search
Back to results

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

Primary Purpose

Hepatitis C

Status
Unknown status
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Interleukin-7
Sponsored by
Cytheris SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring interleukin-7, immune-based therapies, hepatitis C, chronic hepatitis, resistance to Peg-interferon and ribavirin bi-therapy, immune specific responses to HCV, phase 1/2a, viral disease, liver disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital Jean Verdier
  • Beaujon Hospital
  • Hopital Kremlin Bicêtre
  • Hopital Civil
  • Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi
  • Fatebenefratelli e Oftalmico
  • San Raffaele Scientific Institute
  • University of Zurich

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CYT107

Arm Description

Outcomes

Primary Outcome Measures

To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin

Secondary Outcome Measures

To characterize pharmacokinetics and pharmacodynamics of CYT107
To evaluate in the context of a dose escalation strategy the potential anti-viral effect of CYT107
To evaluate the immune specific response to HCV
To document the long-term safety and viral load variations

Full Information

First Posted
December 2, 2009
Last Updated
October 17, 2012
Sponsor
Cytheris SA
search

1. Study Identification

Unique Protocol Identification Number
NCT01025297
Brief Title
Dose Escalation Study of Interleukin-7 (IL-7) and Bitherapy in HCV Genotype 1 or 4 Patients Resistant to Bitherapy Alone
Acronym
Eclipse 2
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Unknown status
Study Start Date
July 2008 (undefined)
Primary Completion Date
December 2012 (Anticipated)
Study Completion Date
March 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytheris SA

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
Keywords
interleukin-7, immune-based therapies, hepatitis C, chronic hepatitis, resistance to Peg-interferon and ribavirin bi-therapy, immune specific responses to HCV, phase 1/2a, viral disease, liver disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CYT107
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Interleukin-7
Intervention Description
3 dose levels: 3, 10 & 20 µg/kg. 4 administrations, 1 per week
Primary Outcome Measure Information:
Title
To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin
Time Frame
12 weeks after the start of IL-7
Secondary Outcome Measure Information:
Title
To characterize pharmacokinetics and pharmacodynamics of CYT107
Time Frame
12 weeks after the start of IL-7
Title
To evaluate in the context of a dose escalation strategy the potential anti-viral effect of CYT107
Time Frame
12 weeks after the start of IL-7
Title
To evaluate the immune specific response to HCV
Time Frame
12 weeks after the start of IL-7
Title
To document the long-term safety and viral load variations
Time Frame
48 weeks after the start of IL-7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tilman Gerlach
Organizational Affiliation
Hospital of San Gallen-Switzerland
Official's Role
Study Chair
Facility Information:
Facility Name
Hopital Jean Verdier
City
Bondy
Country
France
Facility Name
Beaujon Hospital
City
Clichy
Country
France
Facility Name
Hopital Kremlin Bicêtre
City
Kremlin Bicêtre
Country
France
Facility Name
Hopital Civil
City
Strasbourg
Country
France
Facility Name
Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi
City
Bologna
Country
Italy
Facility Name
Fatebenefratelli e Oftalmico
City
Milano
Country
Italy
Facility Name
San Raffaele Scientific Institute
City
Milano
Country
Italy
Facility Name
University of Zurich
City
Zurich
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs