Adult Subjects With Allergic Diseases, Atopic Healthy Subjects
Conditions
Keywords
GI-301, YH35324, Allergic disease
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 allergic diseases, who have atopy.
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 allergic diseases, who have atopy.
Interventions
DRUGYH35324
Subcutaneous injection of YH35324
DRUGPlacebo
Subcutaneous injection of None of active ingredient
DRUGOmalizumab
Subcutaneous injection of Omalizumab
Sponsors
Yuhan Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female adults aged ≥ 19 to ≤ 55 years(Cohort 5, Mald or female adults ≥ 19) * Serum total IgE level ≥ 30 IU/mL or 30 to 700 IU/mL or \>700IU/mL(Not Applicable for Cohort 5) * Meeting the following cohort-specific disease severity criteria \[Cohorts 1-4\]: 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) \[Cohort 5\]: Subject who have been diagnosed with moderate to severe atopic dermatitis
Exclusion criteria
* History of malignancy * Positive drug screen result * 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(For Cohort 5, within 12 months prior to randomization) * History of participation in another clinical trial within 6 months prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence and severity of adverse events (AEs) | Occurrence and severity of adverse events will be observed for 141 days after administration in Cohorts 1 to 5 | To evaluate the safety and tolerability following multiple administrations of YH35324 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 in Cohorts 1 to 4 | To evaluate the PK profile of YH35324 |
| Change in Eczema Area and Severity Index (EASI) | Change in Eczema Area and Severity Index (EASI) will be observed for 141 days after administration in Cohorts 5 | To explore the clinical efficacy following multiple administrations of YH35324 |
| Change in Validated Investigator Global Assessment (vIGA-AD) | Change in Validated Investigator Global Assessment (vIGA-AD) will be observed for 141 days after administration in Cohorts 5 | To explore the clinical efficacy following multiple administrations of YH35324 |
| Change in SCORing Atopic Dermatitis (SCORAD) | Change in SCORing Atopic Dermatitis (SCORAD) will be observed for 141 days after administration in Cohorts 5 | To explore the clinical efficacy following multiple administrations of YH35324 |
| Change in Pruritus-Numerical Rating Scale (NRS) | Change in Pruritus-Numerical Rating Scale (NRS) will be observed for 141 days after administration in Cohorts 5 | To explore the clinical efficacy following multiple administrations of YH35324 |
| Change in body surface area (BSA) of atopic dermatitis involvement | Change in body surface area (BSA) of atopic dermatitis involvement will be observed for 141 days after administration in Cohorts 5 | To explore the clinical efficacy following multiple administrations of YH35324 |
| Number of days of rescue treatment (TCS or TCI) used | Number of days of rescue treatment (TCS or TCI) used will be observed for 141 days after administration in Cohorts 5 | To explore the clinical efficacy following multiple administrations of YH35324 |
| 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 administrationin in Cohorts 1 to 4 | 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 in Cohorts 1 to 4 | To evaluate the PK profile of YH35324 |
| Maximum Serum Concentration(Cmax) | Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4 | 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 in Cohorts 1 to 4 | 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 in Cohorts 1 to 4 | To evaluate the PK profile of YH35324 |
| Apparent Serum Clearance (CL/F) | Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4 | 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 in Cohorts 1 to 4 | 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 in Cohorts 1 to 4 | 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 in Cohorts 1 to 4 | To evaluate the PK profile of YH35324 |
| Accumulation ratio (Rac) | Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4 | 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 in Cohorts 1 to 5 | 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 in Cohorts 1 to 4 | To evaluate the PD profile on serum IgE following multiple administrations of YH35324 |
| Serum concentrations of YH35324 | Serum concentrations of YH35324 will be observed for 99 days after administration in Cohorts 5 | To evaluate the PK profile of YH35324 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in serum allergen specific IgE level | Changes in allergen-induced serum allergen specific IgE level will be observed for 141 days after administration in Cohorts 1 to 5 | 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 in Cohorts 1 to 5 | To explore the immunogenicity following multiple administrations of YH35324 |
| Changes in serum Thymus and Activation-Regulated Chemokine (TARC, CCL17) and Macrophage-Derived Chemokine (MDC, CCL22) | Changes in serum Thymus and Activation-Regulated Chemokine and Macrophage-Derived Chemokine will be observed for 141 Days after administration in Cohorts 5 | To explore the PD following multiple administrations of YH35324 |
| Changes in serum cytokines (IL-4, IL-5, IL-10, IL-18, IL-22, IL-13, IL-31, IL-33, and IFN-γ) levels | Changes in serum cytokines levels will be observed for 141 Days after administration in Cohorts 5 | To explore the PD 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 in Cohorts 1 to 5 | To explore inhibition on allergens (allergy antigens) following multiple administrations of YH35324 |
| Changes in FcεRI expression on basophil surface | Changes in FcεRI expression will be observed for 141days after administrationin in Cohorts 1 to 4 | To explore the PD profile on serum basophil following multiple administrations of YH35324 |
Countries
South Korea
Outcome results
None listed