Clinical trial NCT05960708: A Single Dose, Phase 1 Study of YH35324 in Patients with Various Allergic Diseases
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Allergic Disease
Chronic Spontaneous Urticaria
Chronic Inducible Urticaria
Cold Urticaria
Keywords: GI-301
YH35324
Allergic disease
CSU
CINDU
Cold urticaria
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 \&amp;gt; 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.

Primary outcomes:
measure: Occurrence and severity of adverse events (AEs)
timeFrame: Occurrence and severity of adverse events will be observed for 57 days after administration
Secondary outcomes:
measure: Change in serum free IgE level
timeFrame: Change in serum free IgE will be observed for 57 days after administration
Other outcomes:
measure: Maximum Serum Concentration(Cmax)
timeFrame: Serum concentrations of YH35324 will be observed for 57 days after administration
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 57 days after administration
measure: Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf)
timeFrame: Serum concentrations of YH35324 will be observed for 57 days after administration
measure: Time to Maximum Serum Concentration (Tmax)
timeFrame: Serum concentrations of YH35324 will be observed for 57 days after administration
measure: Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2)
timeFrame: Serum concentrations of YH35324 will be observed for 57 days after administration
measure: Apparent Serum Clearance (CL/F)
timeFrame: Serum concentrations of YH35324 will be observed for 57 days after administration
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Serum concentrations of YH35324 will be observed for 57 days after administration
measure: Change in serum total IgE level
timeFrame: Change in serum total IgE will be observed for 57 days after administration
measure: Change in FcƐRI expression on basophil surface
timeFrame: Change in FcƐRI expression on basophil surface will be observed for 57 days after administration
measure: Change in serum soluble FcƐRI concentration
timeFrame: Change in serum soluble FcƐRI concentration will be observed for 57 days after administration
measure: Change in serum Mas-related G protein-coupled receptor-X2 (MRGPRX2) concentration
timeFrame: Change in serum Mas-related G protein-coupled receptor-X2 (MRGPRX2) concentration will be observed for 57 days after administration
measure: [Parts 1 and 2 only] Change in Basophil Histamine Release Assay (BHRA)
timeFrame: Change in Basophil Histamine Release Assay (BHRA) will be observed for 57 days after administration
measure: Change in the Urticaria Control Test (UCT) score
timeFrame: Change in the Urticaria Control Test (UCT) score will be observed for 57 days after administration
measure: Rate of Use of rescue medications
timeFrame: Use of rescue medications will be observed for 57 days after administration
measure: [Parts 1 and 2 only] Change in weekly Hive Severity Score 7 (HSS7)
timeFrame: Change in weekly Hive Severity Score 7 (HSS7) will be observed for 57 days after administration
measure: [Parts 1 and 2 only] Change in weekly Itch Severity Score 7 (ISS7)
timeFrame: Change in weekly Itch Severity Score 7 (ISS7) will be observed for 57 days after administration
measure: [Parts 1 and 2 only] Change in weekly Urticaria Activity Score 7 (UAS7)
timeFrame: Change in weekly Urticaria Activity Score 7 (UAS7) will be observed for 57 days after administration
measure: [Part 3 only] Change in Critical Temperature Thresholds (CTT) in response to the challenge test (TempTest® 4)
timeFrame: Change in Critical Temperature Thresholds (CTT) in response to the challenge test (TempTest® 4) will be observed for 57 days after administration
measure: [Part 3 only] Change in the Peak Pruritus Numerical Rating Scale (PP-NRS) score after the challenge test (TempTest® 4)
timeFrame: 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
measure: Incidence of serum anti-YH35324 antibodies
timeFrame: Incidence of serum anti-YH35324 antibodies will be observed for 57 days after administration
Locations:
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggi-do
city: Hwaseong-si
country: Korea, Republic of
facility: Hallym University Dongtan Sacred Heart Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center
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: Busan
country: Korea, Republic of
facility: Dong-a University hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
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: