Clinical trial NCT06342713: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-04-02
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs) in Parts A-E
timeFrame: 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
measure: Parts A-D: Number of participants with clinically significant changes from baseline in clinical laboratory values
timeFrame: Baseline and up to approximately 1 month
measure: Parts A-D: Number of participants with clinically significant changes from baseline in vital signs
timeFrame: Baseline and up to approximately 1 month
measure: Parts A-D: Number of participants with clinically significant changes from baseline in cardiac conduction intervals
timeFrame: Baseline and up to approximately 1 month
Secondary outcomes:
measure: Parts A & D: Area under the plasma concentration time curve from time zero to last quantifiable time (AUClast) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts A & D: Area under the plasma concentration time curve from time zero to infinite time (AUCinf) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts B & C: Area under the plasma concentration time curve from time zero to end of dosing interval (AUCtau) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts A, B, C & D: Maximum observed plasma concentration (Cmax) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts A, B, C & D: Time to maximum plasma concentration (Tmax) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts B & C: Trough plasma concentration (Ctrough) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts A, B, C & D: Half life (t½) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts A, B, & C: Apparent systemic clearance (CL/F) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts A, B, & C: Apparent volume of distribution (Vz/F) of BGB-45035
timeFrame: Up to approximately 14 days
measure: Parts B & C: Accumulation Ratios of BGB-45035
timeFrame: Up to approximately 14 days
measure: Part E (AD Cohort E1): Change from baseline in Eczema Area and Severity Index (EASI) score at all scheduled visits
timeFrame: Baseline and up to 16 weeks
measure: Part E (AD Cohort E1): Change from baseline in Investigator Global Assessment (IGA) scale for Atopic Dermatitis (IGA-AD) score at all scheduled visits
timeFrame: Baseline and up to 16 weeks
measure: Part E (PN Cohort E2): Change from baseline in Investigator Global Assessment (IGA) Stage score at all scheduled visits
timeFrame: Baseline and up to 16 weeks
measure: Part E (PN Cohort E2): Change from baseline in Investigator Global Assessment (IGA) Activity score at all scheduled visits
timeFrame: Baseline and up to 16 weeks
measure: Part E: Change from baseline of Peak Pruritus Numerical Rating Scale (PP-NRS) at all scheduled visits
timeFrame: Baseline and up to 16 weeks
measure: Part E: Change from baseline in Average of Pruritus Numerical Rating Scale (AP-NRS) at all scheduled visits
timeFrame: Baseline and up to 16 weeks
Other outcomes:
Locations:
city: Waitara
country: Australia
facility: Innovate Clinical Research
state: New South Wales
city: Adelaide
country: Australia
facility: Cmax Clinical Research
state: South Australia
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Dermatology Hospital of Southern Medical University
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University Branch West Coast
state: Shandong
city: Chengdu
country: China
facility: Chengdu Second Peoples Hospital
state: Sichuan
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials Ltd
city: Takapuna
country: New Zealand
facility: Pacific Clinical Research Network Auckland
city: Upper Hutt
country: New Zealand
facility: Lakeland Clinical Trials Wellington
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: