The goal of this clinical trial is to learn if human interleukin-2 (IL-2) works to treat moderate to severe chronic spontaneous urticaria in adults who remain symptomatic despite oral antihistamine treatment (refractory CSU). It will also learn about the safety of IL-2. The main questions it aims to answer are: Does IL-2 alleviate the symptoms of urticaria in patients? What medical problems do participants have when given IL-2? Researchers will compare IL-2 to a placebo (a look-alike and smell-like substance that contains no IL-2) to see if IL-2 works to treat refractory, moderate to severe CSU. Participants will: Receive IL-2 or a placebo intramuscular injections for 3 rounds at Week 0, 4 and 8, in which each round includes one injection daily for seven consecutive days. Visit the clinic for checkups and tests at Week 2, 4, 8, 12 and 24. Keep a diary of their symptoms and the number of tablets of oral antihistamines.
Background: Urticaria is a common disorder characterized by localized edema due to dilation and increased permeability of small blood vessels in the skin and mucous membranes. The primary clinical manifestations include wheals and pruritus. Chronic spontaneous urticaria (CSU) is defined as recurrent, transient (\<24 hours), pruritic wheals on the skin and mucosa lasting for more than 6 weeks, with or without angioedema, excluding chronic inducible urticaria. Among patients with chronic urticaria, about 2/3 have CSU. Although the pathogenesis of CSU remains unclear, increasing evidence suggests an autoimmune feature of this disorder. Oral antihistamines are the primary treatment for CSU, yet some patients continue to experience symptoms despite treatment with standard or double doses. Recent studies have shown that human IL-2 (Interleukin-2) can be effective in a proportion of CSU patients refractory to antihistamine treatment, without significant side effects. Therefore, in this clinical trial we aim to evaluate the therapeutic effect and safety of this new therapeutic method. Study Design: This is a randomized, placebo-controlled, multi-center clinical trial to evaluate the safety and efficacy of IL-2 treatment in CSU patients who remain symptomatic despite oral antihistamine treatment. Methods: CSU patients who meet the inclusion criteria will receive IL-2 or placebo intramuscular injections in combination with their current antihistamine regimen (either a single antihistamine or a combination of two to three antihistamines at a dose of at least the standard dosage). Endpoints include clinical response, quality of life, and safety profiles.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
124
On the basis of background treatment, intramuscular injection of placebo was added.
On the basis of background treatment, intramuscular injection of human interleukin-2 (I) will be added.
the Second Xiangya Hospital of Central South University
Changsha, Hunan, China
RECRUITINGChange from Baseline in the Urticaria Activity Score of 7 Days（UAS7）at 12 Weeks
This rating requires patients to record the number of wheals and the severity of itching once a day. The sum of each day's UAS score in the past seven consecutive days is UAS7.
Time frame: Baseline and 12 weeks.
Proportion of patients who achieve the treatment target at 2, 4, 8, 12 and 24 weeks, respectively
According to the Expert Consensus on Treat⁃To⁃Target in Chronic Spontaneous Urticaria (2023), published in Chinese Journal of Dermatology, we count the proportion of CSU patients who achieve treatment targets at 2, 4, 8, 12 and 24 weeks post IL-2 or placebo intervention. As stated in Table 1 in the Expert Consensus mentioned above, a CSU patient achieves the treatment target when he meets the following criteria: (1) at 2 weeks post-intervention: UAS7 ≤6, or UAS7 decreased by ≥11 from baseline, or chronic urticaria quality of life questionnaire (CU-Q2oL) score increased by ≥8 from baseline; (2) at 4 weeks or 8 weeks: urticaria control test (UCT) score ≥12, or UAS7 ≤6, or UAS7 decreased by ≥11 from baseline, or CU-Q2oL increased by ≥8 from baseline; (3) at 12 weeks: UCT ≥12, or UAS7 ≤6, or CU-Q2oL increased by ≥19 from baseline; (4) at 24 weeks: UCT =16, or UAS7 =0, or CU-Q2oL increased by ≥19 from baseline.
