Clinical trial NCT05564221: A Multiple Ascending Dose, Phase 1b Study of YH35324 in Atopic Healthy Subjects or Subjects With Allergic Diseases
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 Allergic Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Healthy Subjects
Adult Subjects With Allergic Diseases
Keywords: GI-301
YH35324
Allergic disease
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2022-10-03
Enrollment: 46
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence and severity of adverse events (AEs)
timeFrame: Occurrence and severity of adverse events will be observed for 141 days after administration in Cohorts 1 to 5
Secondary outcomes:
measure: Area Under the Serum Concentration-Time Curve from Zero to the Time of the Last Quantitative Concentration (AUClast)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administrationin in Cohorts 1 to 4
measure: Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Maximum Serum Concentration(Cmax)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Time to Maximum Serum Concentration (Tmax)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Apparent Serum Clearance (CL/F)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Area Under the Serum Concentration-Time Curve during dosing interval at steady-state (AUCtau)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Maximum Serum Concentration at steady-state (Cmax,ss)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Time to Maximum Serum Concentration at steady-state (Tmax,ss)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Accumulation ratio (Rac)
timeFrame: Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4
measure: Change in serum free IgE level
timeFrame: Change in serum Free IgE will be observed for 141 days after administration in Cohorts 1 to 5
measure: Change in serum total IgE level
timeFrame: Change in serum Total IgE will be observed for 141 days after administration in Cohorts 1 to 4
measure: Serum concentrations of YH35324
timeFrame: Serum concentrations of YH35324 will be observed for 99 days after administration in Cohorts 5
measure: Change in Eczema Area and Severity Index (EASI)
timeFrame: Change in Eczema Area and Severity Index (EASI) will be observed for 141 days after administration in Cohorts 5
measure: Change in Validated Investigator Global Assessment (vIGA-AD)
timeFrame: Change in Validated Investigator Global Assessment (vIGA-AD) will be observed for 141 days after administration in Cohorts 5
measure: Change in SCORing Atopic Dermatitis (SCORAD)
timeFrame: Change in SCORing Atopic Dermatitis (SCORAD) will be observed for 141 days after administration in Cohorts 5
measure: Change in Pruritus-Numerical Rating Scale (NRS)
timeFrame: Change in Pruritus-Numerical Rating Scale (NRS) will be observed for 141 days after administration in Cohorts 5
measure: Change in body surface area (BSA) of atopic dermatitis involvement
timeFrame: Change in body surface area (BSA) of atopic dermatitis involvement will be observed for 141 days after administration in Cohorts 5
measure: Number of days of rescue treatment (TCS or TCI) used
timeFrame: Number of days of rescue treatment (TCS or TCI) used will be observed for 141 days after administration in Cohorts 5
Other outcomes:
measure: Changes in FcεRI expression on basophil surface
timeFrame: Changes in FcεRI expression will be observed for 141days after administrationin in Cohorts 1 to 4
measure: Changes in allergen-induced skin prick wheal response
timeFrame: Changes in allergen-induced skin prick wheal response will be observed for 113 days in Cohorts 1 to 5
measure: Changes in serum allergen specific IgE level
timeFrame: Changes in allergen-induced serum allergen specific IgE level will be observed for 141 days after administration in Cohorts 1 to 5
measure: Incidence of serum anti-YH35324 antibodies
timeFrame: Incidence of serum Anti-YH35324 antibodies will be observed for 141 Days after administration in Cohorts 1 to 5
measure: Changes in serum Thymus and Activation-Regulated Chemokine (TARC, CCL17) and Macrophage-Derived Chemokine (MDC, CCL22)
timeFrame: Changes in serum Thymus and Activation-Regulated Chemokine and Macrophage-Derived Chemokine will be observed for 141 Days after administration in Cohorts 5
measure: Changes in serum cytokines (IL-4, IL-5, IL-10, IL-18, IL-22, IL-13, IL-31, IL-33, and IFN-γ) levels
timeFrame: Changes in serum cytokines levels will be observed for 141 Days after administration in Cohorts 5
Locations:
city: Bucheon-si
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Nowon Eulji Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
Study officials:
affiliation: Ajou University School of Medicine
name: Hae-Sim Park
role: STUDY_CHAIR
References: