Dose Escalation of Interleukin-1 (IL-7) Added on Antiviral Treatment and Vaccination in HBeAg-negative Chronic Hepatitis B Virus (HBV) Infected Patients

Study Overview
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Brief Summary
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This study is designed to evaluate the safety of biological active dose of a new experimental drug, IL-7, in combination with anti viral therapy and vaccine in patients with Hepatitis B chronic infection.

Detailed Description
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This is a Phase I/IIa inter-patient dose-escalation study assessing weekly doses of Interleukin-7 (CYT107) in HBeAg-negative chronic hepatitis B infected adult patients. The dose escalation is aimed at establishing the safety of a biologically active doses of CYT107 added to the current antiviral therapy with entecavir or tenofovir and vaccination or not. At each dose level, study patients will receive one subcutaneous administration of CYT107 per week for a total of 4. Groups of 8 patients will be entered at each dose level of CYT107. Three dose levels are planned. At each dose level, patients are randomized between 2 arms of treatment: tritherapy (CYT107, vaccine and antiviral treatment) or bitherapy (CYT107 and vaccine). Each treatment group is composed of 4 patients, 3 receiving experimental treatments, 1 just the current antiviral treatment (control patient). According to the treatment arm, eligible patients initially receive a vaccine if in treatment group of tritherapy, thereafter, CYT107 is added for a cycle of four weekly injections (if not a control patient) at a defined dose level. If in treatment group of tritherapy, patients will receive 2 additional doses of vaccine. The treatment phase for the tritherapy group is from first vaccine D0 to last vaccine W12 and includes CYT107 administration from W4 to W7. The treatment phase for the bitehrapy group is from W4 to W7 corresponding to CYT104 injections. The patients are then followed on a regular basis until reaching 52 weeks after the D0. Participants will have 1 overnight hospitalization and 12 clinic visit on a period of 55 weeks. During the visits the following may be done: medical history, physical examination, blood tests electrocardiograms (ECG) chest X-Ray liver/spleen imaging urine tests

Official Title
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A Phase Randomized Open Labelled Controlled Dose Escalation Study of Repeated Administration of CYT107 (Glyco-r-hIL-7) Added on Antiviral Treatment and Vaccination in HBeAg-negative Chronic Hepatitis B-infected Patients

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: CYT107+GenHevac+entecavir or tenofovir
* Drug: CYT107+ entecavir or tenofovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HBV-infected patients HBeAg-negative patients Age > 18 years Patients with active chronic hepatitis at the start of the antiviral treatment Patient with a HBV DNA undetectable (<70 copies/ml) stable for at least 3 months under entecavir or tenofovir treatment. Ongoing treatment by entecavir or tenofovir at screening Note: previous treatment with pegylated IFN monotherapy, before the start of entecavir or tenofovir, is acceptable Exclusion Criteria: Infection by HCV Infection by HIV-1 and /or HIV-2 Apart from HBV infection, presence of active infection requiring a specific treatment or a hospitalization Previous treatment by lamivudine and/or nucleosides analogues Inactive carrier Cirrhosis Other liver disease (notably from alcoholic, metabolic or immunological origin) History of clinical autoimmune disease or active auto-immune disease Type I diabetes mellitus Severe asthma, presently on chronic medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tritherapy: CYT107+ vaccine+ antiviral<br> | Drug: CYT107+GenHevac+entecavir or tenofovir<br>* 4 patients per arm for each dose level. 3 patients receiving experimental treatment (CYT107 and vaccine) in addition to current antiviral treatment and 1 control patient only the current antiviral treatment<br>|
| Experimental: Bitherapy: CYT107 + antiviral<br> | Drug: CYT107+ entecavir or tenofovir<br>* 4 patients per arm for each dose level. 3 patients receiving experimental treatment (CYT107) in addition to current antiviral treatment and 1 control patient only the current antiviral treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the short and long-term safety and biological activity of CYT107 in patients with a HBeAg-negative chronic hepatitis B who have, at screening a HBV DNA undetectable stable for at least 3 months with antiviral treatment. |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the pharmacokinetics and pharmacodynamics of CYT107 in humans chronically infected with HBV. |  | Week 12 | 
| To assess the effects of the tri-therapy (CYT107 + HBV vaccine + antiviral treatment) versus bi-therapy (CYT107 + antiviral treatment) versus control (antiviral treatment) on the markers of the HBV infection (antiviral activity)at W16 weeks and W52 |  | Week 12 and Week 52 | 
| To quantify the effects of the tri-therapy (CYT107 + HBV vaccine + antiviral treatment) versus bi-therapy (CYT107 + antiviral treatment) versus control (antiviral treatment) on the immune system at W16 weeks |  | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interleukin-7, immune-based therapies, hepatitis B, HBe negative, HBV vaccination, entecavir, tenofovir, chronic hepatitis, immune specific responses to HBV, phase 1/2a, viral disease, liver disease