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

Sponsor

Yuhan Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05564221

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

8.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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 mild allergic diseases, who have atopy.

Condition or Disease	Intervention/Treatment	Phase
Atopic Healthy Subjects Adult Subjects With Mild Allergic Diseases	Drug: YH35324 Drug: Placebo Drug: Omalizumab	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

As the YH35324 group and placebo group will be double-blinded, YH35324 and placebo will have the same appearance and packaging. Therefore, the double-blind will apply to the subjects, investigators, study coordinators, and study personnel including study pharmacists. The active control omalizumab has a different appearance and packaging from YH35324 and placebo, and will be administered in an open-label manner.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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), 2 (Q2W), 4 (Q2W), 4 (Q4W) 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), 2 (Q2W), 4 (Q2W), 4 (Q4W) 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 4, 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

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), 2 (Q2W), 4 (Q2W), 4 (Q4W) 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

Drug: Placebo

Subcutaneous injection of None of active ingredient

Active Comparator: Omalizumab

For Cohort 4, 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

Outcome Measures

Primary Outcome Measures

Occurrence and severity of adverse events (AEs) [Occurrence and severity of adverse events will be observed for 141 days after administration]
To evaluate the safety and tolerability following multiple administrations of YH35324

Secondary Outcome Measures

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 administration]
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]
To evaluate the PK profile of YH35324
Maximum Serum Concentration(Cmax) [Serum concentrations of YH35324 will be observed for 141 days after administration]
To evaluate the PK profile of YH35324
Time to Maximum Serum Concentration (Tmax) [Serum concentrations of YH35324 will be observed for 141 days after administration]
To evaluate the PK profile 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]
To evaluate the PK profile of YH35324
Apparent Serum Clearance (CL/F) [Serum concentrations of YH35324 will be observed for 141 days after administration]
To evaluate the PK profile of YH35324
Apparent Volume of Distribution (Vz/F) [Serum concentrations of YH35324 will be observed for 141 days after administration]
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]
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]
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]
To evaluate the PK profile of YH35324
Accumulation ratio (Rac) [Serum concentrations of YH35324 will be observed for 141 days after administration]
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]
To evaluate the PD profile on serum IgE following multiple administrations of YH35324
Change in serum total IgE level [Change in serum Total IgE will be observed for 141 days after administration]
To evaluate the PD profile on serum IgE following multiple administrations of YH35324

Other Outcome Measures

Changes in FcεRI expression on basophil surface [Changes in FcεRI expression will be observed for 141days after administration]
To explore the PD profile on serum basophil following multiple administrations of YH35324
Changes in allergen-induced skin prick wheal response [Changes in allergen-induced skin prick wheal response will be observed for 113 days.]
To explore inhibition on allergens (allergy antigens) following multiple administrations of YH35324
Changes in serum allergen specific IgE level [Changes in allergen-induced serum allergen specific IgE level will be observed for 141 days after administration]
To explore inhibition on allergens (allergy antigens) following multiple administrations of YH35324
Incidence of serum anti-YH35324 antibodies [Incidence of serum Anti-YH35324 antibodies will be observed for 141 Days after administration]
To explore the immunogenicity following multiple administrations of YH35324

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male or female adults aged ≥ 19 to ≤ 55 years
Serum total IgE level ≥ 30 IU/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

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	Asan Medical Center	Seoul		Korea, Republic of	05505
4	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:

NCT05564221

Other Study ID Numbers:

YH35324-102

First Posted:

Oct 3, 2022

Last Update Posted:

Nov 14, 2022

Last Verified:

Nov 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Yuhan Corporation

GI-301

YH35324

Allergic disease

Additional relevant MeSH terms:

Omalizumab

Study Results

No Results Posted as of Nov 14, 2022