Clinical trial NCT01025297: Dose Escalation Study of Interleukin-7 (IL-7) and Bitherapy in HCV Genotype 1 or 4 Patients Resistant to Bitherapy Alone
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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Cytheris SA
Sponsor class: INDUSTRY
First posted: 2009-12-03
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: To evaluate at W 12 the safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin
timeFrame: 12 weeks after the start of IL-7
Secondary outcomes:
measure: To characterize pharmacokinetics and pharmacodynamics of CYT107
timeFrame: 12 weeks after the start of IL-7
measure: To evaluate in the context of a dose escalation strategy the potential anti-viral effect of CYT107
timeFrame: 12 weeks after the start of IL-7
measure: To evaluate the immune specific response to HCV
timeFrame: 12 weeks after the start of IL-7
measure: To document the long-term safety and viral load variations
timeFrame: 48 weeks after the start of IL-7
Other outcomes:
Locations:
city: Bondy
country: France
facility: Hopital Jean Verdier
city: Clichy
country: France
facility: Beaujon Hospital
city: Kremlin Bicêtre
country: France
facility: Hopital Kremlin Bicêtre
city: Strasbourg
country: France
facility: Hopital Civil
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola Malpighi
city: Milano
country: Italy
facility: Fatebenefratelli e Oftalmico
city: Milano
country: Italy
facility: San Raffaele Scientific Institute
city: Zurich
country: Switzerland
facility: University of Zurich
Study officials:
affiliation: Hospital of San Gallen-Switzerland
name: Tilman Gerlach
role: STUDY_CHAIR
References: