A Phase 2 Study of Lesigercept (YH35324) in Adult Patients with Chronic Spontaneous Urticaria (CLEAR)

Who can take part

• Diagnosis of CSU for at least 6 months prior to screening
• Diagnosis of CSU inadequately controlled on 2nd-generation H1-antihistamines at the time of randomization (Day 1) defined as meeting all of the following: • Presence of itch and hives for > 6 consecutive weeks at any time point prior to screening despite use of 2nd-generation H1-antihistamines • Stable dose of 2nd-generation H1-antihistamines for at least 7 days prior screening and able to continue on the same H1-antihistamine maintenance therapy at the daily stable dose during the study • UAS7≥16, ISS7≥8 (at least 1 point/day) and HSS7≥8 (at least 1 point/day), each during the 7 consecutive days prior to randomization
• Women of childbearing potential must have a negative pregnancy test at screening, agree to use acceptable methods of contraception from the time of screening until 6 months after the last dose of study treatment, and must not be breastfeeding
• Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception from the start of dosing until 6 months after the last dose of study treatment and refrain from donating sperm during this period
• Male or female adults aged ≥ 18 to ≤ 75 years (or the legal age of consent in the jurisdiction in which the study is taking place)
• Participants with ≥ 80% compliance to 2nd-generation H1-antihistamines during the screening period
• Participants should sign the Informed Consent Form (ICF) prior to any study-specific procedures, which include compliance with the requirements and restrictions specified in the ICF and protocol

Who cannot take part

• Use of biological agents (e.g., anti-IgE antibodies, anti-IL-4/IL-13 antibodies, anti-IL-5 antibodies, etc.) within 4 months or 5 half-lives prior to randomization (Day 1), whichever is longer
• Regular use (i.e., daily or every other day for ≥5 consecutive days) of doxepin within 2 weeks prior to randomization
• Regular Use (i.e., daily or every other day for ≥5 consecutive days) of H2 antihistamines or leukotriene receptor antagonists within 1 week prior to randomization
• Regular use (i.e., daily or every other day for ≥5 consecutive days) of systemic or topical corticosteroids, hydroxychloroquine, methotrexate, cyclosporine, azathioprine, cyclophosphamide, tacrolimus, or mycophenolate mofetil within 4 weeks prior to randomization Note: Other corticosteroid preparations with limited systemic exposure, specifically for non-CSU indications only (e.g., intranasal or any topical corticosteroids), are permitted for use on an as-needed basis
• Administration of a live vaccine within 4 weeks prior to randomization
• Intravenous immunoglobulin G or plasmapheresis within 4 weeks prior to randomization
• Major surgery within 8 weeks prior to screening or scheduled surgery during the study
• (Applicable in Japan only) Use of neurotropin, glycyrrhizin, tranexamic acid, or herbal medications when used to treat urticaria within 2 weeks prior to randomization
• Use of another investigational product within 5 half-lives or 30 days prior to randomization, whichever is longer
• Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to screening), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant
• History of drug or alcohol abuse within 6 months prior to randomization
• History of treated or untreated malignant tumor in any organ system within 5 years from screening regardless of presence of evidence for local recurrence or metastasis (except for cured squamous cell carcinoma of the skin, basal cell carcinoma, and cervical carcinoma in situ)
• Clearly defined underlying etiology chronic urticaria other than CSU (main manifestation being physical urticaria). This included but was not limited to the following urticarias: • Inducible urticaria: acute urticaria, solar, cholinergic, heat, cold, aquagenic, vibratory angioedema, symptomatic dermographism, delayed pressure, or contact • Other diseases with symptoms of urticaria or angioedema: systemic lupus erythematosus, urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, or generalized cancer
• Any other skin diseases related to chronic itching that may affect the study assessments and results as determined by the investigator (e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or psoriasis) or skin diseases related to wheals without pruritus (e.g., asymptomatic dermatographism)
• History of hypersensitivity or anaphylaxis or contraindication to any active or inactive ingredient of the IP, drugs of the similar class to the IP (e.g., antibodies, fusion proteins), H1-antihistamines, and epinephrine, or a history of anaphylaxis
• Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection (living in an endemic area, chronic GI symptoms, travel within the last 6 months to an endemic area and/or chronic immunosuppression)
• Medical examination or laboratory findings that suggest the possibility of decompensation of co-existing conditions for the duration of the study. Any items that are cause for uncertainty will be reviewed with the investigator
• Known or suspected ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis) or laboratory evidence of chronic viral Infections, including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV), as evidenced by positive confirmatory laboratory tests and/or medical history
• Participants who are not able to comply with the study procedures, restrictions, and requirements, as determined by the investigator