A Single Dose, Phase 1 Study of YH35324 in Patients With Various Allergic Diseases

Chronic Spontaneous Urticaria Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo/Active Controlled, Single Dose, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Subcutaneous Injections of YH35324 in Patients With Various Allergic Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05960708
• Other study ID #: YH35324-103
• Status: Recruiting
• Phase: Phase 1
• Start date: August 23, 2023
• Est. completion date: August 26, 2024

Study information

• Verified date: April 2024
• Source: Yuhan Corporation
• Contact: JungWook Ahn
• Phone: +82 2-828-0734
• Email: ajw8299[@]yuhan.co.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) following a single subcutaneous injection of YH35324 in subjects with various allergic diseases.

Description:

This drug(YH35324) is currently under development as a novel therapeutic agent for various IgE-mediated allergic diseases. Since YH35324 exhibits high binding affinity to human IgE, it prevents serum IgE from binding to receptors on mast cells and basophils, thereby inhibiting histamine release via degranulation following allergen exposures. In addition, YH35324 suppresses autoantibody-dependent effector cell activation by blocking anti-FcεRIα autoantibodies. This study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) following a single subcutaneous injection of YH35324 in subjects with various allergic diseases.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: August 26, 2024
• Est. primary completion date: August 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female adults aged = 19 to = 75 years [Parts 1 and 2 only]
• Diagnosis of CSU at least 6 months prior to screening
• Diagnosis of CSU inadequately controlled on 2nd-generation H1 antihistamines at the time of randomization [Part 2 only]
• Experience of inadequately uncontrolled CSU despite use of omalizumab [Part 3 only]
• Diagnosis of chronic inducible urticaria (cold urticaria) at least 3 months prior to screening
• Diagnosis of chronic inducible urticaria (cold urticaria) inadequately controlled on 2nd-generation H1 antihistamines at the time of randomization

Exclusion Criteria:

• History of malignancy within 5 years from screening
• Aspartate transaminase (AST) or alanine transaminase (ALT) level > 2 X the upper limit of normal [Parts 1 and 2 only]
• Chronic urticaria with clear etiology other than CSU [Part 3 only]
• Chronic urticaria other than studied chronic inducible urticaria (cold urticaria) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Allergic Disease
• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Cold Urticaria
• Urticaria

Intervention

Drug:
• YH35324
Subcutaneous injection of YH35324
• Omalizumab
Subcutaneous injection of Omalizumab
• Placebo
Subcutaneous injection of None of active ingredient

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang-si	Gyeonggi-do
Korea, Republic of	Dong-a University hospital	Busan
Korea, Republic of	Hallym University Dongtan Sacred Heart Hospital	Hwaseong-si	Gyeonggi-do
Korea, Republic of	CHA Bundang Medical Center	Seongnam-si	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeonggi-do

Sponsors (1)

