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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atopic Healthy Subjects; Adult Subjects With Mild Allergic Diseases
• Intervention / Treatment: Drug: YH35324; Drug: Placebo; Drug: Omalizumab

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 mild allergic diseases, who have atopy.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: YouJin Sung; Phone Number: +82 2-828-0622; Email: yjsung@yuhan.co.kr
• Study Contact Backup: Name: Jungwook Lee; Phone Number: 02-828-0504; Email: ljw0914@yuhan.co.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16499
      • Recruiting
      • Ajou University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

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; 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; Subcutaneous injection of YH35324
Placebo Comparator: Placebo; 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; Subcutaneous injection of None of active ingredient
Active Comparator: Omalizumab; For Cohort 3, omalizumab 300 mg will be administered in an open-label manner.	Drug: Omalizumab; Subcutaneous injection of Omalizumab; Other Names: Xolair® prefilled syringe 150 for injection

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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in FcεRI expression on basophil surface	To explore the PD profile on serum basophil following multiple administrations of YH35324	Changes in FcεRI expression will be observed for 141days after administration
Changes in allergen-induced skin prick wheal response	To explore inhibition on allergens (allergy antigens) following multiple administrations of YH35324	Changes in allergen-induced skin prick wheal response will be observed for 113 days.
Changes in serum allergen specific IgE level	To explore inhibition on allergens (allergy antigens) following multiple administrations of YH35324	Changes in allergen-induced serum allergen specific IgE level will be observed for 141 days after administration
Incidence of serum anti-YH35324 antibodies	To explore the immunogenicity following multiple administrations of YH35324	Incidence of serum Anti-YH35324 antibodies will be observed for 141 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): November 1, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: September 19, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 19, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: GI-301; YH35324; Allergic disease
• Additional Relevant MeSH Terms: Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: YH35324-102

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 yhcho@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 yhcho@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