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

NCT06342713 | Recruiting Phase 1 DMC

• 2 other identifiers: BGB-45035-101CTR20243170
• Study Type: interventional
• Target: 211
• Locations: 3 countries
• Sites: 13

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.

Conditions

Healthy Participants; Healthy Subjects; Healthy Volunteers; Autoimmune Diseases; Healthy Adult Participants; Atopic Dermatitis; Prurigo Nodularis

Keywords

Healthy Volunteers; Healthy Subjects; Healthy Participants; BGB-45035; Healthy Adult Participants; IL-33-induced skin inflammation; atopic dermatitis; prurigo nodularis; IRAK4; CDAC

Outcome Measures

Primary Outcomes (4)

• 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

• Parts A-D: Number of participants with clinically significant changes from baseline in clinical laboratory values

  Laboratory values include hematology, clinical chemistry, coagulation, and urinalysis

  Baseline and up to approximately 1 month

• Parts A-D: Number of participants with clinically significant changes from baseline in vital signs

  Vital signs include blood pressure and pulse rate

  Baseline and up to approximately 1 month

• Parts A-D: Number of participants with clinically significant changes from baseline in cardiac conduction intervals

  As assessed via 12-lead electrocardiogram (ECG)

  Baseline and up to approximately 1 month

Secondary Outcomes (16)

• 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

Study Arms (7)

Part A (Single Ascending Dose)

EXPERIMENTAL

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.

Drug: BGB-45035; Drug: Placebo

Part B (Multiple Ascending Dose)

EXPERIMENTAL

Part B is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy participants.

Drug: BGB-45035; Drug: Placebo

Part C (Chinese Substudy)

EXPERIMENTAL

Part C is designed to assess safety, tolerability, PK, and pharmacodynamic profile after repeated dosing of BGB-45035 in healthy Chinese participants.

Drug: BGB-45035; Drug: Placebo

Part D (Food Effect)

EXPERIMENTAL

Part D is designed to assess the effect of food on BGB-45035 exposure.

Drug: BGB-45035

Part E (AD Cohort E1)

EXPERIMENTAL

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.

Drug: BGB-45035

Part E (PN Cohort E2)

EXPERIMENTAL

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.

Drug: BGB-45035

Part F (Biomarker Cohort)

EXPERIMENTAL

Part F is designed to assess the pharmacodynamic activity of BGB-45035 in the skin of healthy volunteers.

Drug: BGB-45035

Interventions

BGB-45035 DRUG

Administered orally

Part A (Single Ascending Dose); Part B (Multiple Ascending Dose); Part C (Chinese Substudy); Part D (Food Effect); Part E (AD Cohort E1); Part E (PN Cohort E2); Part F (Biomarker Cohort)

Placebo DRUG

Administered orally

Part A (Single Ascending Dose); Part B (Multiple Ascending Dose); Part C (Chinese Substudy)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (13)

Innovate Clinical Research

Waitara, New South Wales, NSW 2077, Australia

RECRUITING

Cmax Clinical Research

Adelaide, South Australia, SA 5000, Australia

ACTIVE NOT RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, 100000, China

COMPLETED

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 630014, China

ACTIVE NOT RECRUITING

Dermatology Hospital of Southern Medical University

Guangzhou, Guangdong, China

COMPLETED

Xiangya Hospital of Central South University

Changsha, Hunan, 410008, China

COMPLETED

Suzhou Municipal Hospital

Suzhou, Jiangsu, 215002, China

COMPLETED

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

COMPLETED

The Affiliated Hospital of Qingdao University Branch West Coast

Qingdao, Shandong, 266555, China

ACTIVE NOT RECRUITING

Chengdu Second Peoples Hospital

Chengdu, Sichuan, 610021, China

COMPLETED

Optimal Clinical Trials Ltd

Auckland, 1010, New Zealand

RECRUITING

Pacific Clinical Research Network Auckland

Takapuna, 0622, New Zealand

RECRUITING

Lakeland Clinical Trials Wellington

Upper Hutt, 5018, New Zealand

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases; Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Immune System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Central Study Contacts

BeiGene

CONTACT

1-877-828-5568; ClinicalTrials@beigene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The cohorts in Part A, B, and C will be double-blinded, while Parts D, E, and F will be open-label.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: April 2, 2024
• Study Start: June 20, 2024
• Primary Completion (Estimated): May 23, 2026
• Study Completion (Estimated): May 23, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

AU (2); CN (8); NZ (3)