A Multiple Ascending Dose, Phase 1b Study of YH35324 in Atopic Healthy Subjects or Subjects With Allergic Diseases

Yuhan Corporation46 enrolled

Overview

This study aims to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles following multiple subcutaneous injections of YH35324 in healthy subjects or subjects with allergic diseases, who have atopy.

YH35324 is a drug under development as a novel therapeutic agent for various IgE-mediated allergic diseases. Since YH35324 has a high binding affinity to human IgE, it prevents serum IgE from binding to receptors on mast cells and basophil, thereby inhibiting histamine release caused by degranulation when exposed to allergens. This study aims to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles following multiple subcutaneous injections of YH35324 in healthy subjects or subjects with allergic diseases, who have atopy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Atopic Healthy Subjects Adult Subjects With Allergic Diseases

Interventions

YH35324DRUG

Subcutaneous injection of YH35324

PlaceboDRUG

Subcutaneous injection of None of active ingredient

OmalizumabDRUG

Subcutaneous injection of Omalizumab

Eligibility

Sex: ALLMin age: 19 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female adults aged ≥ 19 to ≤ 55 years(Cohort 5, Mald or female adults ≥ 19) * Serum total IgE level ≥ 30 IU/mL or 30 to 700 IU/mL or \>700IU/mL(Not Applicable for Cohort 5) * Meeting the following cohort-specific disease severity criteria \[Cohorts 1-4\]: Healthy subjects without any pathological symptoms or findings from medical examination, or subjects with a history of mild allergic diseases (allergic rhinitis, atopic dermatitis, food allergy, urticaria, or allergic asthma) \[Cohort 5\]: Subject who have been diagnosed with moderate to severe atopic dermatitis Exclusion Criteria: * History of malignancy * Positive drug screen result * transaminase (AST) or alanine transaminase (ALT) level \> 2 X the upper limit of normal * Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula * Allergy immunotherapy initiated or changed within 6 months prior to randomization(For Cohort 5, within 12 months prior to randomization) * History of participation in another clinical trial within 6 months prior to randomization

Locations (9)

Soonchunhyang University Bucheon Hospital

Bucheon-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Nowon Eulji Medical Center

Outcomes

Primary Outcomes

Occurrence and severity of adverse events (AEs)

To evaluate the safety and tolerability following multiple administrations of YH35324

Time frame: Occurrence and severity of adverse events will be observed for 141 days after administration in Cohorts 1 to 5

Secondary Outcomes

Area Under the Serum Concentration-Time Curve from Zero to the Time of the Last Quantitative Concentration (AUClast)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administrationin in Cohorts 1 to 4

Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Maximum Serum Concentration(Cmax)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Time to Maximum Serum Concentration (Tmax)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Apparent Serum Clearance (CL/F)

Data from ClinicalTrials.gov

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Korea University Anam Hospital

Seoul, South Korea

Severance Hospital

Seoul, South Korea

Konkuk University Medical Center

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Apparent Volume of Distribution (Vz/F)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Area Under the Serum Concentration-Time Curve during dosing interval at steady-state (AUCtau)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Maximum Serum Concentration at steady-state (Cmax,ss)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Time to Maximum Serum Concentration at steady-state (Tmax,ss)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Accumulation ratio (Rac)

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4

Change in serum free IgE level

To evaluate the PD profile on serum IgE following multiple administrations of YH35324

Time frame: Change in serum Free IgE will be observed for 141 days after administration in Cohorts 1 to 5

Change in serum total IgE level

To evaluate the PD profile on serum IgE following multiple administrations of YH35324

Time frame: Change in serum Total IgE will be observed for 141 days after administration in Cohorts 1 to 4

Serum concentrations of YH35324

To evaluate the PK profile of YH35324

Time frame: Serum concentrations of YH35324 will be observed for 99 days after administration in Cohorts 5

Change in Eczema Area and Severity Index (EASI)

To explore the clinical efficacy following multiple administrations of YH35324

Time frame: Change in Eczema Area and Severity Index (EASI) will be observed for 141 days after administration in Cohorts 5

Change in Validated Investigator Global Assessment (vIGA-AD)

To explore the clinical efficacy following multiple administrations of YH35324

Time frame: Change in Validated Investigator Global Assessment (vIGA-AD) will be observed for 141 days after administration in Cohorts 5

Change in SCORing Atopic Dermatitis (SCORAD)

To explore the clinical efficacy following multiple administrations of YH35324

Time frame: Change in SCORing Atopic Dermatitis (SCORAD) will be observed for 141 days after administration in Cohorts 5

Change in Pruritus-Numerical Rating Scale (NRS)

To explore the clinical efficacy following multiple administrations of YH35324

Time frame: Change in Pruritus-Numerical Rating Scale (NRS) will be observed for 141 days after administration in Cohorts 5

Change in body surface area (BSA) of atopic dermatitis involvement

To explore the clinical efficacy following multiple administrations of YH35324

Time frame: Change in body surface area (BSA) of atopic dermatitis involvement will be observed for 141 days after administration in Cohorts 5

Number of days of rescue treatment (TCS or TCI) used

To explore the clinical efficacy following multiple administrations of YH35324

Time frame: Number of days of rescue treatment (TCS or TCI) used will be observed for 141 days after administration in Cohorts 5