Allergic Disease, Chronic Inducible Urticaria, Chronic Spontaneous Urticaria, Cold Urticaria
Conditions
Keywords
GI-301, YH35324, Allergic disease, CSU, CINDU, Cold urticaria
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.
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.
Interventions
DRUGYH35324
Subcutaneous injection of YH35324
DRUGOmalizumab
Subcutaneous injection of Omalizumab
DRUGPlacebo
Subcutaneous injection of None of active ingredient
Sponsors
Yuhan Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female adults aged ≥ 19 to ≤ 75 years \[Parts 1 and 2 only\] * Diagnosis of CSU \[Part 2 only\] * Experience of inadequately uncontrolled CSU despite use of omalizumab \[Part 3 only\] * Diagnosis of chronic inducible urticaria (cold urticaria)
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 potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| [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 |
| [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 |
| [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 |
| [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 |
| [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 |
| 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 |
| [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 |
| 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 |
Countries
South Korea
Outcome results
None listed