Back to resultsLow-dose IL-2 Treatment on Behcet's Disease
Primary Purpose
Behcet's Disease
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Low-dose IL-2
Sponsored by
About this trial
This is an interventional treatment trial for Behcet's Disease focused on measuring ulcers
Eligibility Criteria
Inclusion Criteria:
- Male or female ≥18 and ≤70 years of age at time of screening;
- Diagnosis of Behcet disease defined by the International Study Group Criteria of 1989;
- Patients who had active disease activity or intolerance after 3 months of conventional therapy; patients who had relapsed disease activity without treatment. Active manifestations including oral ulcers, genital ulcers, arthralgia, skin lesions and other systemic involvement manifestations. Intestinal BD-associated symptoms (abdominal pain, diarrhea, melena, etc.) and endoscopic evidence of active ulcers in the intestine. Aggravated visual acuity on a Snellen chart in at least one eye. Neurological BD (NBD) is classifies as either acute NBD (ANB) or chronic progressive NBD (CPNB) in accordance with the diagnostic criteria for NBD. Vascular BD (VBD) patients have active vasculitis lesions (deep vein thrombosis, aortic lesions, etc.) and abnormalities in inflammatory markers such as serum C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) at enrollment.
- Apply glucocorticoids (≤1.0mg/Kg*d prednisone or equivalent doses of other hormones) for 4 weeks. DMARDs ( methotrexate, hydroxychloroquine, azathioprine, morphine, leflunomide, cyclosporine, mycophenolate mofeti ) need to stable for 4 weeks. Other medications, such as, IVIg and cyclophosphamide need to more than 2 months, Rituximab for 6 months, other biological agents (infliximab, adalimumab, etanercept, anakinra, etc.) for 3 months.
- Have given written informed consent and patients are expected to be able to comply with the requirements of the study follow-up plan and other protocols.
Exclusion Criteria:
- Stable disease activity;
- Received glucocorticoid >1.0mg/Kg*d within 4 weeks, used rituximab within 6 months and other biological agents within 3 months.
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 disease including hematopathy, gastrointestinal disease, endocrinopathy, pulmonary, neuropathy.
- Known allergies, hypersensitivity, or intolerance to IL-2 or its excipients.
- Severe infection, such as hepatitis, HIV, syphilis, pneumonia, bacteremia, cytomegalovirus and so on.
- Malignancy;
- Had uncontrolled psychiatric or emotional disorder;
- Pregnant or breast-feeding.
Sites / Locations
- Department of Rheumatology and Immunology, Peking University People's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Low-dose IL-2
Arm Description
One million units of rhIL-2 was administered subcutaneously five days every week for 4 weeks and then twice a week for 8 weeks. All patients were followed up for 3 months after treatment.
Outcomes
Primary Outcome Measures
Change in Regulatory T cells at week 12 compared to baseline.
Regulatory T cell was examined by flow cytometry and the marker is CD4+CD25+FoxP3+
Secondary Outcome Measures
Change from baseline in Behcet Syndrome Activity Scale (BSAS) Score.
The BSAS score comprises 10 items. Questions about oral ulcers (q1), genital ulcers (q3), skin lesions (q5), and current disease activity (q10) are scored from 0 to 10 (vi- sual analogue scale [VAS]), questions about the number of oral ulcers (q2), genital ulcers (q4), and skin lesions (q6) were scored as 0, 5, or 10, depending on which of the three were checked(0,n=0;5,n=1to3;10,n> 3 for q2 and q4; and n > 5 for q6), and questions about gastrointestinal/eye/vascular symptoms (q7, q8, and q9) were scored as 0 or 10, depending on whether or not they were present. The total score possible is 100.
Change from baseline in physician global assessment activity
Physician's Global Disease Activity (10 cm VAS assessing global disease activity from "No evidence of disease activity" to "Extremely active or severe disease activity"; Disease Activity being defined as potentially reversible pathology or physiology resulting from the Behcet Syndrome
Change from baseline in number of oral and genital ulcers
Ulcers will be examined by a physician.
