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

NCT ID: NCT04225780

Last Updated: 2020-01-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2021-03-30

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.

Conditions

Cytomegalovirus Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment of 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 and low-dose IL-2 is defined as 1 million IU per day subcutaneously.

Group Type: EXPERIMENTAL

Low-dose IL-2 and ganciclovir

Intervention Type: DRUG

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.

Treatment of ganciclovir

If patients are eligible, which CMV-DNA are more than 10\^3 copies, it will be randomly distributed in ganciclovir treatment group.

Group Type: PLACEBO_COMPARATOR

Low-dose IL-2 and ganciclovir

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhanguo Li, PhD MD

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Central Contacts

Jiali Chen, MD

Role: CONTACT

chenjiali0389@163.com

+8618801206400

Zhanguo Li, PhD MD

Role: CONTACT

zgli99@aliyun.com

+088324317

References

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.

Reference Type: BACKGROUND

PMID: 31537547 (View on PubMed)

Related Links

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

clinicaltrials.gov

Other Identifiers

TLDIGCI

Identifier Type: -

Identifier Source: org_study_id