Low-dose Recombinant Human IL-2 for the Treatment of Relapsing Polychondritis

Study Overview
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Brief Summary
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Relapsing polychondritis (RP) is a rare, systemic autoimmune disorder characterized by episodic inflammation of cartilaginous structures. Pro-inflammatory chemokines involved in the recruitment of monocytes and modulation of macrophage function, such as monocyte chemoattractant protein-1, macrophage inflammatory protein 1β, and interleukin (IL)-8, are significantly elevated in active RP compared with controls.The activation of monocytes and macrophages may play an important role in the pathophysiology of RP. The levels of serum Th1 cytokines (interferon, IL-2 (IL-2) and IL-12 (IL-12) were significantly correlated with disease status，which suggested that RP may be a Th1-mediated disease process. IL-2 is a kind of lymphocyte growth factor. At lower doses, regulatory T cells exhibit dominant amplification because of their more sensitivity to IL-2. Regulatory T cells can inhibit the growth of effector T cells and then play an immunosuppressive role. The investigators hypothesized that low-dose IL-2 could be a novel therapy in active RP patients. This clinical study will explore the efficacy and immunological evaluation of low dose IL-2 in the treatment of RP.

Detailed Description
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Ten patients with active RP at 18 to 70 years of age were enrolled. Without changing the original treatment plan, IL-2 1 million units was administered subcutaneously five days every week for 4 weeks and then once a week for 8 weeks. All patients were followed up for 3 months after treatment. The clinical symptoms, disease score scale, laboratory parameters, immune cell subsets and cytokines should be monitored during the treatment and follow-up.

Official Title
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A Pilot Study of Low Dose IL-2 in the Treatment of Relapsing Polychondritis

Conditions
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Relapsing Polychondritis

Intervention / Treatment
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* Drug: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 and ≤70 years Meet the revised Damiani criteria of 1979 Patients had an inadequate response to standard treatment for ≥ 4 weeks. The background treatment included corticosteroids (≤0.5 mg/ kg), immunosuppressants ( methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil leflunomide, or cyclophosphamide) Negative urine pregnancy test Written informed consent form Exclusion Criteria: Any subject who meets any of the following criteria shall be excluded: Use rituximab or other monoclonal antibodies within 1.6 months. 1 months after treatment with high dose glucocorticoid (> 1 mg/kg/d). Serious complications: heart failure (≥ NYHA III grade), renal insufficiency (creatinine clearance rate ≤ 30 ml/min), liver function insufficiency (serum ALT or AST > 3 times normal upper limit, or total bilirubin > normal upper limit) Other serious, progressive or uncontrollable hematological, gastrointestinal, endocrine, lung, heart, nerve, or brain diseases (including demyelination diseases, such as multiple sclerosis). Known allergies, hyperresponsiveness or IL-2 or its excipients are intolerant. Severe infections (including, but not limited to, hepatitis, pneumonia, bacteremia, pyelonephritis, EB virus, tuberculosis infection), hospitalization for infection, or intravenous antibiotics 2 months before the first dose of treatment. Chest imaging showed abnormalities in malignant tumors or current active infections (including tuberculosis) within 3 months before the first use of the study. Infected with HIV (HIV antibody positive serology) or hepatitis C (Hep C antibody positive serology). If seropositive, consult a doctor with expertise in the treatment of HIV or hepatitis C virus infection. There has been any known malignant tumor or history of malignant tumor in the past 5 years (with the exception of non-melanoma skin cancer, non-melanoma skin cancer with no sign of recurrence or surgically cured cervical tumor within 3 months of use of the first study preparation). There are uncontrolled mental or emotional disorders, including a history of drug and alcohol abuse over the past three years, which may hinder the successful completion of the study. Within 3 months before the first injection of the research agent, during the study period or within 4 months after the last injection of the research agent, any live virus or bacterial vaccine is received or expected to be received. BCG was vaccinated within 12 months after screening. Pregnant and lactating women (WCBP) are reluctant to use medically approved contraceptives during and 12 months after treatment. Men whose partners have fertility potential but do not want to use appropriate medically approved contraceptives during and within 12 months of treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interleukin-2<br>low dose interleukin-2 injected subcutaneously, at a dose of 1 million IU five days per week for 4 weeks (day1-5, 8-12, 15-19, 22-26) and then once a week for 8 weeks (day33, 40, 47, 54, 61, 68, 75, 82). | Drug: Interleukin-2<br>* low dose interleukin-2 injected subcutaneously, at a dose of 1 million IU five days per week for 4 weeks (day1-5, 8-12, 15-19, 22-26) and then once a week for 8 weeks (day33, 40, 47, 54, 61, 68, 75, 82). Then all patients were followed up for 3 months<br>* Other names: Recombinant Human Interleukin-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Foxp3+Treg cells: change in percentage of total lymphocytes | Treg refers to regulatory T cells | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RPDAI | Relapsing Polychondritis Disease Activity Index | week 12 | 
| safety assessment | Adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor,drug-induced liver and kidney damage. | week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing polychondritis，IL-2