Time frame: 2, 4, 8, 12 and 24 weeks post-intervention
The change from baseline in UAS7 at 2 weeks and 24 weeks, respectively
This rating requires patients to record the number of wheals and the severity of itching once a day. The sum of the wheal score (range 0-3 points; 0 points refer to no wheals in the day, 1 point refers to ≤ 20 wheals, 2 points refer to 20-50 wheals, and 3 points refer to ≥ 50 wheals in the day) and itching score (range 0-3 points; 0 points=none, 1 point=mild itching, 2 points=moderate itching, 3 points=severe itching) is the UAS score for the day. The sum of scores for seven consecutive days is UAS7.
Time frame: Baseline, 2 weeks, and 24 weeks
Change from baseline in HSS7 score at 2, 12 and 24 weeks, respectively
This rating requires patients to record the number of wheals once daily. The sum of each day's wheal score (range 0-3 points; 0 points refer to no wheals in the day, 1 point refers to ≤ 20 wheals, 2 points refer to 20-50 wheals, and 3 points refer to ≥ 50 wheals in the day) in the past seven consecutive days is HSS7.
Time frame: Baseline, 2 weeks, 12 weeks and 24 weeks
Change from baseline in ISS7 score at 2, 12 and 24 weeks, respectively
This rating requires patients to record the severity of itching once a day. The sum of the itching scores (range 0-3 points; 0 points=none, 1 point=mild itching, 2 points=moderate itching, 3 points=severe itching) in the past seven consecutive days is ISS7.
Time frame: Baseline, 2, 12 and 24 weeks
Change from baseline in Dermatology Life Quality Index (DLQI) from baseline at 2, 12 and 24 weeks, respectively
DLQI has a total of 10 questions, covering symptoms and feelings, daily activities, leisure and entertainment, work and study, interpersonal relationships, and treatment. The score range for each item is 0-3 points. Those who answer no or irrelevant questions will receive 0 points, while those who answer a lot will receive 3 points. The sum of the scores for each question is the total score (ranging from 0 to 30).
Time frame: Baseline, 2, 12 and 24 weeks
Proportion of CSU patients with no disease activity (UAS7=0) and those with low disease activity (UAS7 ≤6) at 2, 12 and 24 weeks, respectively
At each time point (2, 12 and 24 weeks post-intervention), the proportion of CSU patients with UAS7 =0 and the proportion of CSU patients with UAS7 ≤6 are counted, respectively.
Time frame: Baseline, 2, 12 and 24 weeks
Proportion of well-controlled CSU patients (UCT ≥12) and completely controlled CSU patients (UCT=16) at 2, 12 and 24 weeks, respectively
At each time point (2, 12 and 24 weeks post-intervention), the proportion of CSU patients with UCT ≥12 and the proportion of CSU patients with UCT =16 are counted, respectively.
Time frame: Baseline, 2, 12 and 24 weeks
Total number of second-generation antihistamines taken per week at 2, 12 and 24 weeks, respectively
Record the number of second-generation antihistamines tablets/capsules taken by the patient on a daily basis, and add up the number of pills taken each day in the past seven consecutive days to obtain the total number of second-generation antihistamines taken in the previous week.
Time frame: Baseline, 2, 12 and 24 weeks
Proportion of CSU patients receiving systemic corticosteroid treatment and the total duration of systemic corticosteroid treatment during the study
Record the initiation date and cease date of systemic corticosteroid treatment for each subject since their enrollment in interleukin-2/placebo intervention and calculate the duration (dates). The number of subjects who received systemic corticosteroid treatment during the study was calculated, and the total duration (dates) of systemic corticosteroid treatment was summed up in each group.
Time frame: 24 weeks post-intervention or the date of patient withdrawal from the group
Incidence of Adverse Events
Any adverse event is recorded for each subject during the study. Incidence of adverse events, either in total or in separate types of adverse events, is calculated for each treatment group.
Time frame: 12 and 24 weeks
Incidence of Severe Adverse Events
The ratio of the number of cases with severe adverse events to the total number of cases in each treatment group is calculated.
Time frame: 2, 12 and 24 weeks post-intervention
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