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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Cytheris SA
ClinicalTrials.gov Identifier:
NCT01025297
First received: December 2, 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 standard bi-therapy in patients with Hepatitis C chronic infection identified as non responders to the standard bi-therapy alone.


Condition Intervention Phase
Hepatitis C
Drug: Interleukin-7
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Cytheris SA:

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 [ Time Frame: 12 weeks after the start of IL-7 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To characterize pharmacokinetics and pharmacodynamics of CYT107 [ Time Frame: 12 weeks after the start of IL-7 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate the immune specific response to HCV [ Time Frame: 12 weeks after the start of IL-7 ] [ Designated as safety issue: No ]
  • To document the long-term safety and viral load variations [ Time Frame: 48 weeks after the start of IL-7 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: July 2008
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CYT107 Drug: Interleukin-7
3 dose levels: 3, 10 & 20 µg/kg. 4 administrations, 1 per week

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01025297

Locations
France
Hopital Jean Verdier
Bondy, France
Beaujon Hospital
Clichy, France
Hopital Kremlin Bicêtre
Kremlin Bicêtre, France
Hopital Civil
Strasbourg, France
Italy
Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi
Bologna, Italy
San Raffaele Scientific Institute
Milano, Italy
Fatebenefratelli e Oftalmico
Milano, Italy
Switzerland
University of Zurich
Zurich, Switzerland
Sponsors and Collaborators
Cytheris SA
Investigators
Study Chair: Tilman Gerlach Hospital of San Gallen-Switzerland
  More Information

No publications provided

Responsible Party: Cytheris SA
ClinicalTrials.gov Identifier: NCT01025297     History of Changes
Other Study ID Numbers: CLI-107-07
Study First Received: December 2, 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 C
chronic hepatitis
resistance to Peg-interferon and ribavirin bi-therapy
immune specific responses to HCV
phase 1/2a
viral disease
liver disease

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on August 18, 2014