Change in C-reactive protein from baseline
Change in FoxP3+ Treg cell at week 12 and week 24 compared to baseline.
Change in steroid dose at week 12 and week 24 compared to baseline.
Change from baseline in simplified Behcet Disease Current Activity Form (BDCAF) Score
Simplified BDCAF score comprises 12 items of 10 systemic involvements. Question about headache, oral ulcers, genital ulcers, erythema, skin pustules, joints (arthralgia), joints (athritis), nausea/vomiting/abdominal pain, diarrhea with altered/frank blood per rectum, eye involvement, nervous system involvement, major vessel involvement are scored from 0 or 1 depending on the symptoms of previous 4 weeks by a physician. The total score possible is 12.
Change from baseline in simplified electronic medical record -based activity index (EMRAI).
The EMRAI contains nine symptom scoring items and two laboratory results. Items include oral and genital ulcers, ocular symptoms, skin lesions, epididymitis, and symptoms related to the involvement of joints, the GI tract, the vascular system, and the central nervous system (CNS). laboratory results includ erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP). The presence of each item, ESR and CRP are dichotomised as 0 or 1. The total score possible is 11.
Change from baseline in Behcet's disease ocular inflammatory score 24 (BOS24)
Behcet's disease ocular attack score 24 (BOS24) consists of a total 24 points divided into 6 parameters of ocular inflammatory symptoms, including anterior chamber cells (maximum 4 points), vitreous opacity (maximum 4 points), peripheral fundus lesions (maximum 8 points), posterior pole lesions (maximum 4 points), subfoveal lesions (maximum 2 points), and optic disc lesions (maximum 2 points).
Change from baseline in erythrocyte sedimentation rate
erythrocyte sedimentation rate
Rate of mean change in DAIBD score of 20 or more from baseline.
This primary endpoint applies to intestinal BD patients.The DAIBD will be assessed by collecting information on 8 different intestinal BD-related variables. These 8 variables are: fever, abdominal mass, abdominal tenderness, intestinal complications, extraintestinal manifestations, general well-being, abdominal pain, and total number of liquid stools. The last 3 variables are scored over 7 days by the participant on a diary card. Abdominal pain will be measured using the 11-point numeric rating scale (NRS) to standardize the evaluation of pain and the result of 11-point NRS will be divided into 4 grades (none, mild, moderate, severe) to fill out the DAIBD. where, None indicate 0; Mild indicate 1-3; Moderate indicate 4-6; Severe indicate 7-10.
Rate of equal or more than 20% changes in Visual acuity.
This primary endpoint applies to ocular involvement of BD patients.
Rate of participants without oral and genital ulcers.
Ulcers will be examined by a physician.
Full Information
NCT ID
NCT04065672
First Posted
August 20, 2019
Last Updated
January 14, 2020
Sponsor
Peking University People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04065672
Brief Title
Low-dose IL-2 Treatment on Behcet's Disease
Official Title
Low-dose IL-2 Treatment on Behcet's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 12, 2019 (Actual)
Primary Completion Date
March 20, 2021 (Anticipated)
Study Completion Date
June 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study aims to explore the clinical and immunological efficacy of low-dose IL-2 on Behcet's Disease.
Detailed Description
The investigators designed a single center, open-label, prospective study that routinely administered low-dose IL-2 therapy to monitor the improvement of clinical and laboratory parameters to explore its efficacy and to observe changes in immune cell subsets and cytokines. One million units of rhIL-2 was administered subcutaneously five days every week for 4 weeks and then twice a week for 8 weeks. All patients were followed up for 3 months after treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Behcet's Disease
Keywords
ulcers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low-dose IL-2
Arm Type
Experimental
Arm Description
One million units of rhIL-2 was administered subcutaneously five days every week for 4 weeks and then twice a week for 8 weeks. All patients were followed up for 3 months after treatment.
