Low-dose IL-2 Treatment on Behcet's Disease

NCT04065672 | Completed Phase 2 DMC

• 1 other identifier: 2019PHB089-03
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to explore the clinical and immunological efficacy of low-dose IL-2 on Behcet's Disease.

Conditions

Behcet's Disease

Keywords

Behçet's syndrome; LD-IL-2 therapy; Treg cells; T follicular cells; Th17 cells

Outcome Measures

Primary Outcomes (1)

• the number of oral ulcers at week 12

  the number of oral ulcers at week 12

  Week 12

Secondary Outcomes (7)

• the change in pain from oral ulcers from baseline to week 12

  Week 12 and Week 24

• Change from baseline in the Behçet's Syndrome Activity Score

  Week 12 and Week 24

• Change from baseline in simplified Behcet Disease Current Activity Form (BDCAF) Score

  Week 12 and Week 24

• Change from baseline in Protocol-specific immunophenotypic analysis of peripheral blood lymphocyte subsets

  Week 12 and Week 24

• the number of genital ulcers at week 12 and Week 24

  Week 12 and Week 24

Study Arms (2)

Low-dose IL-2

EXPERIMENTAL

After a 4-week screening period, patients received IL-2 at a dose of 1 million IU subcutaneously every other day. After the initiation of the therapy, patients could continue with concurrent medication but were prohibited from changing or adding immunosuppression therapy during the course of the study with a 12-week observational followed up.

Drug: Low-dose IL-2

placebo

PLACEBO COMPARATOR

After a 4-week screening period, patients received placebo subcutaneously every other day. After the initiation of the therapy, patients could continue with concurrent medication but were prohibited from changing or adding immunosuppression therapy during the course of the study with a 12-week observational followed up.

Drug: Placebo

Interventions

Low-dose IL-2 DRUG

After a 4-week screening period, patients received IL-2 at a dose of 1 million IU subcutaneously every other day. After the initiation of the therapy, patients could continue with concurrent medication but were prohibited from changing or adding immunosuppression therapy during the course of the study with a 12-week observational followed up.

Low-dose IL-2

Placebo DRUG

After a 4-week screening period, patients received placebo subcutaneously every other day. After the initiation of the therapy, patients could continue with concurrent medication but were prohibited from changing or adding immunosuppression therapy during the course of the study with a 12-week observational followed up.

placebo

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 18-70 years of age at time of screening.
• Diagnosis of Behçet's Disease (according to the 1989 ICBD) for ≥3 months before screening.
• Active oral ulcer at time of screening.
• Patients on corticosteroids (≤1 mg/kg/d prednisone or equivalent), DMARDs (e.g. methotrexate, hydroxychloroquine, azathioprine, MMF, leflunomide, ciclosporin etc.), must have been on a stable dose for 4 weeks prior to receiving the first infusion of study medication and expected to remain on this dose throughout the study. If the registered doctor plans to quit using current DMARDs or glucocorticoids, the washout period needs to be followed before patients join the groups. Each drug needs to meet the following washout period
• glucocorticoids - 2 weeks
• DMARDs (including mmethotrexate, hydroxychloroquine, azathioprine, MMF, leflunomide, and ciclosporin ) - 4 weeks
• IVIg or cyclophosphamide - 2 months
• Rituximab - 6 months
• other bDMARDs(e.g. Infliximab, Adalimumab, Enanercept etc.) - 12 weeks
• Given their written informed consent to participate in the trial and expected to be able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• BD-related active major organ involvement requiring immunosuppressive therapy, e.g., pulmonary (e.g., pulmonary artery aneurysm), vascular (e.g., thrombophlebitis, recurrent malignant aneurysms), gastrointestinal (e.g., gastrointestinal ulcers), and central nervous system (e.g., meningoencephalitis).
• High-dose glucocorticoid (\>1mg/kg/d) usage within 1 month.
• Severe comorbidities: including Heart failure (≥ grade III NYHA); Renal insufficiency (creatinine clearance ≤30 ml/min); Hepatic insufficiency (serum ALT or AST \>3 times the ULN, or total bilirubin \>ULN for the central laboratory conducting the test).
• Other severe, progressive or uncontrolled hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis).
• Known allergies, hypersensitivity, or intolerance to IL-2 or its excipients.
• History of severe allergic reaction to monoclonal antibodies or to murine, chimeric, or human proteins or their excipients.
• Had a severe infection (including, but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis); had been hospitalized for an infection; or had been treated with IV antibiotics for an infection, within 2 months prior to the first administration of study agent.
• Chest radiograph within 3 months prior to the first administration of study agent that showed an abnormality suggestive of a malignancy or current active infection, including TB.
• Infected with HIV (positive serology for HIV antibody) or hepatitis C (positive serology for Hep C antibody). If seropositive, consultation with a physician with expertise in the treatment of HIV or hepatitis C virus infection was recommended.
• Infected with hepatitis B virus. For patients who were not eligible for this study due to hepatitis B virus test results, consultation with a physician with expertise in the treatment of hepatitis B virus infection was recommended.
• Had any known malignancy or has a history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that had been treated with no evidence of recurrence for ≥3 months before the first study agent administration or cervical neoplasia with surgical cure).
• Had uncontrolled psychiatric or emotional disorder, including a history of drug and alcohol abuse within the past 3 years that might prevent the successful completion of the study.
• Received, or was expected to receive, any live virus or bacterial vaccination within 3 months before the first administration of study agent, during the study, or within 4 months after the last administration of study agent. Had a BCG vaccination within 12 months of screening.
• Pregnancy, lactation or women of child-bearing potential (WCBP) unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment has finished.
• Men whose partners are of child-bearing potential but who are unwilling to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment has finished.

