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

Chronic Hepatitis B Clinical Trial

— CONVERT  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01027065
• Other study ID #: CLI-107-10
• Secondary ID: 2009-010709-35
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: December 4, 2009
• Last updated: October 17, 2012
• Start date: December 2009
• Est. completion date: March 2013

Study information

• Verified date: October 2012
• Source: Cytheris SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: March 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• CYT107+GenHevac+entecavir or tenofovir
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
• CYT107+ entecavir or tenofovir
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

Locations

Country	Name	City	State
France	Hopital Henri Mendor-Service d'HepatoGastroEnterologie	Creteil
France	Hopital Michallon	Grenoble
France	Hopital de l'Hotel Dieu	Lyon
France	Hopital Saint Joseph	Marseille
France	CHU l'Archet	Nice
France	Hopital Tenon	Paris
France	Hopital Civil	Strasbourg
Italy	Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
Cytheris SA

Countries where clinical trial is conducted

France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	To characterize the pharmacokinetics and pharmacodynamics of CYT107 in humans chronically infected with HBV.		Week 12	No
Secondary	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	No
Secondary	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	No