Interleukin-2 for Refractory Chronic Spontaneous Urticaria (ESIT-CSU)

Central South University

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Chronic Spontaneous Uriticaria

Treatments: Drug: Human interleukin-2 (I) intramuscular injection; Drug: Placebo intramuscular injection

Study type: Interventional

Funder types: Other

Identifiers

NCT06924762

MR-43-25-003708 (Other Identifier)

LYG20240044

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 124 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Gender: Not limited; Age: at least 18 years old and less than 75 years old;
2. Diagnosed with chronic spontaneous urticaria (CSU) (including patients overlapped with chronic inducible urticaria) according to the 2021 EAACI/GA²LEN/EDF/AAAAI guidelines;
3. Disease course of CSU for at least 12 weeks;
4. The patient has been treated with second-generation antihistamines (one or more types, up to 4 tablets per day) every day for 2 weeks or more but still experiences significant symptoms of wheals and/or itching, with a UAS7 score ≥16 or a UCT score <12;
5. UAS7 ≥16 on the date prior to randomization (according to complete daily symptom log data recorded in the past 7 days before randomization);
6. Willing and able to complete daily symptom logs throughout the entire study period;
7. The patient voluntarily consents to participate in this research project and has signed the informed consent.

Exclusion criteria

• Pregnant or breastfeeding women, or women planning to conceive within 6 months;
• Has used corticosteroids, immunosuppressants, leukotriene receptor antagonists, H2 receptor antagonists, intravenous immunoglobulin (IVIG) therapy, and/or undergone plasma exchange in the past 4 weeks;
• Has received omalizumab or other biologic treatments in the past 12 weeks;
• Has previously undergone interleukin-2 treatment;
• Has a history of anaphylactic shock;
• Plans or anticipates the use of any prohibited drugs or treatments during the screening and/or treatment periods;
• Currently has active or recurrent severe infections, such as active tuberculosis;
• Has a congenital or acquired immunodeficiency disorder;
• Has a history of drug or alcohol abuse, mental disorders, or poor compliance, making them unable to adhere to treatment;
• Currently enrolled in another clinical trial;
• Is an employee of the clinical research facility or directly involved in the study, or is an immediate family member of such an individual;
• Any other reason that makes participation in this trial inappropriate.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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124 participants in 2 patient groups, including a placebo group

Interleukin-2 treatment group

Experimental group

Description:

The enrolled subjects will receive three cycles of interleukin-2 treatment in the first 12 weeks upon initiation of the intervention, while continuing with the same oral regimen of second-generation antihistamines as they have been receiving before initiation of the trial. In each cycle of interleukin-2 treatment, the enrolled subjects will receive an intramuscular injection of interleukin-2 at a dosage of 1 million international units, dissolved in 1.0 mL of sterile water for injection, once daily for 7 consecutive days. The three cycles of interleukin-2 treatment will be administered on Day 0\~6, Day 28\~34 and Day 56\~62, respectively.

Treatment:

Drug: Human interleukin-2 (I) intramuscular injection

Placebo group

Placebo Comparator group

Description:

The enrolled subjects will receive three cycles of placebo injections in the first 12 weeks upon initiation of the intervention, while continuing with the same oral regimen of second-generation antihistamines as they have been receiving before initiation of the trial. In each cycle of placebo injections, the enrolled subjects will receive an intramuscular injection of placebo at a same specification as in the IL-2 treatment group, dissolved in 1.0 mL of sterile water for injection, once daily for 7 consecutive days. The three cycles of placebo injections will be administered on Day 0\~6, Day 28\~34 and Day 56\~62, respectively.

Treatment:

Drug: Placebo intramuscular injection