Intervention Type
Drug
Intervention Name(s)
Low-dose IL-2
Intervention Description
One million units of rhIL-2 was administered subcutaneously five days every week for 4 weeks and then twice a week for 8 weeks. All patients were followed up for 3 months after treatment.
Primary Outcome Measure Information:
Title
Change in Regulatory T cells at week 12 compared to baseline.
Description
Regulatory T cell was examined by flow cytometry and the marker is CD4+CD25+FoxP3+
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Change from baseline in Behcet Syndrome Activity Scale (BSAS) Score.
Description
The BSAS score comprises 10 items. Questions about oral ulcers (q1), genital ulcers (q3), skin lesions (q5), and current disease activity (q10) are scored from 0 to 10 (vi- sual analogue scale [VAS]), questions about the number of oral ulcers (q2), genital ulcers (q4), and skin lesions (q6) were scored as 0, 5, or 10, depending on which of the three were checked(0,n=0;5,n=1to3;10,n> 3 for q2 and q4; and n > 5 for q6), and questions about gastrointestinal/eye/vascular symptoms (q7, q8, and q9) were scored as 0 or 10, depending on whether or not they were present. The total score possible is 100.
Time Frame
Week 12 and Week 24
Title
Change from baseline in physician global assessment activity
Description
Physician's Global Disease Activity (10 cm VAS assessing global disease activity from "No evidence of disease activity" to "Extremely active or severe disease activity"; Disease Activity being defined as potentially reversible pathology or physiology resulting from the Behcet Syndrome
Time Frame
Week 12 and Week 24
Title
Change from baseline in number of oral and genital ulcers
Description
Ulcers will be examined by a physician.
Time Frame
Week 12 and Week 24
Title
Change in C-reactive protein from baseline
Time Frame
Week 12 and Week 24
Title
Change in FoxP3+ Treg cell at week 12 and week 24 compared to baseline.
Time Frame
Week 12 and Week 24
Title
Change in steroid dose at week 12 and week 24 compared to baseline.
Time Frame
Week 12 and Week 24
Title
Change from baseline in simplified Behcet Disease Current Activity Form (BDCAF) Score
Description
Simplified BDCAF score comprises 12 items of 10 systemic involvements. Question about headache, oral ulcers, genital ulcers, erythema, skin pustules, joints (arthralgia), joints (athritis), nausea/vomiting/abdominal pain, diarrhea with altered/frank blood per rectum, eye involvement, nervous system involvement, major vessel involvement are scored from 0 or 1 depending on the symptoms of previous 4 weeks by a physician. The total score possible is 12.
Time Frame
Week 12 and Week 24
Title
Change from baseline in simplified electronic medical record -based activity index (EMRAI).
Description
The EMRAI contains nine symptom scoring items and two laboratory results. Items include oral and genital ulcers, ocular symptoms, skin lesions, epididymitis, and symptoms related to the involvement of joints, the GI tract, the vascular system, and the central nervous system (CNS). laboratory results includ erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP). The presence of each item, ESR and CRP are dichotomised as 0 or 1. The total score possible is 11.
Time Frame
Week 12 and Week 24
Title
Change from baseline in Behcet's disease ocular inflammatory score 24 (BOS24)
Description
Behcet's disease ocular attack score 24 (BOS24) consists of a total 24 points divided into 6 parameters of ocular inflammatory symptoms, including anterior chamber cells (maximum 4 points), vitreous opacity (maximum 4 points), peripheral fundus lesions (maximum 8 points), posterior pole lesions (maximum 4 points), subfoveal lesions (maximum 2 points), and optic disc lesions (maximum 2 points).
Time Frame
Week 12 and Week 24
Title
Change from baseline in erythrocyte sedimentation rate
Description
erythrocyte sedimentation rate
Time Frame
Week 12 and Week 24
Title
Rate of mean change in DAIBD score of 20 or more from baseline.
