A 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 in Adults With Autoimmune Dermatological Diseases
- Conditions
- Healthy ParticipantsHealthy SubjectsHealthy VolunteersAutoimmune DiseasesHealthy Adult ParticipantsAtopic DermatitisPrurigo Nodularis
- Interventions
- Drug: Placebo
- Registration Number
- NCT06342713
- Lead Sponsor
- BeiGene
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 195
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A (Single Ascending Dose) BGB-45035 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. Part A (Single Ascending Dose) Placebo 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. Part B (Multiple Ascending Dose) BGB-45035 Part B is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy participants. Part B (Multiple Ascending Dose) Placebo Part B is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy participants. Part C (Chinese Substudy) BGB-45035 Part C is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy Chinese participants. Part C (Chinese Substudy) Placebo Part C is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy Chinese participants. Part D (Food Effect) BGB-45035 Part D is designed to assess the effect of food on BGB-45035 exposure. Part E (AD Cohort E1) BGB-45035 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. Part E (PN Cohort E2) BGB-45035 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. Part F (Biomarker Cohort) BGB-45035 Part F is designed to assess the pharmacodynamic activity of BGB-45035 in the skin of healthy volunteers.
- Primary Outcome Measures
Name Time Method Parts A-D: Number of participants with clinically significant changes from baseline in clinical laboratory values 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 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 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 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
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (13)
Innovate Clinical Research
🇦🇺Waitara, New South Wales, Australia
Cmax Clinical Research
🇦🇺Adelaide, South Australia, Australia
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Dermatology Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The Affiliated Hospital of Qingdao University Branch West Coast
🇨🇳Qingdao, Shandong, China
Chengdu Second Peoples Hospital
🇨🇳Chengdu, Sichuan, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Optimal Clinical Trials Ltd
🇳🇿Auckland, New Zealand
Pacific Clinical Research Network Auckland
🇳🇿Takapuna, New Zealand
Lakeland Clinical Trials Wellington
🇳🇿Upper Hutt, New Zealand