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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Cytheris SA
ClinicalTrials.gov Identifier:
NCT01027065
First received: December 4, 2009
Last updated: October 17, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis B
Drug: CYT107+GenHevac+entecavir or tenofovir
Drug: CYT107+ entecavir or tenofovir
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Cytheris SA:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To characterize the pharmacokinetics and pharmacodynamics of CYT107 in humans chronically infected with HBV. [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: December 2009
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tritherapy: CYT107+ vaccine+ antiviral 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
Experimental: Bitherapy: CYT107 + antiviral 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01027065

Locations
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, France
Italy
Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi
Bologna, Italy
Sponsors and Collaborators
Cytheris SA
Investigators
Study Chair: Christophe Hezode Hopital Henri Mondor-Créteil-France
Principal Investigator: Pietro Andreone S. Orsola Malpighi- Bologna-Italy
  More Information

No publications provided

Responsible Party: Cytheris SA
ClinicalTrials.gov Identifier: NCT01027065     History of Changes
Other Study ID Numbers: CLI-107-10, 2009-010709-35
Study First Received: December 4, 2009
Last Updated: October 17, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency

Keywords provided by Cytheris SA:
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

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Antiviral Agents
Tenofovir
Tenofovir disoproxil
Entecavir
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 28, 2014