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

Hepatitis C Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01025297
• Other study ID #: CLI-107-07
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: December 2, 2009
• Last updated: October 17, 2012
• Start date: July 2008
• Est. completion date: March 2013

Study information

• Verified date: October 2012
• Source: Cytheris SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• Interleukin-7
3 dose levels: 3, 10 & 20 µg/kg. 4 administrations, 1 per week

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cytheris SA

Countries where clinical trial is conducted

France,  Italy,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	To characterize pharmacokinetics and pharmacodynamics of CYT107		12 weeks after the start of IL-7	No
Secondary	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	No
Secondary	To evaluate the immune specific response to HCV		12 weeks after the start of IL-7	No
Secondary	To document the long-term safety and viral load variations		48 weeks after the start of IL-7	Yes