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

Phase 1

• Conditions: Hepatitis C
• Interventions: Drug: Interleukin-7

• Registration Number: NCT01025297
• Lead Sponsor: Cytheris SA

Brief Summary

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.

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 Timeline

• Study Start: 2008-07
• Study First Submitted: 2009-12-02
• Study First Submitted QC: 2009-12-02
• Study First Posted: 2009-12-03
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-17
• Last Update Posted: 2012-10-18
• Primary Completion: 2012-12
• Study Completion: 2013-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CYT107	Interleukin-7	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (8)

University of Zurich; 🇨🇭 Zurich, Switzerland

Hopital Jean Verdier; 🇫🇷 Bondy, France

San Raffaele Scientific Institute; 🇮🇹 Milano, Italy

Fatebenefratelli e Oftalmico; 🇮🇹 Milano, Italy

Beaujon Hospital; 🇫🇷 Clichy, France

Hopital Kremlin Bicêtre; 🇫🇷 Kremlin Bicêtre, France

Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi; 🇮🇹 Bologna, Italy

Hopital Civil; 🇫🇷 Strasbourg, France