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

Cytheris

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Chronic Hepatitis B

Treatments

Drug: CYT107+ entecavir or tenofovir

Drug: CYT107+GenHevac+entecavir or tenofovir

Study type

Interventional

Funder types

Industry

Identifiers

NCT01027065

CLI-107-10

2009-010709-35 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

Enrollment

24 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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