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

BeiGene

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: Placebo; Drug: BGB-45035

Study type: Interventional

Funder types: Industry

Identifiers

NCT06342713

CTR20243170 (Registry Identifier)

BGB-45035-101

Details and patient eligibility

About

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.

Enrollment: 195 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Parts A-D and Part F:

1. Female or male participants between the ages of 18 and 55 years inclusive (ages 18 and 45 years for Part C).
2. BMI of 18 to 32 kg/m^2; and a total body weight > 50 kg (110 lbs).
3. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
4. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
5. 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.
6. 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

1. Female or male participants between the ages of 18 to 75 years of age.

2. 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.

3. AD Cohort E1:

   1. 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.
   2. 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.

4. PN Cohort E2:

   1. 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.
   2. 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.

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.

Exclusion Criteria:

1. 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).
2. Any condition possibly affecting drug absorption (eg, gastrectomy or cholecystectomy).
3. 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.
4. 12-lead ECG demonstrating QTcF > 450 milliseconds.
5. Clinically significant abnormality on chest radiograph performed at screening or within 3 months of screening date.
6. History of tuberculosis or active or latent or inadequately treated infection, positive IGRA tests
7. Herbal supplements (including St. John's Wort) and hormone replacement therapy must be discontinued 14 days prior to the first dose of study medication.
8. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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195 participants in 7 patient groups

Part A (Single Ascending Dose)

Experimental group

Description:

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.

Treatment:

Drug: BGB-45035

Drug: Placebo

Part B (Multiple Ascending Dose)

Experimental group

Description:

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

Treatment:

Drug: BGB-45035

Drug: Placebo

Part C (Chinese Substudy)

Experimental group

Description:

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

Treatment:

Drug: BGB-45035

Drug: Placebo

Part D (Food Effect)

Experimental group

Description:

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

Treatment:

Drug: BGB-45035

Part E (AD Cohort E1)

Experimental group

Description:

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.

Treatment:

Drug: BGB-45035

Part E (PN Cohort E2)

Experimental group

Description:

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.

Treatment:

Drug: BGB-45035

Part F (Biomarker Cohort)

Experimental group

Description:

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

Treatment:

Drug: BGB-45035