Cytomegalovirus InfectionsPhase 1/2NCT04225780
Treatment of Low Dose IL-2 and Ganciclovir in Cytomegalovirus Infection
A Phase 1/2 study testing Low-dose IL-2 and ganciclovir in people with Cytomegalovirus Infections, run by Peking University People's Hospital.
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- Low-dose IL-2 and ganciclovir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2020to 30 Mar 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Rheumatic disease by the Criteria ;
- Patients have current CMV infection, CMV-DNA are positive.
- Apply corticosteroid less than 1.0mg/kg/d.
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read the 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
- Being tested
- Low-dose IL-2 and ganciclovir
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose IL-2 and ganciclovirDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment of low-dose IL-2 and ganciclovir | Experimental | 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. Receives: Drug: Low-dose IL-2 and ganciclovir |
| Treatment of ganciclovir | Placebo comparator | If patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in ganciclovir treatment group. Receives: Drug: Low-dose IL-2 and ganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline of NK cells cytotoxicity after treatment
NK cells cytotoxicity will be detected by flow cytometry
Measured: Days 7 after treatment
Secondary outcomes (6)
The total dose for anti-viral drugs.
The total dose of ganciclovir
Measured: Day for drug withdrawal.
The change of cytokine after low-dose IL-2 treatment.
Detect by flow cytometry and ELISA.
Measured: Day after anti-viral treatment and 3 months.
The change of NK cell subsets.
Detect by flow cytometry.
Measured: Day after anti-viral treatment and 3 months.
The change of level of CMV immunoglobulin M (IgM)
Detect by EILSA.
Measured: Day for drug withdrawal and 3 months.
The change of level of CMV immunoglobulin G (IgG)
Detect by EILSA.
Measured: Day for drug withdrawal and 3 months.
The day for CMV infection patients convert into negative.
CMV-DNA will be detected by PCR
Measured: Days when CMV-DNA are less than 10^3 copies.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start1 Feb 2020 (estimated)
- Primary completion31 Dec 2020 (estimated)
- Study completion30 Mar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by Peking University People's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zhanguo Li, PhD MD, Principal investigator, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04225780
- Sponsor's protocol ID
- TLDIGCI
- Status last verified
- Jan 2020
- First submitted
- 9 Jan 2020
- Last updated
- 13 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31537547
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04225780
- Acronym / sponsor ID
- TLDIGCI
- Conditions
- Cytomegalovirus Infections
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Peking University People's HospitalUniversity, hospital or other
- Study start
- 1 Feb 2020 (estimated)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 30 Mar 2021 (estimated)
- First posted
- 13 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Treatment of low-dose IL-2 and ganciclovir | Experimental | Drug: Low-dose IL-2 and ganciclovirIf 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. |
| Treatment of ganciclovir | Placebo comparator | Drug: Low-dose IL-2 and ganciclovirIf patients are eligible, which CMV-DNA are more than 10^3 copies, it will be randomly distributed in ganciclovir treatment group. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of Rheumatic disease by the Criteria ;
- Patients have current CMV infection, CMV-DNA are positive.
- Apply corticosteroid less than 1.0mg/kg/d.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-dose IL-2 and ganciclovirIf 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. | Drug | Treatment of ganciclovir, Treatment of low-dose IL-2 and ganciclovir |
Primary outcome
Change from baseline of NK cells cytotoxicity after treatment
Time frame: Days 7 after treatment
NK cells cytotoxicity will be detected by flow cytometry
6 secondary outcomes
The total dose for anti-viral drugs.
Time frame: Day for drug withdrawal.
The change of cytokine after low-dose IL-2 treatment.
Time frame: Day after anti-viral treatment and 3 months.
The change of NK cell subsets.
Time frame: Day after anti-viral treatment and 3 months.
The change of level of CMV immunoglobulin M (IgM)
Time frame: Day for drug withdrawal and 3 months.
The change of level of CMV immunoglobulin G (IgG)
Time frame: Day for drug withdrawal and 3 months.
The day for CMV infection patients convert into negative.
Time frame: Days when CMV-DNA are less than 10^3 copies.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Background: PubMed 31537547He 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.
- clinicaltrials.govLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhanguo Li, PhD MD principal investigator
Peking University People's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Low-dose IL-2 and ganciclovir in people with Cytomegalovirus Infections, run by Peking University People's Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jiali Chen, MD (+8618801206400, chenjiali0389@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of NK cells cytotoxicity after treatment (time frame: Days 7 after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04225780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.