple-ascending dose part (Part B) in healthy participants with an expanded cohort (Part C) in participants with chronic spontaneous urticaria (CSU), and a single ascending dose SC injection cohort (Part D) in healthy 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
- Double (Participant, Investigator)
盲法说明
Double-blind (placebo) essentially identical in appearance to the investigational drug (AK006)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •To be included in the study, the participant must:
- •Weigh between 60 and 120 kg (inclusive) and have a body mass index (BMI) between 20 and 32 kg/m2, inclusive
- •Agree (female of childbearing potential or male with female partner of childbearing potential) to use a highly effective method (<1% failure rate) of birth control, if sexually active from screening and for 16 weeks after the last dose of investigational product (IP).
- •Additionally, to be included in Part A, B and D, the participant must:
- •Be in good general health with no significant medical history and has no clinically significant abnormalities on physical examination
- •Additionally, to be included in Part C, the participant must:
- •Have a diagnosis of chronic spontaneous urticaria (CSU) for at least 6 months prior to screening
- •Has a diagnosis of moderate to severe CSU that is refractory to stable doses of a single 2nd or later generation H1-AH between 1× and 4× the licensed dose and frequency at the time of randomization as defined by the following:
- •Presence of hives and itch for ≥6 consecutive weeks at any time prior to the Screening, despite the use of non-sedating H1-AHs. Note: Subject must be on a non-sedating H1-AH for treatment of CSU symptoms at the time of the Screening visit.
- •UAS7 score ≥16 with a HSS7 score ≥8 for the 2 consecutive weeks prior to randomization (Day 1) while on the stable dose of an H1-AH.
- •Be on a stable dose of a single 2nd or later generation H1-antihistamines for the treatment of CSU, between 1× and 4× the licensed dose and frequency, by Day -14 of the Screening Period and must be willing to remain on the same stable dose throughout the study.
- •Able and willing to complete a daily electronic diary to collect CSU symptoms for the duration of the study.
排除标准
- •A participant who meets any of the following exclusion criteria will not be eligible for inclusion in the study:
- •Female participants who are pregnant, lactating, or planning to become pregnant during the study.
- •Abnormal laboratory values, or findings in physical examination, ECG (QTc >450 ms for males and >470 ms for females), or vital signs considered to be clinically significant by the investigator.
- •Additionally, a participant will be excluded from Part A, B and D, if:
- •Received treatment with any prescribed (excluding hormonal contraceptives or hormone replacement therapy [post-menopausal females]) or nonprescribed systemic or topical medication (including herbal product, and vitamins) within 21 days prior to the first dose of IP (excluding acetaminophen).
- •Additionally, a participant will be excluded from Part C, if:
- •Has known or suspected urticarial vasculitis
- •Subject has causes other than CSU for their urticaria including symptomatic dermographism, cholinergic urticaria, or any inducible urticaria
- •Subject has other conditions or diseases that in the investigator's opinion might influence study evaluations and results
- •Has any disease or condition (medical or surgical) which, in the opinion of the investigator, or medical monitor, would place the subject at increased risk
研究组 & 干预措施
Part A - Single Ascending Dose (SAD) Intravenous Cohorts
Part A: Healthy adult participants will receive a single intravenous infusion of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 5 cohorts evaluated.
干预措施: AK006-IV (Drug)
Part A - Single Ascending Dose (SAD) Intravenous Cohorts
Part A: Healthy adult participants will receive a single intravenous infusion of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 5 cohorts evaluated.
干预措施: Placebo-IV (Drug)
Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts
Part B: Healthy adult participants will receive multiple intravenous infusions of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 3 cohorts evaluated.
干预措施: AK006-IV (Drug)
Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts
Part B: Healthy adult participants will receive multiple intravenous infusions of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 3 cohorts evaluated.
干预措施: Placebo-IV (Drug)
Part C - Multiple Dose Intravenous Cohort
Part C: Adults with Chronic Spontaneous Urticaria will receive multiple intravenous infusions of AK006 or matching placebo.
干预措施: AK006-IV (Drug)
Part C - Multiple Dose Intravenous Cohort
Part C: Adults with Chronic Spontaneous Urticaria will receive multiple intravenous infusions of AK006 or matching placebo.
干预措施: Placebo-IV (Drug)
Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts
Part D: Healthy adult participants will receive a single subcutaneous injection of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 2 cohorts evaluated.
干预措施: AK006-SC (Drug)
Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts
Part D: Healthy adult participants will receive a single subcutaneous injection of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 2 cohorts evaluated.
干预措施: Placebo-SC (Drug)
结局指标
主要结局
AEs leading to discontinuation
时间窗: Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)
AEs
Incidence of clinically significant abnormal laboratory values, electrocardiograms (ECGs), and vital signs
时间窗: Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)
Incidence of clinically significant abnormal laboratory values, electrocardiograms (ECGs), and vital signs
Incidence and severity of adverse events (AEs)
时间窗: Screening to Day 113 (Part A and D), Screening to Day 141 (Part B), and Screening to Day 197 (Part C)
AEs, serious AEs, and treatment emergent AEs (AE that starts after start of investigational product)
Incidence of AEs of special interest
时间窗: Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)
Infusion-related reactions, injection-related reactions, injection site reactions, anaphylaxis, and opportunistic infections
次要结局
- AK006 serum concentration at end of IV infusion(Day 1 (Part A) and Day 29 (Part B))
- AK006 area under the concentration-time curve (AUC) from time 0 to the time of last quantifiable concentration (AUC[0-last])(Day 1 to Day 113 (Part A and D) and Day 29 to Day 141 (Part B))
- AK006 AUC from time 0 extrapolated to infinity (AUC[0-inf])(Day 1 to Day 113 (Part A and D))
- Total systemic clearance of AK006 after intravenous or subcutaneous dose (CL)(Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B))
- Systemic steady-state volume of distribution (Vss) of AK006(Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B))
- AK006 Terminal elimination phase half-life (t1/2)(Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B))
- Predose AK006 serum concentration (Ctrough, before the next dose) (Part B)(Day 29 (pre-dose))
- AK006 AUC(0-last) after the second dose (Part B)(Day 29 to Day 141)
- AK006 AUC over the dosing time interval (time 0 to 28 days) (AUC[tau]) (Part B)(Day 1 to Day 28 with each dosing interval)
- AK006 serum concentrations(Up to Day 141 (Part A, B, D); Up to Day 197 (Part C))
- AK006 absolute bioavailability subcutaneous injection(Day 1 to Day 113 (Part A and D))
- AK006 PK dose proportionality (Part A, B, D)(Up to Day 141)
- AK006 PK dose stationarity (Part B)(Up to Day 141)
- AK006 Anti-drug Antibodies (ADAs)(Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B) and Day 1 to Day 197 (Part C))