Treatment of Low Dose IL-2 and Ganciclovir in Cytomegalovirus Infection
Primary Purpose
Cytomegalovirus Infections
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Low-dose IL-2 and ganciclovir
Sponsored by
About this trial
This is an interventional treatment trial for Cytomegalovirus Infections
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of Rheumatic disease by the Criteria ;
- Patients have current CMV infection, CMV-DNA are positive.
- Apply corticosteroid less than 1.0mg/kg/d.
Exclusion Criteria:
- CMV-DNA is negative.
- Other infection, such as bacteremia, hepatitis B and C viruses, HIV, syphilis, bacteremia, Epstein-Barr virus and so on.
- Known allergies, hypersensitivity, or intolerance to IL-2 or its excipients.
- Severe comorbidities: including 1) Heart failure (≥ grade III NYHA); 2) Renal insufficiency (creatinine clearance ≤30 ml/min); 3) Hepatic insufficiency (serum ALT or AST >3 times the ULN, or total bilirubin >ULN for the central laboratory conducting the test); 4) Other disease including hematopathy, gastrointestinal disease, endocrinopathy, pulmonary, neuropathy.
- Malignancy.
- Had uncontrolled psychiatric or emotional disorder.
- Pregnant or breast-feeding
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment of low-dose IL-2 and ganciclovir
Treatment of ganciclovir
Arm Description
If patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in low-dose IL-2 and ganciclovir group and low-dose IL-2 is defined as 1 million IU per day subcutaneously.
If patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in ganciclovir treatment group.
Outcomes
Primary Outcome Measures
Change from baseline of NK cells cytotoxicity after treatment
NK cells cytotoxicity will be detected by flow cytometry
Secondary Outcome Measures
The total dose for anti-viral drugs.
The total dose of ganciclovir
The change of cytokine after low-dose IL-2 treatment.
Detect by flow cytometry and ELISA.
The change of NK cell subsets.
Detect by flow cytometry.
The change of level of CMV immunoglobulin M (IgM)
Detect by EILSA.
The change of level of CMV immunoglobulin G (IgG)
Detect by EILSA.
The day for CMV infection patients convert into negative.
CMV-DNA will be detected by PCR
Full Information
NCT ID
NCT04225780
First Posted
January 9, 2020
Last Updated
January 9, 2020
Sponsor
Peking University People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04225780
Brief Title
Treatment of Low Dose IL-2 and Ganciclovir in Cytomegalovirus Infection
Official Title
The Efficiency and Safety of Low Dose IL-2 and Ganciclovir in Treatment of Cytomegalovirus Infection: an Open Label, Prospective and Control Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2020 (Anticipated)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
March 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
No
5. Study Description
Brief Summary
Cytomegalovirus (CMV) infections is a severe infection in patients of rheumatic disease treated with corticosteroid and immunosuppressive agents. Ganciclovir is the main therapy in CMV infection, accompanied with diverse side effects, including neutropenia, anemia, disorder of renal function and so on, which are also common symptoms of rheumatic diseases. Additionally, prolonged antiviral treatment may delay recovery of virus, specific immune responses, resulting in an increasing of late-onset CMV disease.
IL-2 is a pleotropic cytokine which can promote the proliferation and function of CD8+ T cells and NK cells through the combination with IL-2 receptor. Recently, several studies have revealed that low dose IL-2 is an effective and safe therapy for autoimmune disease. In systemic lupus erythematous patients, additionally, patients treated with low-dose IL-2 had lower incidence of infection with increased percentages of natural killer (NK) cells.
In this prospective clinical trial, we propose to assess the effective and safety of low-dose IL-2 combined with ganciclovir in the treatment of CMV infection. Meanwhile, we will assess the immune response of after IL-2 treatment.
Detailed Description
In rheumatic diseases, CMV infection are more frequent in patients after corticosteroid pulse treatment and long-term treatment of corticosteroid and immunosuppressor.
If patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in low-dose IL-2 and ganciclovir group, or ganciclovir group. Low-dose IL-2 is defined as 1 million IU per day subcutaneously, The CMV-DNA levels will be monitored until it turned out to be negative. In this period, we will simultaneously monitor the immune response in regard to CMV infection, including innate immune response, such as IFN-γ, TNF-α, natural killer cells, and adaptive immune response, such as CMV specific CD8+ T cells, T helper cells and so on.