Description
This primary endpoint applies to intestinal BD patients.The DAIBD will be assessed by collecting information on 8 different intestinal BD-related variables. These 8 variables are: fever, abdominal mass, abdominal tenderness, intestinal complications, extraintestinal manifestations, general well-being, abdominal pain, and total number of liquid stools. The last 3 variables are scored over 7 days by the participant on a diary card. Abdominal pain will be measured using the 11-point numeric rating scale (NRS) to standardize the evaluation of pain and the result of 11-point NRS will be divided into 4 grades (none, mild, moderate, severe) to fill out the DAIBD. where, None indicate 0; Mild indicate 1-3; Moderate indicate 4-6; Severe indicate 7-10.
Time Frame
week12
Title
Rate of equal or more than 20% changes in Visual acuity.
Description
This primary endpoint applies to ocular involvement of BD patients.
Time Frame
week12
Title
Rate of participants without oral and genital ulcers.
Description
Ulcers will be examined by a physician.
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female ≥18 and ≤70 years of age at time of screening;
Diagnosis of Behcet disease defined by the International Study Group Criteria of 1989;
Patients who had active disease activity or intolerance after 3 months of conventional therapy; patients who had relapsed disease activity without treatment. Active manifestations including oral ulcers, genital ulcers, arthralgia, skin lesions and other systemic involvement manifestations. Intestinal BD-associated symptoms (abdominal pain, diarrhea, melena, etc.) and endoscopic evidence of active ulcers in the intestine. Aggravated visual acuity on a Snellen chart in at least one eye. Neurological BD (NBD) is classifies as either acute NBD (ANB) or chronic progressive NBD (CPNB) in accordance with the diagnostic criteria for NBD. Vascular BD (VBD) patients have active vasculitis lesions (deep vein thrombosis, aortic lesions, etc.) and abnormalities in inflammatory markers such as serum C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) at enrollment.
Apply glucocorticoids (≤1.0mg/Kg*d prednisone or equivalent doses of other hormones) for 4 weeks. DMARDs ( methotrexate, hydroxychloroquine, azathioprine, morphine, leflunomide, cyclosporine, mycophenolate mofeti ) need to stable for 4 weeks. Other medications, such as, IVIg and cyclophosphamide need to more than 2 months, Rituximab for 6 months, other biological agents (infliximab, adalimumab, etanercept, anakinra, etc.) for 3 months.
Have given written informed consent and patients are expected to be able to comply with the requirements of the study follow-up plan and other protocols.
Exclusion Criteria:
Stable disease activity;
Received glucocorticoid >1.0mg/Kg*d within 4 weeks, used rituximab within 6 months and other biological agents within 3 months.
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 disease including hematopathy, gastrointestinal disease, endocrinopathy, pulmonary, neuropathy.
Known allergies, hypersensitivity, or intolerance to IL-2 or its excipients.
Severe infection, such as hepatitis, HIV, syphilis, pneumonia, bacteremia, cytomegalovirus and so on.
Malignancy;
Had uncontrolled psychiatric or emotional disorder;
Pregnant or breast-feeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jiali Chen, MD
Phone
+8618801206400
Email
chenjiali0389@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jing He, MD
Phone
8618611707347
Email
hejing1105@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhanguo Li, MD,PhD
Organizational Affiliation
Department of Rheumatology and Immunology, Peking University People's Hospital.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Rheumatology and Immunology, Peking University People's Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiali Chen, MD
Phone
+8618801206400
Email
chenjiali0389@163.com
First Name & Middle Initial & Last Name & Degree
Jing He, MD
Phone
8618611707347
Email
hejing1105@126.com
First Name & Middle Initial & Last Name & Degree
Zhanguo Li, MD,PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23912800
Citation
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.
Results Reference
background
PubMed Identifier
18427720
Citation
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.
Results Reference
background
PubMed Identifier
28524639
Citation
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.
Results Reference
background
PubMed Identifier
28442519
Citation
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.
Results Reference
background
Links:
URL
http://www.clinicaltrials.gov
Description
Primary outcome for BD patients
Learn more about this trial
Low-dose IL-2 Treatment on Behcet's Disease
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