Dose Escalation Study of Interleukin-7 (IL-7) and Bitherapy in HCV Genotype 1 or 4 Patients Resistant to Bitherapy Alone (Eclipse 2)

A Phase I/IIa Dose Escalation Study of Repeated Administration of "CYT107" (Glyco-r-hIL-7) Add-On Treatment in Genotype 1 or 4 Hcv Infected Patients Resistant to Pegylated Interferon-Alpha and Ribavirin

This study is designed to evaluate the safety of biological active dose of a new experimental drug, IL-7, in combination with standard bi-therapy in patients with Hepatitis C chronic infection identified as non responders to the standard bi-therapy alone.

Study Overview

• Status: Unknown
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Interleukin-7

Detailed Description

This is a Phase I/IIa inter-patient dose-escalation study assessing weekly doses of Interleukin-7 (CYT107) in adult patients infected by virus genotype 1 or 4 of Hepatitis C and resistant to standard treatment with Peg-Interferon and Ribavirin (bitherapy).

The dose escalation is aimed at establishing the safety of a biologically active doses of CYT107 added to the combination therapy of pegylated interferon-alpha and ribavirin. At each dose level, study patients will receive one subcutaneous administration of CYT107 per week for a total of 4.

Groups of 6 patients will be entered at each dose level of CYT107. Three dose levels are planned.

Eligible patients initially receive bi-therapy for 6-10 weeks. Thereafter, CYT107 is added for a cycle of four weekly injections at a defined dose level while standard bi-therapy continues for 9 weeks after CYT107 treatment discontinuation. The patients are then followed on a regular basis until reaching 48 weeks after the CYT107 treatment. The duration of study is approximatively 60 weeks with 20-25 weeks of bi-therapy.

Participants will have 1 overnight hospitalization and 15 clinic visit on a period of 60 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
• Enrollment (Anticipated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bondy, France
    • Hôpital Jean Verdier
  • Clichy, France
    • Beaujon Hospital
  • Kremlin Bicêtre, France
    • Hôpital Kremlin Bicetre
  • Strasbourg, France
    • Hopital Civil
• Italy
  • Bologna, Italy
    • Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi
  • Milano, Italy
    • San Raffaele Scientific Institute
  • Milano, Italy
    • Fatebenefratelli e Oftalmico
• Switzerland
  • Zurich, Switzerland
    • University of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Genotype 1 or 4 infected patients
• Age > 18 years

• Absence of viral response to previous treatments with pegylated interferon-alpha plus ribavirin defined as:

  • Absence of early viral response (EVR) with detectable HCV and with a decrease HCV RNA load < 2 logs, measured by a quantitative PCR tests after 12 weeks of treatment, as compared to baseline levels measured by a similar technique; or
  • Absence of end of treatment response defined by detectable HCV RNA at the end of treatment (24 weeks or 48 weeks)
• Metavir ≤ F3 assessed by biopsy in the last 12 months or by fibroscan if Fibroscan® result < 10 kPa in the last 6 months (biopsy can be avoided)

Exclusion Criteria:

• Active infection by HBV (positive HBs Ag or positive anti HBc antibodies with a detectable HBV DNA viral load).
• Infection by HIV-1 and /or HIV-2
• Apart from HCV infection, presence of active infection requiring a specific treatment or a hospitalization
• Other liver disease (notably from alcoholic, metabolic or immunological origin)
• Body mass index (BMI) > 30kg/m2
• Relapse after previous response to pegylated IFN alpha and ribavirin therapy
• Any history of malignancy apart from curatively treated basal cell carcinoma or in situ cervical carcinoma
• History of clinical autoimmune disease or active auto-immune disease
• History of severe asthma, presently on chronic medications
• Significant cardiac or pulmonary disease
• Prior solid organ or hematopoietic cell transplantation
• Dialyzed patient
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYT107	Drug: Interleukin-7; 3 dose levels: 3, 10 & 20 µg/kg. 4 administrations, 1 per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin	12 weeks after the start of IL-7

Secondary Outcome Measures

Outcome Measure	Time Frame
To characterize pharmacokinetics and pharmacodynamics of CYT107	12 weeks after the start of IL-7
To evaluate in the context of a dose escalation strategy the potential anti-viral effect of CYT107	12 weeks after the start of IL-7
To evaluate the immune specific response to HCV	12 weeks after the start of IL-7
To document the long-term safety and viral load variations	48 weeks after the start of IL-7

Collaborators and Investigators

• Sponsor: Cytheris SA
• Investigators: Study Chair: Tilman Gerlach, Hospital of San Gallen-Switzerland

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): March 1, 2013

Study Registration Dates

• First Submitted: December 2, 2009
• First Submitted That Met QC Criteria: December 2, 2009
• First Posted (Estimate): December 3, 2009

Study Record Updates

• Last Update Posted (Estimate): October 18, 2012
• Last Update Submitted That Met QC Criteria: October 17, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: hepatitis C; liver disease; interleukin-7; chronic hepatitis; viral disease; immune-based therapies; phase 1/2a; resistance to Peg-interferon and ribavirin bi-therapy; immune specific responses to HCV
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C
• Other Study ID Numbers: CLI-107-07