Chronic Hepatitis C Virus Infection, Genotype 1, Relapses, Treatment-Experienced Patients
Conditions
Keywords
Chronic Hepatitis C Viral Infection, Interferon alfa-5, Interferon
Brief summary
The general aim of this study is to determine if 3 MIU of IFN-α5 in monotherapy, and 1,5 MIU of IFN-α5 combined with 1,5 MIU of IFN- α2b, are safe dose levels as well as to investigate the antiviral efficacy and pharmacodynamics (PD) of such doses and drugs in treatment-experienced HCV patients with genotype 1 chronic infection, after 29 days of treatment. It is also intended to determine pharmacokinetics (PK) of the safe dose achieved of IFN-α5 in monotherapy.
Interventions
DRUGInterferon α-5
3 MIU or safe dose used three times a week (TIW) in alternate days in monotherapy. 29 days of treatment. Subcutaneous injection.
DRUGInterferon-α5 plus Interferon-α 2b
Interferon-α5 plus Interferon-α 2b. 1.5 MIU each, or safe dose used TIW in alternate days in combined therapy. 29 days of treatment. Subcutaneous injection.
DRUGInterferon α-2b (INTRON® A)
3 million IU TIW in alternate days in monotherapy. 29 days of treatment. Subcutaneous injection.
Sponsors
Digna Biotech S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥18 years old, 2. With chronic hepatitis C (CHC) infection diagnosed by seropositivity for anti-HCV antibodies or detectable HCV-RNA, at least 6 months prior to screening. 3. Patients with CHC infection of genotype 1 (1a, 1b or mixed 1a/1b) 4. Defined as relapsers: those CHC patients who had achieved virologic response (HCV-RNA non detectable) at any time during the standard care of treatment for CHC with IFN-α2 or PegIFN-α2 + ribavirin, and maintained it trough the end of treatment at week 48 weeks, but HCV-RNA detection occurs before 6 months post-treatment. 5. In whom liver cirrhosis has been ruled out through fibro-scan or liver biopsy within 24 months prior to study enrolment. 6. With a serum HCV viral load ≥ 100.000 IU/mL at screening 7. With alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) serum measurements at screening less than 5 times of their upper limits of normal (ULN) 8. With a body mass index (BMI) of at least 18 kg/m2, but not exceeding 36 kg/m2. 9. For female subjects with childbearing potential: use of a known highly effective method of birth control 10. For male subjects with partners of child bearing potential: use of appropriate contraceptive methods. 11. Is able to effectively communicate with the investigator and other testing center personnel. 12. Is able to participate and willing to give written informed consent and comply with the study restrictions.
Exclusion criteria
(principal): 1. Hepatitis C infection of genotype 2, 3 or 4 or any mixed genotype (1/2, 1/3 and 1/4). 2. A positive ELISA for HIV-1 or HIV-2. 3. Hepatitis B virus (HBV) infection based on the presence of HBsAg. 4. Hepatitis A virus (HAV) infection based on the presence of antiHAV-IgM. (AM 4)Criteria deleted 5. Decompensated liver disease, or history of decompensated liver disease. 6. History or other evidence of a medical condition associated with decompensated renal, immunologically mediated, chronic pulmonary, cardiac, thyroid, severe retinopathy, severe psychiatric, organ transplantation, cancer, seizure disorder or pancreatitis diseases. 7. An active or suspected malignancy or history of malignancy within the last five years. 8. Patients with a documented drug and alcohol addiction free history of at least 12 months who are, in the opinion of the investigator unlikely to relapse, may be enrolled in the study. 9. Positive results for drug abuse at screening.Occasional use of cannabis previously to randomization is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safe dose level | 29 days of treatment | PRIMARY ENDPOINTS OF PHASE I * To determine if 3 MIU of IFN-α5 are well tolerated and if not, to find a safe dose level for IFN-α5. * To determine if 1.5 MIU of IFN-α5 in combination with 1.5 MIU of IFN-α2b (IFN-α5 + IFN-α2b) are well tolerated and if not, to find a safe dose level for the combination of IFN-α5 and IFN-α2b. PRIMARY ENDPOINTS OF PHASE II * To analyze IFN-α5 preliminary antiviral efficacy at the dose of 3 MIU, or the safe dose level identified in Phase I. * Primary safety endpoints: Occurrence of AE (classified into mild, moderate and severe) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pharmacodynamic and pharmacokinetic parameters | 29 days of treatment | SECONDARY ENDPOINTS OF PHASE I * To obtain pharmacokinetic parameters of IFN-α5 in monotherapy after single and multiple dose administration * To obtain pharmacodynamic parameters of IFN-α5 in monotherapy and in combination with IFN-α2b SECONDARY ENDPOINTS OF PHASE II * To analyze IFN-α5 + IFN-α2b preliminary antiviral efficacy and comparison between IFN-α5 in monotherapy, IFN-α5 + IFN-α2b and IFN-α2b in monotherapy. * To obtain pharmacodynamic parameters after treatment with IFN-α5, IFN-α5 + IFN-α2b or IFN-α2b. |
Countries
Spain
Outcome results
None listed