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

Phase 1

• Conditions: Chronic Hepatitis B
• Interventions: Drug: CYT107+ entecavir or tenofovir; Drug: CYT107+GenHevac+entecavir or tenofovir

• Registration Number: NCT01027065
• Lead Sponsor: Cytheris SA

Brief Summary

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

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

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2009-12-04
• Study First Submitted QC: 2009-12-04
• Study First Posted: 2009-12-07
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-17
• Last Update Posted: 2012-10-18
• Primary Completion: 2012-11
• Study Completion: 2013-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bitherapy: CYT107 + antiviral	CYT107+ entecavir or tenofovir	-
Tritherapy: CYT107+ vaccine+ antiviral	CYT107+GenHevac+entecavir or tenofovir	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (8)

Hopital Michallon; 🇫🇷 Grenoble, France

Hopital Henri Mendor-Service d'HepatoGastroEnterologie; 🇫🇷 Creteil, France

Hopital de l'Hotel Dieu; 🇫🇷 Lyon, France

Hopital Civil; 🇫🇷 Strasbourg, France

Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi; 🇮🇹 Bologna, Italy

Hopital Saint Joseph; 🇫🇷 Marseille, France

Hopital Tenon; 🇫🇷 Paris, France

CHU l'Archet; 🇫🇷 Nice, France