Clinical trial NCT01025596: Dose Escalation Study of IL-7 and Bi-therapy in HCV Patients Resistant After 12 Weeks of Bi-therapy (ECLIPSE 1)
Official title: A PHASE I/IIa DOSE ESCALATION STUDY IN ASIA OF REPEATED ADMINISTRATION OF "CYT107" (Glyco-r-hIL-7) ADDED ON TREATMENT IN GENOTYPE 1 HCV INFECTED PATIENTS RESISTANT TO PEGYLATED INTERFERON-ALPHA AND RIBAVIRIN
Study type: INTERVENTIONAL
Overall status: COMPLETED
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
viral disease
liver disease
Lead sponsor: Cytheris SA
Sponsor class: INDUSTRY
First posted: 2009-12-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety of a new experimental drug, IL-7, in people with HCV infection resistant after 12 weeks of bi-therapy.

Detailed description: This is a Phase I inter-patient dose-escalation study assessing weekly doses of Interleukin-7 (CYT107) in adult patients infected by Genotype 1 Virus of Hepatitis C and resistant to standard treatment with Peg-Interferon and Ribavirin (biotherapy)after 12 weeks of this standard bi-therapy.

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 a subcutaneous administration of CYT107 per week for a total of 4 administrations.

Groups of 3 to 6 patients will be entered at each dose level of CYT107. Four dose levels are planned.

Eligible patients will a cycle of four weekly injections at a defined dose level in addition to the bi-therapy. Standard bi-therapy will continue 4 weeks after CYT107 treatment discontinuation. The duration of study is approximately 11 weeks including screening period.

Participants have 1 hospitalization overnight and 8 clinic visits. The four administrations are sub-cutaneous and are given as a shot under the skin in the arm or abdomen or leg.

During the study visits the following may be done:

* Medical history, physical examination, blood tests every visit.
* Electrocardiogram (EKG)
* Chest x-ray study
* Liver/spleen imaging
* Blood sample collections at frequent intervals
* Urine tests several times during the study.

Eligibility criteria: Main Inclusion Criteria:

* Genotype I infected patients
* Age \> 18 years
* Absence of early viral response to a first treatment with PEG-interferon-alpha plus ribavirin given for at least 12 weeks. Absence of early viral response (EVR) will be defined as detectable HCV with a decrease HCV RNA load \< 2 logs, measured by a quantitative PCR tests, as compared to baseline levels measured by a similar technique
* Ongoing treatment by PEG-interferon-alpha plus ribavirin at study entry

Main Exclusion Criteria:

* Infection by HBV
* Infection by HIV-1 and /or HIV-2
* Apart from HCV infection, presence of active infection requiring a specific treatment or a hospitalization
* Cirrhosis (Metavir F4) assessed by biopsy or FibroScan® or by liver biopsy within the last 6 months prior CYT107 treatment initiation. If assessed by Fibroscan® patients with a result \> 10 KPa will be excluded
* Other liver disease (notably from alcoholic, metabolic or immunological origin)
* Body mass index (BMI) \> 30kg/m2
* Inability to give informed consent
* Administration of growth factors (G-CSF, EPO) within the 12 weeks of the combination therapy

Primary outcomes:
measure: Safety of biologically active doses of CYT107 added to a standard bi-therapy in patients with a chronic infection by a genotype 1 Hepatitis C Virus (HCV) not responding to this combination therapy 12 weeks after its initiation.
timeFrame: 8 weeks after start of CYT107
Secondary outcomes:
measure: Pharmacokinetics and pharmacodynamics of CYT107 in this patients population.
timeFrame: As primary
measure: potential anti-viral effect of CYT107
timeFrame: As primary
measure: immune specific response to HCV
timeFrame: As primary
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: San Raffaele Scientific Institute
city: Zurich
country: Switzerland
facility: University of Zurich
Study officials:
affiliation: University of Zurich / Saint Gallen
name: Tilman Gerlach
role: STUDY_CHAIR
References: