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

Sponsor

Cytheris SA (Industry)

Overall Status

Unknown status

CT.gov ID

NCT01025297

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Interleukin-7	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jul 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Mar 1, 2013

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: CYT107

Drug: Interleukin-7

3 dose levels: 3, 10 & 20 µg/kg. 4 administrations, 1 per week

Outcome Measures

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 [12 weeks after the start of IL-7]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country
1	Hopital Jean Verdier	Bondy	France
2	Beaujon Hospital	Clichy	France
3	Hopital Kremlin Bicêtre	Kremlin Bicêtre	France
4	Hopital Civil	Strasbourg	France
5	Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi	Bologna	Italy
6	Fatebenefratelli e Oftalmico	Milano	Italy
7	San Raffaele Scientific Institute	Milano	Italy
8	University of Zurich	Zurich	Switzerland