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

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

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.

Study Overview

• Status: Completed
• Conditions: Allergic Disease; Chronic Spontaneous Urticaria; Cold Urticaria; Chronic Inducible Urticaria
• Intervention / Treatment: Drug: YH35324; Drug: Placebo; Drug: Omalizumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, Korea, Republic of, 14068
      • Hallym University Sacred Heart Hospital
    • Hwaseong-si, Gyeonggi-do, Korea, Republic of, 18450
      • Hallym University Dongtan Sacred Heart Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
      • CHA Bundang Medical Center
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16499
      • Ajou University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female adults aged ≥ 19 to ≤ 75 years

[Parts 1 and 2 only]

• Diagnosis of CSU

[Part 2 only]

• Experience of inadequately uncontrolled CSU despite use of omalizumab

[Part 3 only]

• Diagnosis of chronic inducible urticaria (cold urticaria)

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 potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YH35324; [Part 1] A total of 18 subjects will be randomized in a 1:1:1 ratio to the YH35324 A mg/kg, YH35324 B mg/kg, or omalizumab group. [Part 2] A total of 9 subjects will be randomized in a 2:1 ratio to the YH35324 B mg/kg or placebo group. [Part 3] A total of 9 subjects will be randomized in a 2:1 ratio to the YH35324 B mg/kg or placebo group.	Drug: YH35324; Subcutaneous injection of YH35324
Active Comparator: Omalizumab; [Part 1] A total of 18 subjects will be randomized in a 1:1:1 ratio to the YH35324 A mg/kg, YH35324 B mg/kg, or omalizumab group.	Drug: Omalizumab; Subcutaneous injection of Omalizumab; Other Names: Xolair® prefilled syringe 150 for injection
Placebo Comparator: Placebo; [Part 2] A total of 9 subjects will be randomized in a 2:1 ratio to the YH35324 B mg/kg or placebo group. [Part 3] A total of 9 subjects will be randomized in a 2:1 ratio to the YH35324 B mg/kg or placebo group.	Drug: Placebo; Subcutaneous injection of None of active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
Change in FcƐRI expression on basophil surface	To evaluate the exploratory PD profile following single administration of YH35324	Change in FcƐRI expression on basophil surface will be observed for 57 days after administration
Change in serum soluble FcƐRI concentration	To evaluate the exploratory PD profile following single administration of YH35324	Change in serum soluble FcƐRI concentration will be observed for 57 days after administration
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
[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
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
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
[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
[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
[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
[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
[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
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

Collaborators and Investigators

• Sponsor: Yuhan Corporation
• Investigators: Study Chair: Hae-Sim Park, Ajou University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2023
• Primary Completion (Actual): September 13, 2024
• Study Completion (Actual): September 13, 2024

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 21, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: CINDU; CSU; GI-301; YH35324; Allergic disease; Cold urticaria
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Vascular; Chronic Urticaria; Chronic Inducible Urticaria; Cold Urticaria; Urticaria; Respiratory System Agents; Anti-Asthmatic Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: YH35324-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data (including data dictionaries) that underline the results reported in study-related publications will be made available during the period beginning 1 year and ending 5 years after all trial primary and secondary endpoints were assessed. Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to yjshim@yuhan.co.kr

A summary of the study results will be posted in the publicly accessible database (i.e. clinicaltrials.gov) no later than 1 year after the study's primary completion date.

• IPD Sharing Time Frame: Beginning 1 year and ending 5 years after all trial endpoints were assessed
• IPD Sharing Access Criteria: Only requests from researchers who provide a methodologically sound proposal will be reviewed and approved by the sponsor. The analysis type should be in accordance with aims in the proposal approved by the sponsor. Proposals should be directed to yjshim@yuhan.co.kr
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No