Clinical trial NCT04225780: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cytomegalovirus Infections
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2020-01-13
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Rheumatic disease by the Criteria ;
2. Patients have current CMV infection, CMV-DNA are positive.
3. Apply corticosteroid less than 1.0mg/kg/d.

Exclusion Criteria:

1. CMV-DNA is negative.
2. Other infection, such as bacteremia, hepatitis B and C viruses, HIV, syphilis, bacteremia, Epstein-Barr virus and so on.
3. Known allergies, hypersensitivity, or intolerance to IL-2 or its excipients.
4. 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.
5. Malignancy.
6. Had uncontrolled psychiatric or emotional disorder.
7. Pregnant or breast-feeding

Primary outcomes:
measure: Change from baseline of NK cells cytotoxicity after treatment
timeFrame: Days 7 after treatment
Secondary outcomes:
measure: The total dose for anti-viral drugs.
timeFrame: Day for drug withdrawal.
measure: The change of cytokine after low-dose IL-2 treatment.
timeFrame: Day after anti-viral treatment and 3 months.
measure: The change of NK cell subsets.
timeFrame: Day after anti-viral treatment and 3 months.
measure: The change of level of CMV immunoglobulin M (IgM)
timeFrame: Day for drug withdrawal and 3 months.
measure: The change of level of CMV immunoglobulin G (IgG)
timeFrame: Day for drug withdrawal and 3 months.
measure: The day for CMV infection patients convert into negative.
timeFrame: Days when CMV-DNA are less than 10^3 copies.
Other outcomes:
Locations:
Study officials:
affiliation: Peking University People's Hospital
name: Zhanguo Li, PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
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.