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

Study Overview
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Brief Summary
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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 mild allergic diseases, who have atopy.

Detailed Description
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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 mild allergic diseases, who have atopy.

Official Title
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A Randomized, Double-Blind, Placebo/Active Controlled, Multiple Ascending Dose, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Subcutaneous Injections of YH35324 in Atopic Healthy Subjects or Subjects With Mild Allergic Diseases

Conditions
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Atopic Healthy Subjects, Adult Subjects With Mild Allergic Diseases

Intervention / Treatment
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* Drug: YH35324
* Drug: Placebo
* Drug: Omalizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults aged ≥ 19 to ≤ 55 years Serum total IgE level ≥ 30 IU/mL or 30 to 700 IU/mL or >700IU/mL 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) Exclusion Criteria: History of malignancy Positive drug screen result Aspartate 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 History of participation in another clinical trial within 6 months prior to randomization

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YH35324<br>There will be 4 dose groups of YH35324, escalating from low to high doses in a stepwise manner: 0.75 (Q2W), 3 (Q4W), 6 (Q4W), 6 (Q8W) mg/kg (Cohort 1 → Cohort 2, Cohort 2 → Cohorts 3 and 4). YH35324 and placebo will be administered in a double-blinded manner. | Drug: YH35324<br>* Subcutaneous injection of YH35324<br>|
| Placebo Comparator: Placebo<br>There will be 4 dose groups of YH35324, escalating from low to high doses in a stepwise manner: 0.75 (Q2W), 3 (Q4W), 6 (Q4W), 6 (Q8W) mg/kg (Cohort 1 → Cohort 2, Cohort 2 → Cohorts 3 and 4). YH35324 and placebo will be administered in a double-blinded manner. | Drug: Placebo<br>* Subcutaneous injection of None of active ingredient<br>|
| Active Comparator: Omalizumab<br>For Cohort 3, omalizumab 300 mg will be administered in an open-label manner. | Drug: Omalizumab<br>* Subcutaneous injection of Omalizumab<br>* Other names: Xolair® prefilled syringe 150 for injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence and severity of adverse events (AEs) | To evaluate the safety and tolerability following multiple administrations of YH35324 | Occurrence and severity of adverse events will be observed for 141 days after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Maximum Serum Concentration(Cmax) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Time to Maximum Serum Concentration (Tmax) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Apparent Serum Clearance (CL/F) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Apparent Volume of Distribution (Vz/F) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Area Under the Serum Concentration-Time Curve during dosing interval at steady-state (AUCtau) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Maximum Serum Concentration at steady-state (Cmax,ss) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Time to Maximum Serum Concentration at steady-state (Tmax,ss) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Accumulation ratio (Rac) | To evaluate the PK profile of YH35324 | Serum concentrations of YH35324 will be observed for 141 days after administration | 
| Change in serum free IgE level | To evaluate the PD profile on serum IgE following multiple administrations of YH35324 | Change in serum Free IgE will be observed for 141 days after administration | 
| Change in serum total IgE level | To evaluate the PD profile on serum IgE following multiple administrations of YH35324 | Change in serum Total IgE will be observed for 141 days after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GI-301, YH35324, Allergic disease