Phase 1a/1b Randomized Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single- and Multiple-Ascending Doses and Food Effect of BGB-45035 in Healthy Participants and Its Safety and Tolerability in Patients With Autoimmune Dermatological Diseases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 203
- 试验地点
- 19
- 主要终点
- Parts A-D: Number of participants with clinically significant changes from baseline in clinical laboratory values
研究概览
简要总结
This study is the first-in-human (FIH) study of BGB-45035. The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BGB-45035 with both a single dose and multiple doses administered at different dose levels in healthy participants, followed by a Part E to evaluate the safety and tolerability of BGB-45035 in adults with autoimmune dermatological diseases like atopic dermatitis (AD) and prurigo nodularis (PN). An additional biomarker cohort will be evaluated in Part F.
Study details include:
- The study duration will be up to 24 months.
- The treatment duration will be up to 14 days for Parts A-D, up to 12 weeks for Part E, and up to 3 weeks for Part F.
- Safety follow-up 30 days after last dose of study drug.
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, Care Provider)
盲法说明
The cohorts in Part A, B, and C will be double-blinded, while Parts D, E, and F will be open-label.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for Parts A-D and Part F:
- •Female or male participants between the ages of 18 and 55 years inclusive (ages 18 and 45 years for Part C).
- •BMI of 18 to 32 kg/m^2; and a total body weight > 50 kg (110 lbs).
- •Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- •Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for 90 days after the last dose of study drug.
- •Female participants of childbearing potential can only join Part F and must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for 90 days after the last dose of study drug. They must also have a negative urine pregnancy test at baseline before first dose of study drug.
- •Inclusion Criteria for Part E
- •Female or male participants between the ages of 18 to 75 years of age.
- •Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for 90 days after the last dose of study drug. They must also have a negative urine pregnancy test at baseline before first dose of study drug.
- •AD Cohort E1:
- •Chronic AD diagnosed by the Eichenfield revised criteria of Hannifin and Rajka that has been present for at least 1 year before the Screening Visit.
- •Prior to baseline assessment, participants with AD must have used only nonmedicated topical emollients twice daily for at least 7 days, without any active ingredients or additives that could impact AD treatment (such as hyaluronic acid, urea, ceramide, or filaggrin degradation products). Participant's response to treatment must have remained inadequate at baseline. Additionally, the participant must be willing and able to adhere to standardized background topical therapy as outlined in the protocol throughout the remainder of the study.
- •PN Cohort E2:
- •Diagnosed as PN by a dermatologist for at least 3 months before the Screening Visit with prurigo lesions on upper limbs with or without lesions on the trunk or lower limbs.
- •Minimum of 20 PN lesions in total on either of the following: both legs, both arms, and/or the trunk at the Screening Visit and on Day
- •General Inclusion Criteria:
- •1. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps, or other ultraviolet light sources during the study.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- •Any condition possibly affecting drug absorption (eg, gastrectomy or cholecystectomy).
- •Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product, whichever is longer.
- •12-lead ECG demonstrating QTcF > 450 milliseconds.
- •Clinically significant abnormality on chest radiograph performed at screening or within 3 months of screening date.
- •History of tuberculosis or active or latent or inadequately treated infection, positive IGRA tests
- •Herbal supplements (including St. John's Wort) and hormone replacement therapy must be discontinued 14 days prior to the first dose of study medication.
- •Vaccination with live virus, attenuated live virus, or any live viral components within the 6 weeks prior to the first dose of study drug or is to receive these vaccines at any time during treatment or within 8 weeks following completion of study treatment.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part A (Single Ascending Dose)
Part A is designed to assess the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic profile of BGB-45035 following single-ascending doses (SAD) in healthy participants.
干预措施: Placebo (Drug)
Part B (Multiple Ascending Dose)
Part B is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy participants.
干预措施: Placebo (Drug)
Part C (Chinese Substudy)
Part C is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy Chinese participants.
干预措施: Placebo (Drug)
Part F (Biomarker Cohort)
Part F is designed to assess the pharmacodynamic activity of BGB-45035 in the skin of healthy volunteers.
