A Multicenter, Randomized, Double-blind, Placebo-Controlled Parallel Study：Clinical Study of Efficacy and Safety of Histamine Human Immunoglobulin (ShuYangMinNing) in the Treatment of Chronic Spontaneous Urticaria (CSU)
Overview
- Phase
- Phase 4
- Status
- Not yet recruiting
- Sponsor
- Hangzhou Grand Biologic Pharmaceutical, Inc.
- Enrollment
- 252
- Primary Endpoint
- Disease control rate during the last week of treatment (i.e., proportion of patients with urticaria activity score for 7d（UAS7，range 0-42) < 7 for 7 consecutive days after the last injection)
Overview
Brief Summary
The goal of this clinical trial is to study patients with chronic spontaneous urticaria. The main question it aims to answer is the efficacy and safety of histamine human immunoglobulin (ShuYangMinNing) in the treatment of chronic spontaneous urticaria.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent must be obtained before any assessment is performed；
- •Age ≥ 18 years；
- •Meet the diagnostic criteria of chronic spontaneous urticaria from《Guideline for diagnosis and treatment of urticaria in China（2022）》and follow the doctor's advice；the patient had urticaria symptoms in the previous week before enrollment, and UAS7 score(range 0-42) ≥ 7;
- •Patients with uncontrolled urticaria are regularly treated with standard single-dose antihistamines regularly for 2 weeks before screening;
Exclusion Criteria
- •Pregnant or nursing (lactating) women;
- •Patients with malignant tumors, severe liver and kidney diseases, hematological disorders, autoimmune diseases(such as systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis, myositis, systemic vasculitis, systemic sclerosis, rheumatoid arthritis, spondyloarthropathy or other rheumatic immune diseases evaluated by the physician that are not suitable for inclusion), chronic serious infections, diabetic peripheral neuropathy, psychosis, and other diseases or medical histories that may affect normal efficacy evaluation and/or subject safety evaluation；
- •History of drug or alcohol abuse;
- •Patients who discontinue systemic use of glucocorticoids and other immunosuppressants(such as cyclosporin A, wilfordii , etc.) that affect immune function for less than 4 weeks;Patients who discontinue systemic use of biologics (e.g., omalizumab) for less than 3 months;
- •Patients with symptoms of urticaria and/or angioedema, Including but not limited to urticaria vasculitis, serum sickness like reaction, bullous pemphigoid, mastocytosis, neutrophilic urticaria dermatosis, Schnitzler syndrome, autoinflammatory response syndromes (e.g., tumor necrosis factor receptor-associated periodic fever syndrome, familial Mediterranean fever, mevaldate kinase deficiency, etc.);or other chronic itchy skin conditions, such as atopic dermatitis, dermatitis herpetiformis, and pruritus senile;
- •Allergic to human immunoglobulin;
- •History of other severe allergic reactions;
- •Patients with pathological arrhythmias and a history of organic heart disease; Patients with known or suspected QT prolongation; or patients who are unable to discontinue medications that cause QT prolongation during the trial；
- •Subjects whom the investigator considers unsuitable for other reasons.
Arms & Interventions
Treatment
Treatment arm will receive a dose of Histamine Human Immunoglobulin 12mg (2ml) s.c. which consists of one injection of Histamine Human Immunoglobulin 12mg(2ml) vial every week for 4 times.
Treatment arm will also receive a dose of loratadine p.o. which consists of one pill of loratadine 10mg every day for 4 weeks.
Intervention: human histaglobulin (Biological)
Treatment
Treatment arm will receive a dose of Histamine Human Immunoglobulin 12mg (2ml) s.c. which consists of one injection of Histamine Human Immunoglobulin 12mg(2ml) vial every week for 4 times.
Treatment arm will also receive a dose of loratadine p.o. which consists of one pill of loratadine 10mg every day for 4 weeks.
Intervention: Loratadine 10 Mg (Drug)
Placebo
Placebo arm will receive placebo which consists of one injection of placebo 12mg(2ml) vial every week for 4 times.
Placebo arm will also receive a dose of loratadine p.o. which consists of one pill of loratadine 10mg every day for 4 weeks.
Intervention: placebo (Biological)
Placebo
Placebo arm will receive placebo which consists of one injection of placebo 12mg(2ml) vial every week for 4 times.
Placebo arm will also receive a dose of loratadine p.o. which consists of one pill of loratadine 10mg every day for 4 weeks.
Intervention: Loratadine 10 Mg (Drug)
Outcomes
Primary Outcomes
Disease control rate during the last week of treatment (i.e., proportion of patients with urticaria activity score for 7d（UAS7，range 0-42) < 7 for 7 consecutive days after the last injection)
Time Frame: through study completion, an average of 1 year
The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) . The daily UAS is calculated as the average of the morning and evening scores. The urticaria activity score for 7d (UAS7) is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. If UAS7 score is less than 7, it indicates disease control. A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. The primary outcome measure was disease control rate in the last week of treatment. Chi-square test was used for comparison between groups. Based on the analysis for the main full analysis set (FAS), based on the analysis of the per protocol set（PPS) for supporting analysis.
Secondary Outcomes
- Time when UAS7 (range 0-42) <7 for the first time(up to 5 weeks)
- Changes in UAS7 scores(range 0-42) after each dose compared with baseline(up to 5 weeks)
- Change in chronic urticaria quality of life questionnaire (CU-Q2oL) score from baseline(up to 5 weeks)
- Proportion of patients who responded to treatment as assessed by UCT score(up to 5 weeks)
- Proportion of patients with well-controlled disease as assessed by UCT score(up to 5 weeks)
- Proportion of patients who developed respiratory infections(up to 10 weeks)