We will follow these patients for at least 3 months after drug withdrawal. If patient belonging to any of these two groups develops a viral infection, then the patient will receive treatment with ganciclovir.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
We distribute the patients with CMV infection into two groups, one group will be treated with low-dose IL-2 and ganciclovir, another group will be only treated with ganciclovir.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment of low-dose IL-2 and ganciclovir
Arm Type
Experimental
Arm Description
If patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in low-dose IL-2 and ganciclovir group and low-dose IL-2 is defined as 1 million IU per day subcutaneously.
Arm Title
Treatment of ganciclovir
Arm Type
Placebo Comparator
Arm Description
If patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in ganciclovir treatment group.
Intervention Type
Drug
Intervention Name(s)
Low-dose IL-2 and ganciclovir
Intervention Description
If patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in low-dose IL-2 and ganciclovir group, or ganciclovir group. Low-dose IL-2 is defined as 1 million IU per day subcutaneously.
Primary Outcome Measure Information:
Title
Change from baseline of NK cells cytotoxicity after treatment
Description
NK cells cytotoxicity will be detected by flow cytometry
Time Frame
Days 7 after treatment
Secondary Outcome Measure Information:
Title
The total dose for anti-viral drugs.
Description
The total dose of ganciclovir
Time Frame
Day for drug withdrawal.
Title
The change of cytokine after low-dose IL-2 treatment.
Description
Detect by flow cytometry and ELISA.
Time Frame
Day after anti-viral treatment and 3 months.
Title
The change of NK cell subsets.
Description
Detect by flow cytometry.
Time Frame
Day after anti-viral treatment and 3 months.
Title
The change of level of CMV immunoglobulin M (IgM)
Description
Detect by EILSA.
Time Frame
Day for drug withdrawal and 3 months.
Title
The change of level of CMV immunoglobulin G (IgG)
Description
Detect by EILSA.
Time Frame
Day for drug withdrawal and 3 months.
Title
The day for CMV infection patients convert into negative.
Description
CMV-DNA will be detected by PCR
Time Frame
Days when CMV-DNA are less than 10^3 copies.
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:
Diagnosis of Rheumatic disease by the Criteria ;
Patients have current CMV infection, CMV-DNA are positive.
Apply corticosteroid less than 1.0mg/kg/d.
Exclusion Criteria:
CMV-DNA is negative.
Other infection, such as bacteremia, hepatitis B and C viruses, HIV, syphilis, bacteremia, Epstein-Barr virus and so on.
Known allergies, hypersensitivity, or intolerance to IL-2 or its excipients.
Severe comorbidities: including 1) Heart failure (≥ grade III NYHA); 2) Renal insufficiency (creatinine clearance ≤30 ml/min); 3) Hepatic insufficiency (serum ALT or AST >3 times the ULN, or total bilirubin >ULN for the central laboratory conducting the test); 4) Other disease including hematopathy, gastrointestinal disease, endocrinopathy, pulmonary, neuropathy.
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
Zhanguo Li, PhD MD
Phone
+088324317
Email
zgli99@aliyun.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhanguo Li, PhD MD
Organizational Affiliation
Peking University People's Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31537547
Citation
He J, Zhang R, Shao M, Zhao X, Miao M, Chen J, Liu J, Zhang X, Zhang X, Jin Y, Wang Y, Zhang S, Zhu L, Jacob A, Jia R, You X, Li X, Li C, Zhou Y, Yang Y, Ye H, Liu Y, Su Y, Shen N, Alexander J, Guo J, Ambrus J, Lin X, Yu D, Sun X, Li Z. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2020 Jan;79(1):141-149. doi: 10.1136/annrheumdis-2019-215396. Epub 2019 Sep 19.
Results Reference
background
Links:
URL
https://www.clinicaltrials.gov/ct2/show/NCT02985775?id=NCT02505568+OR+NCT02756650+OR+NCT01960790+OR+NCT02648581+OR+NCT02985775+OR+NCT04056533+OR+NCT01185223&draw=2&rank=2&load=cart
Description
clinicaltrials.gov
Learn more about this trial
Treatment of Low Dose IL-2 and Ganciclovir in Cytomegalovirus Infection
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