Sponsors & Collaborators

• HeJing: lead

Study Sites (1)

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

Beijing, China

Location

Related Publications (4)

• Gunduz E, Teke HU, Bilge NS, Cansu DU, Bal C, Korkmaz C, Gulbas Z. Regulatory T cells in Behcet's disease: is there a correlation with disease activity? Does regulatory T cell type matter? Rheumatol Int. 2013 Dec;33(12):3049-54. doi: 10.1007/s00296-013-2835-8. Epub 2013 Aug 3.

  PMID: 23912800 BACKGROUND

• Nanke Y, Kotake S, Goto M, Ujihara H, Matsubara M, Kamatani N. Decreased percentages of regulatory T cells in peripheral blood of patients with Behcet's disease before ocular attack: a possible predictive marker of ocular attack. Mod Rheumatol. 2008;18(4):354-8. doi: 10.1007/s10165-008-0064-x. Epub 2008 Apr 22.

  PMID: 18427720 BACKGROUND

• Mohammadi M, Shahram F, Shams H, Akhlaghi M, Ashofteh F, Davatchi F. High-dose intravenous steroid pulse therapy in ocular involvement of Behcet's disease: a pilot double-blind controlled study. Int J Rheum Dis. 2017 Sep;20(9):1269-1276. doi: 10.1111/1756-185X.13095. Epub 2017 May 19.

  PMID: 28524639 BACKGROUND

• Zou J, Ji DN, Shen Y, Guan JL, Zheng SB. Mucosal Healing at 14 Weeks Predicts better Outcome in Low-dose Infliximab Treatment for Chinese Patients with Active Intestinal Behcet's Disease. Ann Clin Lab Sci. 2017 Mar;47(2):171-177.

  PMID: 28442519 BACKGROUND

Related Links

• Primary outcome for BD patients

MeSH Terms

Conditions

Behcet Syndrome

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vascular

Intervention Hierarchy (Ancestors)

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

Study Officials

• Zhanguo Li, MD,PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigators and the study participants were masked to the allocation sequence and the intervention (study drug containing IL-2 or placebo). The study drug was packaged, labeled, and randomly assigned by an independent third party (Beijing Stemexel Technology Co).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 20, 2019
• First Posted: August 22, 2019
• Study Start: October 12, 2021
• Primary Completion: April 20, 2023
• Study Completion: July 28, 2023
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)