干预措施: BGB-45035 (Drug)
Part C (Chinese Substudy)
Part C is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy Chinese participants.
干预措施: BGB-45035 (Drug)
Part D (Food Effect)
Part D is designed to assess the effect of food on BGB-45035 exposure.
干预措施: BGB-45035 (Drug)
Part E (PN Cohort E2)
PN Cohort E2 is designed to assess the safety, tolerability, and efficacy of a targeted dose of BGB-45035 in participants with moderate to severe PN.
干预措施: BGB-45035 (Drug)
Part A (Single Ascending Dose)
Part A is designed to assess the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic profile of BGB-45035 following single-ascending doses (SAD) in healthy participants.
干预措施: BGB-45035 (Drug)
Part B (Multiple Ascending Dose)
Part B is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy participants.
干预措施: BGB-45035 (Drug)
Part E (AD Cohort E1)
AD Cohort E1 is designed to assess the safety, tolerability, and efficacy of a selected dose of BGB-45035 in participants with moderate to severe AD.
干预措施: BGB-45035 (Drug)
结局指标
主要结局
Parts A-D: Number of participants with clinically significant changes from baseline in clinical laboratory values
时间窗: Baseline and up to approximately 1 month
Laboratory values include hematology, clinical chemistry, coagulation, and urinalysis
Parts A-D: Number of participants with clinically significant changes from baseline in vital signs
时间窗: Baseline and up to approximately 1 month
Vital signs include blood pressure and pulse rate
Parts A-D: Number of participants with clinically significant changes from baseline in cardiac conduction intervals
时间窗: Baseline and up to approximately 1 month
As assessed via 12-lead electrocardiogram (ECG)
Number of Participants Experiencing Adverse Events (AEs) in Parts A-E
时间窗: From the first dose of study drug to 30 days after the last dose; up to approximately 44 days for Parts A-D and up to 16 weeks for Part E
次要结局
- Parts A & D: Area under the plasma concentration time curve from time zero to last quantifiable time (AUClast) of BGB-45035(Up to approximately 14 days)
- Parts A & D: Area under the plasma concentration time curve from time zero to infinite time (AUCinf) of BGB-45035(Up to approximately 14 days)
- Parts B & C: Area under the plasma concentration time curve from time zero to end of dosing interval (AUCtau) of BGB-45035(Up to approximately 14 days)
- Parts A, B, C & D: Maximum observed plasma concentration (Cmax) of BGB-45035(Up to approximately 14 days)
- Parts A, B, C & D: Time to maximum plasma concentration (Tmax) of BGB-45035(Up to approximately 14 days)
- Parts B & C: Trough plasma concentration (Ctrough) of BGB-45035(Up to approximately 14 days)
- Parts A, B, C & D: Half life (t½) of BGB-45035(Up to approximately 14 days)
- Parts A, B, & C: Apparent systemic clearance (CL/F) of BGB-45035(Up to approximately 14 days)
- Parts A, B, & C: Apparent volume of distribution (Vz/F) of BGB-45035(Up to approximately 14 days)
- Parts B & C: Accumulation Ratios of BGB-45035(Up to approximately 14 days)
- Part E (AD Cohort E1): Change from baseline in Eczema Area and Severity Index (EASI) score at all scheduled visits(Baseline and up to 16 weeks)
- Part E (AD Cohort E1): Change from baseline in Investigator Global Assessment (IGA) scale for Atopic Dermatitis (IGA-AD) score at all scheduled visits(Baseline and up to 16 weeks)
- Part E (PN Cohort E2): Change from baseline in Investigator Global Assessment (IGA) Stage score at all scheduled visits(Baseline and up to 16 weeks)
- Part E (PN Cohort E2): Change from baseline in Investigator Global Assessment (IGA) Activity score at all scheduled visits(Baseline and up to 16 weeks)
- Part E: Change from baseline of Peak Pruritus Numerical Rating Scale (PP-NRS) at all scheduled visits(Baseline and up to 16 weeks)
- Part E: Change from baseline in Average of Pruritus Numerical Rating Scale (AP-NRS) at all scheduled visits(Baseline and up to 16 weeks)