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

• Sponsor: Yuhan Corporation (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05960708
• Collaborator: (none)
• Enrollment: 36
• Locations: 5
• Arms: 3
• Anticipated Duration (Months): 6.4
• Patients Per Site: 7.2
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Allergic Disease; Chronic Spontaneous Urticaria; Chronic Inducible Urticaria; Cold Urticaria	Drug: YH35324; Drug: Omalizumab; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Each IP will be labeled with a unique IP number, and the number will be associated with the randomized treatment group. Interactive Web Response System (IWRS) will be used to assign a randomization number and IP number. As YH35324, placebo, and omalizumab differ in appearance, the assigned treatment group of subjects should be disclosed to study pharmacists and unblinded staff who prepare (taking an appropriate and correct amount (mL) of the IP based on the subject's body weight into a syringe), dispense, and administer the IPs, in order to maintain the blind. Therefore, the treatment group information of subjects will be checked through IWRS with limited access before administration of the IP, and only study pharmacists and unblinded staff are allowed to access the system. The study pharmacists and unblinded staff should not disclose the assigned treatment group of enrolled subjects to the principal investigator or study staff.
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Aug 30, 2023
• Anticipated Primary Completion Date: Mar 13, 2024
• Anticipated Study Completion Date: Mar 13, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: YH35324 [Part 1] A total of 18 subjects will be randomized in a 1:1:1 ratio to the YH35324 3 mg/kg, YH35324 6 mg/kg, or omalizumab group. [Part 2] A total of 9 subjects will be randomized in a 2:1 ratio to the YH35324 6 mg/kg or placebo group. [Part 3] A total of 9 subjects will be randomized in a 2:1 ratio to the YH35324 6 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 3 mg/kg, YH35324 6 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 6 mg/kg or placebo group. [Part 3] A total of 9 subjects will be randomized in a 2:1 ratio to the YH35324 6 mg/kg or placebo group.	Drug: Placebo; Subcutaneous injection of None of active ingredient

Outcome Measures

Primary Outcome Measures

1. Occurrence and severity of adverse events (AEs) [Occurrence and severity of adverse events will be observed for 57 days after administration]

   To evaluate the safety and tolerability following single administration of YH35324

Secondary Outcome Measures

1. Change in serum free IgE level [Change in serum free IgE will be observed for 57 days after administration]

   To evaluate the PD profile on serum IgE following single administration of YH35324

Other Outcome Measures

1. Maximum Serum Concentration(Cmax) [Serum concentrations of YH35324 will be observed for 57 days after administration]

   To evaluate the PK profile following single administration of YH35324

2. 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 57 days after administration]

   To evaluate the PK profile following single administration of YH35324

3. Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf) [Serum concentrations of YH35324 will be observed for 57 days after administration]

   To evaluate the PK profile following single administration of YH35324

4. Time to Maximum Serum Concentration (Tmax) [Serum concentrations of YH35324 will be observed for 57 days after administration]

   To evaluate the PK profile following single administration of YH35324

5. Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2) [Serum concentrations of YH35324 will be observed for 57 days after administration]

   To evaluate the PK profile following single administration of YH35324

6. Apparent Serum Clearance (CL/F) [Serum concentrations of YH35324 will be observed for 57 days after administration]

   To evaluate the PK profile following single administration of YH35324

7. Apparent Volume of Distribution (Vz/F) [Serum concentrations of YH35324 will be observed for 57 days after administration]

   To evaluate the PK profile following single administration of YH35324

8. Change in serum total IgE level [Change in serum total IgE will be observed for 57 days after administration]

   To evaluate the exploratory PD profile following single administration of YH35324

9. Change in FcƐRI expression on basophil surface [Change in FcƐRI expression on basophil surface will be observed for 57 days after administration]

   To evaluate the exploratory PD profile following single administration of YH35324

10. Change in serum soluble FcƐRI concentration [Change in serum soluble FcƐRI concentration will be observed for 57 days after administration]

    To evaluate the exploratory PD profile following single administration of YH35324

11. Change in serum Mas-related G protein-coupled receptor-X2 (MRGPRX2) concentration [Change in serum Mas-related G protein-coupled receptor-X2 (MRGPRX2) concentration will be observed for 57 days after administration]

    To evaluate the exploratory PD profile following single administration of YH35324

12. [Parts 1 and 2 only] Change in Basophil Histamine Release Assay (BHRA) [Change in Basophil Histamine Release Assay (BHRA) will be observed for 57 days after administration]

    To evaluate the exploratory PD profile following single administration of YH35324

13. Change in the Urticaria Control Test (UCT) score [Change in the Urticaria Control Test (UCT) score will be observed for 57 days after administration]

    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

14. Rate of Use of rescue medications [Use of rescue medications will be observed for 57 days after administration]

    To explore the clinical efficacy following single administration of YH35324 for using rescue medications diary

15. [Parts 1 and 2 only] Change in weekly Hive Severity Score 7 (HSS7) [Change in weekly Hive Severity Score 7 (HSS7) will be observed for 57 days after administration]

    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

16. [Parts 1 and 2 only] Change in weekly Itch Severity Score 7 (ISS7) [Change in weekly Itch Severity Score 7 (ISS7) will be observed for 57 days after administration]

    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

17. [Parts 1 and 2 only] Change in weekly Urticaria Activity Score 7 (UAS7) [Change in weekly Urticaria Activity Score 7 (UAS7) will be observed for 57 days after administration]

    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

18. [Part 3 only] Change in Critical Temperature Thresholds (CTT) in response to the challenge test (TempTest® 4) [Change in Critical Temperature Thresholds (CTT) in response to the challenge test (TempTest® 4) will be observed for 57 days after administration]

    To explore the clinical efficacy following single administration of YH35324

19. [Part 3 only] Change in the Peak Pruritus Numerical Rating Scale (PP-NRS) score after the challenge test (TempTest® 4) [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]

    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

20. Incidence of serum anti-YH35324 antibodies [Incidence of serum anti-YH35324 antibodies will be observed for 57 days after administration]

    To explore the immunogenicity following single administration of YH35324

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
2	Ajou University Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of	16499
3	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
4	Asan Medical Center	Seoul		Korea, Republic of	05505
5	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591

Sponsors and Collaborators

• Yuhan Corporation

Investigators

• Study Chair: Hae-Sim Park, Ajou University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yuhan Corporation
• ClinicalTrials.gov Identifier: NCT05960708
• Other Study ID Numbers: YH35324-103
• First Posted: Jul 27, 2023
• Last Update Posted: Jul 27, 2023
• Last Verified: Jul 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Yuhan Corporation: GI-301; YH35324; Allergic disease; CSU; CINDU; Cold urticaria
• Additional relevant MeSH terms: Urticaria; Chronic Urticaria; Chronic Inducible Urticaria; Omalizumab

Study Results

No Results Posted as of Jul 27, 2023