Clinical trial NCT01027065: Dose Escalation of Interleukin-1 (IL-7) Added on Antiviral Treatment and Vaccination in HBeAg-negative Chronic Hepatitis B Virus (HBV) Infected Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Chronic Hepatitis B
Keywords: 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
Lead sponsor: Cytheris SA
Sponsor class: INDUSTRY
First posted: 2009-12-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Week 12
Secondary outcomes:
measure: To characterize the pharmacokinetics and pharmacodynamics of CYT107 in humans chronically infected with HBV.
timeFrame: Week 12
measure: 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
timeFrame: Week 12 and Week 52
measure: 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
timeFrame: Week 16
Other outcomes:
Locations:
city: Creteil
country: France
facility: Hopital Henri Mendor-Service d'HepatoGastroEnterologie
city: Grenoble
country: France
facility: Hopital Michallon
city: Lyon
country: France
facility: Hopital de l'Hotel Dieu
city: Marseille
country: France
facility: Hopital Saint Joseph
city: Nice
country: France
facility: CHU l'Archet
city: Paris
country: France
facility: Hopital Tenon
city: Strasbourg
country: France
facility: Hopital Civil
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi
Study officials:
affiliation: Hopital Henri Mondor-Créteil-France
name: Christophe Hezode
role: STUDY_CHAIR
affiliation: S. Orsola Malpighi- Bologna-Italy
name: Pietro Andreone
role: PRINCIPAL_INVESTIGATOR
References: