Chronic Idiopathic Urticaria, Chronic Spontaneous Urticaria (CSU)
Conditions
Keywords
Chronic spontaneous urticaria, CSU, Chronic hives, THB335, Second-generation H1 antihistamine, Urticaria Activity Score 7, UAS7, Chronic urticaria, Urticaria, Histamine H1 Antagonists
Brief summary
THB335-201 is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in adults with CSU who remain symptomatic despite standard-of-care treatment. The study includes a Screening Period of up to 4 weeks, a 12-week Treatment Period, and a 4-week Follow-Up Period, for a total participant duration of approximately 20 weeks.
Detailed description
This study will evaluate the efficacy and safety of THB335 in adults with chronic spontaneous urticaria (CSU) who continue to have hives and itching despite treatment with a second-generation H1 antihistamine. Approximately 81 participants will be randomly assigned to receive 1 of 2 doses of THB335 or matching placebo orally once daily for 12 weeks, in addition to their stable antihistamine treatment. Neither participants nor study personnel will know the assigned treatment. Participants will then be followed for 4 weeks. The main assessment is the change in weekly Urticaria Activity Score (UAS7) from baseline to Week 12. This study will have approximately 40 locations.
Interventions
DRUGTHB335 Lower Dose
THB335 is an orally administered capsule added to a stable background regimen of a second generation H1 antihistamine.
DRUGTHB335 Higher Dose
THB335 is an orally administered capsule added to a stable background regimen of a second generation H1 antihistamine.
DRUGPlacebo
Placebo is an orally administered capsule added to a stable background regimen of a second generation H1 antihistamine.
Sponsors
Calixis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Males and females 18 through 85 years. * Diagnosis of chronic spontaneous urticaria (CSU) ≥ 6 months. * Active CSU despite treatment with a second-generation H1 antihistamine. * Weekly Urticaria Activity Score (UAS7) ≥ 16 and ISS7 ≥ 8 during the 7 days before randomization, with sufficient electronic diary entries to calculate the baseline scores. * Body mass index of 18 to 38 kg/m² and minimum body weight of 50 kg for male participants or 45 kg for female participants. * Willing and able to complete the daily electronic diary, attend scheduled study visits, and comply with study procedures. * Participants capable of becoming pregnant or producing sperm must agree to follow the protocol-defined contraception requirements. Key
Exclusion criteria
* Chronic urticaria with an identified cause other than chronic spontaneous urticaria. * Another active skin condition associated with chronic itching that could interfere with the study assessments. * Recent treatment with prohibited immunosuppressive therapy, biologic therapy, a Bruton's tyrosine kinase inhibitor, an investigational drug, or another therapy that inhibits the c-KIT receptor. * Clinically significant hepatic, hematologic, or renal disease or laboratory abnormalities. * Active, chronic, or recurrent infection, including human immunodeficiency virus or viral hepatitis infection. * Clinically significant cardiovascular disease or electrocardiogram abnormality, including clinically significant arrhythmia, prolonged QT interval, familial long QT syndrome, or use of medication known to prolong the QT interval that cannot be discontinued. * History of idiopathic anaphylaxis, a severe allergic reaction that may increase the risk of study participation, or hypersensitivity to the study drug or related compounds. * History of malignancy within the previous 5 years, except successfully treated nonmetastatic basal cell or squamous cell skin cancer or carcinoma in situ. * Current or planned use of prohibited medications, including specified inhibitors, inducers, or sensitive substrates of drug-metabolizing enzymes or transporters, or proton pump inhibitors. * Positive urine drug screen at Screening. * Pregnancy or breastfeeding. * Any medical or psychiatric condition that, in the investigator's judgment, could place the participant at increased risk, interfere with the study assessments, or affect the participant's ability to complete the study. Additional eligibility criteria are outlined in the full protocol. The study investigator will review all requirements with potential participants to determine whether they are eligible to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12 | Baseline and Week 12 | UAS7 is the sum of daily Urticaria Activity Scores over 7 days. The daily score combines the Hives Severity Score and Itch Severity Score, each scored from 0 to 3. UAS7 ranges from 0 to 42; higher scores indicate greater disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With UAS7 ≤ 6 | Through Week 12 | UAS7 ranges from 0 to 42. UAS7 ≤ 6 represents well-controlled urticaria. |
| Percentage of Participants With UAS7 = 0 | Week 12 | UAS7 = 0 indicates no reported hives or itching during the 7-day scoring period. |
| Change From Baseline in UAS7 | Baseline to Week 8 | UAS7 ranges from 0 to 42. |
| Change From Baseline in Weekly Itch Severity Score (ISS7) | Baseline to Week 12 | ISS7 is the sum of daily itch-severity scores over 7 days. Daily itch severity is scored from 0 (no itch) to 3 (severe itch); ISS7 ranges from 0 to 21. |
| Change From Baseline in Weekly Hives Severity Score (HSS7) | Baseline to Week 12 | HSS7 is the sum of daily hives-severity scores over 7 days. Daily hives severity is scored from 0 (no hives) to 3 (many hives); HSS7 ranges from 0 to 21. |
| Change From Baseline in Urticaria Control Test (UCT) Score | Baseline and Week 12 | The UCT contains 4 questions scored from 0 to 4. Total scores range from 0 to 16. |
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Through Week 16 | Number and percentage of participants with TEAEs, treatment-related TEAEs, SAEs, AEs leading to discontinuation, and AEs by severity. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Through Week 16 | Clinically significant changes or abnormalities in blood pressure, heart rate, respiratory rate, pulse oximetry, and body temperature will be assessed. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Test Results | Through Week 16 | Clinically significant changes or abnormalities in hematology, chemistry, coagulation, and urinalysis results will be assessed. |
Contacts
CONTACTClinical Trials Monitor
Outcome results
None listed