Efficacy of Low-dose Interleukin-2 Treatment in Chronic Spontaneous Urticaria

NCT ID: NCT04893980

Last Updated: 2021-05-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-16
• Study Completion Date: 2022-12-01

Brief Summary

This study is a randomized, controlled, single-center clinical study to evaluate the short-term efficacy of low-dose Interleukin-2 injection as an add-on therapy for the treatment of patients aged 18-75 who have been diagnosed with CSU and remain symptomatic despite oral antihistamine treatment .

Detailed Description

Backgrounds:

Urticaria is a common disorder that present with localized edema reaction caused by dilatation and increased permeability of small blood vessels in skin and mucosa. The main clinical manifestations are wheal and erythema reaction.

Chronic spontaneous urticaria (CSU) is defined as the recurrent, transient (<24h), pruritic wheals of the skin and mucosa lasting for more than 6 weeks ,with or without angioedema, excluding chronic inducible urticaria and urticarial vasculitis. Among all patients with chronic urticaria, CSU patients accounts for about 80%. Although the pathogenesis of CSU is still unclear, increasing evidence has shown an autoimmune feature of this chronic disease. Oral antihistamines are the mainstay of treatment for patients with CSU. However, a proportion of patients with CSU remain symptomatic despite treatment with standard- or doubled-dose of antihistamines. In recent years, studies have shown that low-dose recombinant human IL-2 (rhIL-2) treatment has good therapeutic effect in a variety of autoimmune diseases, such as systemic lupus erythematosus, type 1 diabetes, without serious side reactions. Therefore, we propose low-dose rhIL-2 as an add-on treatment for patient with CSU that are recalcitrant to treatment with antihistamines. Here we designed this clinical trial to explore its therapeutic effect as well as therapeutic mechanisms.

Design of Study:

This is a randomized, controlled, single-center clinical trial to assess the short-term efficacy of rhIL-2 treatment for patients with CSU.

Methods:

RhIL-2 injection combined with the current dose of antihistamine (Use one kind or two to three kinds in combination, and use one or two doses of each kind of antihistamine，keeping doses before enrollment) will be applied to CSU patients meeting the inclusion criteria. The end points include clinical response and immunological changes, as well as safety.

Conditions

Chronic Spontaneous Urticaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low-dose interleukin-2 treatment group

Use Interleukin-2 to treat CSU during day1-day28.

Group Type: EXPERIMENTAL

Recombinant human interleukin-2 (rhIL-2)

Intervention Type: DRUG

During Day 0-14, patients in this group will receive treatment with antihistamines at the same dosage as pre-recruitment, together with a low-dose recombinant human Interleukin-2 (rhIL-2) at a dosage of 1 million international units every other day by intramuscular injection (rhIL-2, 1 MIU, im, Qod). During Day 15-28, the injections of rhIL-2 will be continued at the same dosage and the dose of antihistamines may be adjusted according to the control of symptoms.

Control group

Use Interleukin-2 to treat CSU during day15-day28.

Group Type: OTHER

Control group

Intervention Type: DRUG

During Day 0-14, patients in the control group receive treatment with only antihistamines at the same dosage as pre-recruitment, but no injection of rhIL-2. During Day 15-28, treatment with low dose recombinant human Interleukin-2 (rhIL-2), i.e., 1 million international units every other day by subcutaneous or intramuscular injection (rhIL-2, 1MIU, im, Qod), will be added.

Interventions

Recombinant human interleukin-2 (rhIL-2)

During Day 0-14, patients in this group will receive treatment with antihistamines at the same dosage as pre-recruitment, together with a low-dose recombinant human Interleukin-2 (rhIL-2) at a dosage of 1 million international units every other day by intramuscular injection (rhIL-2, 1 MIU, im, Qod). During Day 15-28, the injections of rhIL-2 will be continued at the same dosage and the dose of antihistamines may be adjusted according to the control of symptoms.

Intervention Type: DRUG

Control group

During Day 0-14, patients in the control group receive treatment with only antihistamines at the same dosage as pre-recruitment, but no injection of rhIL-2. During Day 15-28, treatment with low dose recombinant human Interleukin-2 (rhIL-2), i.e., 1 million international units every other day by subcutaneous or intramuscular injection (rhIL-2, 1MIU, im, Qod), will be added.

Intervention Type: DRUG

Other Intervention Names

Recombinant Human Interleukin-2 (I); No injections during Day 0-14

Eligibility Criteria

Inclusion Criteria

1. Age: between 18- and 75-years old;

2. Patients definitely diagnosed with chronic spontaneous urticaria according to 'Guideline for diagnosis and treatment of urticaria in China (2018) '; or chronic spontaneous urticaria has been diagnosed in the past.

3. Patients taking antihistamines daily ( one kind or two to three kinds in combination, with a standard- or doubled-dose of each kind of antihistamines) for at least one week and remain symptomatic with a UAS7 score of not less than 16;

4. Written informed consent was obtained, and the patient volunteers to participate in the project and complete the project as required.

Exclusion Criteria

1. Patients with severe diseases of heart, brain, lungs, liver, kidney or blood system; patients experienced organ transplantation;

2. Patients with any acute severe infection such as pyemia and cellulitis, active tuberculosis, or an infection history of human immunodeficiency virus (HIV);

3. Patients have a clear history of allergy to rhIL-2;

4. Patients receiving Interleukin-2 treatment in the last 3 months by subcutaneous or intramuscular injection；

5. Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment;

6. Pregnant women, lactating women or women who are willing to conceive within 3 months;

7. Patients receiving glucocorticoid treatment in the last 4 weeks; Patients receiving cyclosporin treatment in the last 90 days；Patients receiving tripterygium wilfordii polyglycoside treatment in the last 6 months；Patients receiving Omalizumab treatment in the last 1 year；Other drugs used previously should be identified whether they are in the washout period one by one, and patients who have taken drugs that may have an impact on the study should be excluded during the washout period or screened again for enrollment after the washout period；

8. Patients who have participated in other clinical trials within 3 months before the screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Qianjin Lu, MD, PhD

Professor and Director, Institute of Dermatology, Central South University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qianjin Lu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The Second Xiangya Hospital, Central South University

Locations

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Countries

China

Central Contacts

Qianjin Lu

Role: CONTACT

qianlu5860@gmail.com

13787097676

Hai Long

Role: CONTACT

dr.hailong@csu.edu.cn

18229743206

Facility Contacts

zhuo Li

Role: primary

xiangyagcp@126.com

+86-731-84896038

Hai Long

Role: backup

dr.hailong@csu.edu.cn

18229743206

Other Identifiers

CSU202009

Identifier Type: -

Identifier Source: org_study_id