Lead Sponsor	Collaborator
Yuhan Corporation

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximum Serum Concentration(Cmax)	To evaluate the PK profile following single administration of YH35324	Serum concentrations of YH35324 will be observed for 57 days after administration
Other	Area Under the Serum Concentration-Time Curve from Zero to the Time of the Last Quantitative Concentration (AUClast)	To evaluate the PK profile following single administration of YH35324	Serum concentrations of YH35324 will be observed for 57 days after administration
Other	Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf)	To evaluate the PK profile following single administration of YH35324	Serum concentrations of YH35324 will be observed for 57 days after administration
Other	Time to Maximum Serum Concentration (Tmax)	To evaluate the PK profile following single administration of YH35324	Serum concentrations of YH35324 will be observed for 57 days after administration
Other	Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2)	To evaluate the PK profile following single administration of YH35324	Serum concentrations of YH35324 will be observed for 57 days after administration
Other	Apparent Serum Clearance (CL/F)	To evaluate the PK profile following single administration of YH35324	Serum concentrations of YH35324 will be observed for 57 days after administration
Other	Apparent Volume of Distribution (Vz/F)	To evaluate the PK profile following single administration of YH35324	Serum concentrations of YH35324 will be observed for 57 days after administration
Other	Change in serum total IgE level	To evaluate the exploratory PD profile following single administration of YH35324	Change in serum total IgE will be observed for 57 days after administration
Other	Change in Fc?RI expression on basophil surface	To evaluate the exploratory PD profile following single administration of YH35324	Change in Fc?RI expression on basophil surface will be observed for 57 days after administration
Other	Change in serum soluble Fc?RI concentration	To evaluate the exploratory PD profile following single administration of YH35324	Change in serum soluble Fc?RI concentration will be observed for 57 days after administration
Other	Change in serum Mas-related G protein-coupled receptor-X2 (MRGPRX2) concentration	To evaluate the exploratory PD profile following single administration of YH35324	Change in serum Mas-related G protein-coupled receptor-X2 (MRGPRX2) concentration will be observed for 57 days after administration
Other	[Parts 1 and 2 only] Change in Basophil Histamine Release Assay (BHRA)	To evaluate the exploratory PD profile following single administration of YH35324	Change in Basophil Histamine Release Assay (BHRA) will be observed for 57 days after administration
Other	Change in the Urticaria Control Test (UCT) score	To explore the clinical efficacy following single administration of YH35324; * Urticaria Control Test score; minimum value: 0 / maximum value: 16; Higher scores mean a better outcome	Change in the Urticaria Control Test (UCT) score will be observed for 57 days after administration
Other	Rate of Use of rescue medications	To explore the clinical efficacy following single administration of YH35324 for using rescue medications diary	Use of rescue medications will be observed for 57 days after administration
Other	[Parts 1 and 2 only] Change in weekly Hive Severity Score 7 (HSS7)	To explore the clinical efficacy following single administration of YH35324; * Hive Severity Score 7; minimum value: 0 / maximum value: 21; Higher scores mean a worse outcome	Change in weekly Hive Severity Score 7 (HSS7) will be observed for 57 days after administration
Other	[Parts 1 and 2 only] Change in weekly Itch Severity Score 7 (ISS7)	To explore the clinical efficacy following single administration of YH35324; * Itch Severity Score 7; minimum value: 0 / maximum value: 21; Higher scores mean a worse outcome	Change in weekly Itch Severity Score 7 (ISS7) will be observed for 57 days after administration
Other	[Parts 1 and 2 only] Change in weekly Urticaria Activity Score 7 (UAS7)	To explore the clinical efficacy following single administration of YH35324; * Urticaria Activity Score 7; minimum value: 0 / maximum value: 42; Higher scores mean a worse outcome	Change in weekly Urticaria Activity Score 7 (UAS7) will be observed for 57 days after administration
Other	[Part 3 only] Change in Critical Temperature Thresholds (CTT) in response to the challenge test (TempTest® 4)	To explore the clinical efficacy following single administration of YH35324	Change in Critical Temperature Thresholds (CTT) in response to the challenge test (TempTest® 4) will be observed for 57 days after administration
Other	[Part 3 only] Change in the Peak Pruritus Numerical Rating Scale (PP-NRS) score after the challenge test (TempTest® 4)	To explore the clinical efficacy following single administration of YH35324; * Peak Pruritus Numerical Rating Scale; minimum value: 0 / maximum value: 10; Higher scores mean a worse outcome	Change in the Peak Pruritus Numerical Rating Scale (PP-NRS) score after the challenge test (TempTest® 4) will be observed for 57 days after administration
Other	Incidence of serum anti-YH35324 antibodies	To explore the immunogenicity following single administration of YH35324	Incidence of serum anti-YH35324 antibodies will be observed for 57 days after administration
Primary	Occurrence and severity of adverse events (AEs)	To evaluate the safety and tolerability following single administration of YH35324	Occurrence and severity of adverse events will be observed for 57 days after administration
Secondary	Change in serum free IgE level	To evaluate the PD profile on serum IgE following single administration of YH35324	Change in serum free IgE will be observed for 57 days after administration