Treatment of Low Dose IL-2 and Ganciclovir in Cytomegalovirus Infection

Cytomegalovirus Infections Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04225780
• Other study ID #: TLDIGCI
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: February 1, 2020
• Est. completion date: March 30, 2021

Study information

• Verified date: January 2020
• Source: Peking University People's Hospital
• Contact: Jiali Chen, MD
• Phone: +8618801206400
• Email: chenjiali0389[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: March 30, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Infection

Intervention

Drug:
• Low-dose IL-2 and ganciclovir
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of NK cells cytotoxicity after treatment	NK cells cytotoxicity will be detected by flow cytometry	Days 7 after treatment
Secondary	The total dose for anti-viral drugs.	The total dose of ganciclovir	Day for drug withdrawal.
Secondary	The change of cytokine after low-dose IL-2 treatment.	Detect by flow cytometry and ELISA.	Day after anti-viral treatment and 3 months.
Secondary	The change of NK cell subsets.	Detect by flow cytometry.	Day after anti-viral treatment and 3 months.
Secondary	The change of level of CMV immunoglobulin M (IgM)	Detect by EILSA.	Day for drug withdrawal and 3 months.
Secondary	The change of level of CMV immunoglobulin G (IgG)	Detect by EILSA.	Day for drug withdrawal and 3 months.
Secondary	The day for CMV infection patients convert into negative.	CMV-DNA will be detected by PCR	Days when CMV-DNA are less than 10^3 copies.

External Links

•   clinicaltrials.gov