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

NCT04077736 | Completed Phase 2

• 1 other identifier: 2019PHB089-02
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsing Polychondritis

Keywords

Relapsing polychondritis，IL-2

Outcome Measures

Primary Outcomes (1)

• Foxp3+Treg cells: change in percentage of total lymphocytes

  Treg refers to regulatory T cells

  week 12

Secondary Outcomes (2)

• Relapsing Polychondritis Disease Activity Index

  week 12

• safety assessment

  week 12

Study Arms (1)

Interleukin-2

EXPERIMENTAL

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

Interventions

Interleukin-2 DRUG

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).

Also known as: Recombinant Human Interleukin-2

Interleukin-2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 and ≤70 years
• Meet the revised Michet criteria
• 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

You may not qualify if:

• Any subject who meets any of the following criteria shall be excluded:
• Use rituximab or other monoclonal antibodies within 1.6 months.
• months after treatment with high dose glucocorticoid (\> 1 mg/kg/d).
• Serious complications: heart failure (≥ New York Heart Association（NYHA） III grade), renal insufficiency (creatinine clearance rate ≤ 30 ml/min), liver function insufficiency (serum alanine transaminase or glutamic-pyruvic transaminaseT \> 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, Epstein-Barr 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. Bacillus Calmette-Guerin 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Department of Rheumatology and Immunology, Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

MeSH Terms

Conditions

Polychondritis, Relapsing

Interventions

Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Cartilage Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Li Zhanguo

  Peking University Institute of Rheuamotology and Immunology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proffesor

Study Record Dates

• First Submitted: September 1, 2019
• First Posted: September 4, 2019
• Study Start: November 1, 2019
• Primary Completion: October 10, 2023
• Study Completion: October 30, 2023
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)