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

• ClinicalTrials.gov Identifier: NCT01027065
• Recruitment Status: Unknown
• First Posted: December 7, 2009
• Last Update Posted: October 18, 2012
• Sponsor: Cytheris SA
• Information provided by (Responsible Party): Cytheris SA

Tracking Information

• First Submitted Date: December 4, 2009
• First Posted Date: December 7, 2009
• Last Update Posted Date: October 18, 2012
• Study Start Date: December 2009
• Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 4, 2009): 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. [ Time Frame: Week 12 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 4, 2009)

• To characterize the pharmacokinetics and pharmacodynamics of CYT107 in humans chronically infected with HBV. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 16 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Hepatitis B

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
• Drug: 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

Study Arms

• Experimental: Tritherapy: CYT107+ vaccine+ antiviral
  Intervention: Drug: CYT107+GenHevac+entecavir or tenofovir
• Experimental: Bitherapy: CYT107 + antiviral
  Intervention: Drug: CYT107+ entecavir or tenofovir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 4, 2009): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2013
• Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Italy

Administrative Information

• NCT Number: NCT01027065
• Other Study ID Numbers: CLI-107-10; 2009-010709-35 ( Other Identifier: EUDRACT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Cytheris SA
• Original Responsible Party: Michel MORRE, Cytheris
• Current Study Sponsor: Cytheris SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Christophe Hezode; Hopital Henri Mondor-Créteil-France
• Principal Investigator: Pietro Andreone; S. Orsola Malpighi- Bologna-Italy

• PRS Account: Cytheris SA
• Verification Date: October 2012