A Phase 1, Randomized, Double-Blind, Vehicle-Controlled Ascending Doses Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ASN008 Topical Gel in Healthy Volunteers and Subjects With Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 5
- 主要终点
- Evaluate safety and tolerability of ASN008 topical gel to define a maximum tolerated dose (Part A and B)
研究概览
简要总结
This is an ascending dose escalation study to test the safety, tolerability and preliminary efficacy of ASN008 TG in first-in-human subjects
详细描述
This is a two part, randomized, blinded, vehicle-controlled study to determine a safe and tolerable dose of ASN008 TG. Part A will asses a single ascending dose of ASN008 TG in cohorts of healthy volunteers, while Part B will assess multiple ascending doses of TG, to be determined (TBD) based on Part A safety and tolerability, in patients with mild-to-moderate dermatitis. Results from Part A and B will characterize safety, tolerability and pharmacokinetics. Part B patients will be assessed for changes in pruritus based on a numerical rating scale (NRS) of pruritus at baseline and on Day 15.
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
- Double (Participant, Investigator)
盲法说明
Part A: Double blinded, with exception of unblinded dispensing pharmacist Part B: Double blinded
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
- •Part A - Healthy Volunteers:
- •Written informed consent obtained prior to any required study-related procedure
- •Healthy female or male subject aged 18 to 65
- •Willing to use medically effective methods of birth control
- •Females of reproductive potential must have a negative serum pregnancy test at screening and negative serum or urine pregnancy test prior to first study drug application on Day 1
- •Non-smoker (no nicotine products for at least 6 months prior to screening)
- •BMI ≥18.5 kg/m2 and ≤32.0 kg/m2 with minimum weight of 60 kg
- •Part B- Subjects with AD:
- •Written informed consent obtained prior to any required study-related procedure
- •Confirmed diagnosis of active atopic dermatitis (AD)
- •History of AD for at least 6 months prior to Day 1 with an investigator global assessment ≥3 and body surface area covered with 1-10% AD
- •Pruritus score (NRS)≥ 5 at screening and NRS ≥7 on Day 1
排除标准
- •Both Part A and Part B:
- •Pregnant or breast-feeding women
- •Skin disease that may interfere with study assessments
- •Febrile illness within 6 days prior to Day 1, history of cancer within 5 years of Day 1, major surgery within 8 weeks prior to Day1, known immunodeficiencies, positive for hepatitis B or C or HIV infection
- •Significant medical/surgical history or condition or current physical/laboratory/ECG/ vitals signs abnormality that might compromise the subject
- •Corrected QT duration ≥450 milliseconds or other significant ECG abnormality
- •Received marketed or investigational biological agent within 12 weeks prior to Day 1 or JAK inhibitor or nonbiological product or device within 4 weeks of Day 1 or within 8 weeks of Day 1 if investigational product used or any drug/ substance that is a strong inhibitor or inducer of CYP3A4 or CYP2D6
- •Suspected hypersensitivity/allergy to lidocaine
- •Significant drug or alcohol abuse or mental illness in 2 years prior to Day 1
- •Part A Only- Healthy Volunteers:
- •Used medications or skin emollients within 2 weeks prior to Day 1 unless approved by investigator and sponsor
- •Part B Only - Subjects with AD:
- •Has infected atopic dermatitis
- •Used dupilumab 12 weeks prior to Day 1
- •Used doxepin, hydroxyzine or diphenhydramine, urea containing topical products within 1 week prior to Day 1
- •Used systemic antibiotics or topical medicated treatment or other systemic treatments that could affect AD 2 weeks prior to Day 1
- •Received any UV-B phototherapy, excimer laser treatment or psoralen-UV-A treatment within 4 weeks prior to Day 1
研究组 & 干预措施
82 µg/cm2 ASN008 TG or Placebo
PART A: ASN008 TG 82 µg/cm2 single application in 7 days or Placebo TG (6 subjects ASN008: 2 subjects placebo) (6:2)
干预措施: Placebo TG (Drug)
164 µg/cm2 ASN008 TG or Placebo
PART A: ASN008 TG 164 µg/cm2 single application in 7 days or Placebo (6:2)
干预措施: ASN008 TG (Drug)
164 µg/cm2 ASN008 TG or Placebo
PART A: ASN008 TG 164 µg/cm2 single application in 7 days or Placebo (6:2)
干预措施: Placebo TG (Drug)
82 µg/cm2 ASN008 TG or Placebo
PART A: ASN008 TG 82 µg/cm2 single application in 7 days or Placebo TG (6 subjects ASN008: 2 subjects placebo) (6:2)
干预措施: ASN008 TG (Drug)
328 µg/cm2 ASN008 TG or Placebo
Part A: ASN008 TG 328 µg/cm2 single application in 7 days or Placebo (6:2)
干预措施: ASN008 TG (Drug)
328 µg/cm2 ASN008 TG or Placebo
Part A: ASN008 TG 328 µg/cm2 single application in 7 days or Placebo (6:2)
干预措施: Placebo TG (Drug)
492 µg/cm2 ASN008 TG or Placebo
Part A: ASN008 TG 492 µg/cm2 single application in 7 days or Placebo (6:2)
干预措施: ASN008 TG (Drug)
492 µg/cm2 ASN008 TG or Placebo
Part A: ASN008 TG 492 µg/cm2 single application in 7 days or Placebo (6:2)
干预措施: Placebo TG (Drug)
ASN008 TG TBD Cohort 1 or Placebo
Part B: ASN008 TG Cohort 1 daily application for 15 days or Placebo (9 subjects ASN008: 3 subjects Placebo) (9:3)
干预措施: ASN008 TG (Drug)
ASN008 TG TBD Cohort 1 or Placebo
Part B: ASN008 TG Cohort 1 daily application for 15 days or Placebo (9 subjects ASN008: 3 subjects Placebo) (9:3)
干预措施: Placebo TG (Drug)
ASN008 TG TBD Cohort 2 or Placebo
Part B: ASN008 TG Cohort 2 daily application for 15 days or Placebo (9:3)
干预措施: ASN008 TG (Drug)
ASN008 TG TBD Cohort 2 or Placebo
Part B: ASN008 TG Cohort 2 daily application for 15 days or Placebo (9:3)
干预措施: Placebo TG (Drug)
ASN008 TG TBD Cohort 3 or Placebo
Part B: Placebo TG Cohort 3 daily application for 15 days or Placebo (9:3)
干预措施: ASN008 TG (Drug)
ASN008 TG TBD Cohort 3 or Placebo
Part B: Placebo TG Cohort 3 daily application for 15 days or Placebo (9:3)
干预措施: Placebo TG (Drug)
结局指标
主要结局
Evaluate safety and tolerability of ASN008 topical gel to define a maximum tolerated dose (Part A and B)
时间窗: Part A: 14 days; Part B: 22 days
Analyze incidence of treatment-emergent adverse events (TEAE)
次要结局
- Change from baseline in pruritus NRS in AD subjects (Part B)(22 days)
- Calculate the Pharmacokinetic maximum concentration (Part A and B)(7 days and 16 days)
- Calculate area under the plasma concentration versus time curve (Part A and B)(7 days and 16 days)
- Calculate the Pharmacokinetic Half-life (Part A and B)(7 days and 16 days)
- Change from baseline in Eczema Area and Severity Score (EASI) in AD subjects (Part B)(22 days)
- Change from baseline in Investigator Global Assessment Score in AD subjects (Part B)(22 Days)