Clinical trial NCT01024894: Dose Escalation Study of Interleukin-7 (IL-7) and Bitherapy in Asiatic HCV Patients Resistant to Bitherapy
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: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hepatitis C
Keywords: interleukin-7
immune-based therapies
hepatitis C
chronic hepatitis
resistance to Peg-interferon and ribavirin bitherapy
immune specific responses to HCV
taiwan
phase 1/2a
viral disease
liver disease
Lead sponsor: Cytheris SA
Sponsor class: INDUSTRY
First posted: 2009-12-03
Enrollment: 15
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 is designed to evaluate the safety of biological active dose of a new experimental drug, IL-7, in combination with standard bi-therapy in Asiatic 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 Asiatic adult patients infected by virus of genotype 1 of Hepatitis C and resistant to standard treatment with Peg-Interferon and Ribavirin (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 one subcutaneous administration of CYT107 per week for a total of 4.

Groups of 3 to 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: Main Inclusion Criteria:

* HCV Genotype 1 infected patients
* Absence of viral response to previous treatments with pegylated interferon-alpha plus ribavirin
* Metavir ≤ F3 assessed by biopsy in the last 12 months

Main Exclusion Criteria:

* Active 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
* Other liver disease
* Body mass index (BMI) \> 30kg/m2
* Relapse after previous response to pegylated IFN alpha and ribavirin therapy
* Previous bi-therapy with pegylated IFN alpha and ribavirin not well tolerated (in particular treatment discontinuation)
* 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
* Inability to give informed consent

Primary outcomes:
measure: safety of biologically active doses of CYT107 added to a combination therapy by pegylated interferon-alpha and ribavirin in Asian patients with a chronic infection by a genotype 1 HCV not responding to this combination therapy
timeFrame: 12 weeks after start of CYT107
Secondary outcomes:
measure: Pharmacokinetics and pharmacodynamics of CYT107 in this patients population.
timeFrame: At short and mid terms follow-ups
measure: potential anti-viral effect of CYT107
timeFrame: 4 weeks and 12 weeks after start of CYT107
measure: long-term safety and viral load variations
timeFrame: 24 and 48 weeks after the start of CYT107
measure: immune specific response to HCV
timeFrame: 8 and 12 weeks after start of CYT107
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Taipe
country: Taiwan
facility: Cathay General Hospital
city: Taipe
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Kaohsiung Medical University
name: Wang-Long Chuang, MD
role: STUDY_CHAIR
References: