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

Phase 1

Completed

• Conditions: Atopic Healthy Subjects; Adult Subjects with Allergic Diseases
• Interventions: Drug: Placebo; Drug: YH35324; Drug: Omalizumab

• Registration Number: NCT05564221
• Lead Sponsor: Yuhan Corporation

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2022-09-19
• Study First Submitted QC: 2022-09-29
• Study First Posted: 2022-10-03
• Study Start: 2022-11-01
• Primary Completion: 2024-11-28
• Study Completion: 2024-11-28
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	There will be 5 dose groups of YH35324, escalating from low to high doses in a stepwise manner: Cohort 1(A mg/kg) → Cohort 2(B mg/kg) → Cohorts 3(C mg/kg) and 4(C mg/kg) → Cohort 5(C mg/kg) YH35324 and placebo will be administered in a double-blinded manner.
YH35324	YH35324	There will be 5 dose groups of YH35324, escalating from low to high doses in a stepwise manner: Cohort 1(A mg/kg) → Cohort 2(B mg/kg) → Cohorts 3(C mg/kg) and 4(C mg/kg) → Cohort 5(C mg/kg) YH35324 and placebo will be administered in a double-blinded manner.
Omalizumab	Omalizumab	For Cohort 3, omalizumab 300 mg will be administered in an open-label manner.

Primary Outcome Measures

Name	Time	Method
Occurrence and severity of adverse events (AEs)	Occurrence and severity of adverse events will be observed for 141 days after administration in Cohorts 1 to 5	To evaluate the safety and tolerability following multiple administrations of YH35324

Secondary Outcome Measures

Name	Time	Method
Time to Maximum Serum Concentration (Tmax)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Apparent Serum Clearance (CL/F)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Area Under the Serum Concentration-Time Curve from Zero to the Time of the Last Quantitative Concentration (AUClast)	Serum concentrations of YH35324 will be observed for 141 days after administrationin in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Maximum Serum Concentration(Cmax)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Area Under the Serum Concentration-Time Curve during dosing interval at steady-state (AUCtau)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Serum concentrations of YH35324	Serum concentrations of YH35324 will be observed for 99 days after administration in Cohorts 5	To evaluate the PK profile of YH35324
Change in SCORing Atopic Dermatitis (SCORAD)	Change in SCORing Atopic Dermatitis (SCORAD) will be observed for 141 days after administration in Cohorts 5	To explore the clinical efficacy following multiple administrations of YH35324
Change in Pruritus-Numerical Rating Scale (NRS)	Change in Pruritus-Numerical Rating Scale (NRS) will be observed for 141 days after administration in Cohorts 5	To explore the clinical efficacy following multiple administrations of YH35324
Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Maximum Serum Concentration at steady-state (Cmax,ss)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Change in Eczema Area and Severity Index (EASI)	Change in Eczema Area and Severity Index (EASI) will be observed for 141 days after administration in Cohorts 5	To explore the clinical efficacy following multiple administrations of YH35324
Apparent Volume of Distribution (Vz/F)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Time to Maximum Serum Concentration at steady-state (Tmax,ss)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Change in serum total IgE level	Change in serum Total IgE will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PD profile on serum IgE following multiple administrations of YH35324
Accumulation ratio (Rac)	Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4	To evaluate the PK profile of YH35324
Change in serum free IgE level	Change in serum Free IgE will be observed for 141 days after administration in Cohorts 1 to 5	To evaluate the PD profile on serum IgE following multiple administrations of YH35324
Change in Validated Investigator Global Assessment (vIGA-AD)	Change in Validated Investigator Global Assessment (vIGA-AD) will be observed for 141 days after administration in Cohorts 5	To explore the clinical efficacy following multiple administrations of YH35324
Change in body surface area (BSA) of atopic dermatitis involvement	Change in body surface area (BSA) of atopic dermatitis involvement will be observed for 141 days after administration in Cohorts 5	To explore the clinical efficacy following multiple administrations of YH35324
Number of days of rescue treatment (TCS or TCI) used	Number of days of rescue treatment (TCS or TCI) used will be observed for 141 days after administration in Cohorts 5	To explore the clinical efficacy following multiple administrations of YH35324

Trial Locations

Locations (9)

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of

Nowon Eulji Medical Center; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea, Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Konkuk University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Ajou University Hospital; 🇰🇷 Suwon-si, Gyeonggi-do, Korea, Republic of

Soonchunhyang University Bucheon Hospital; 🇰🇷 Bucheon-si, Gyeonggi-do, Korea, Republic of