Hepatitis, Hepatitis C
Conditions
Keywords
Hepatitis C, Cepeginterferon alfa, Peginterferon, Treatment
Brief summary
The purpose of the study is to demonstrate the noninferiority of Algeron 1.5 and 2.0 μg/kg/week in combination with ribavirin compared to PegIntron in combination with ribavirin in the treatment of chronic hepatitis C, and to determine therapeutic dose of Algeron.
Detailed description
After 12 weeks of treatment, an assessment of treatment efficacy was performed, i.e. rates of rapid (after 4 weeks) and early (after 12 weeks) virologic responses according to serum HCV RNA level PCR data. In patients without virologic response after 12 weeks, AVT was discontinued, and they were withdrawn from the study. Patients with EVR were enrolled in a follow-up period. During the follow-up period, patients of the first and the second group will receive Algeron in the selected therapeutic dose in combination with ribavirin, patients of the third group - PegIntron in combination with ribavirin during 12 or 36 weeks (depending on a genotype of the virus), afterwards they will be followed up without therapy for 24 weeks.
Interventions
Sponsors
Biocad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent to participate in the study. 2. Hepatitis С virus infection (genotypes 1а, 1b, 2, 3, 4) confirmed by a positive quantitative PCR (HCV RNA \> 50 IU/ml). 3. Males and females aged from 18 to 70 years inclusive. 4. Body mass index of 18 - 30 kg/m inclusive. 5. Increased ALT level (\> 40, \< 400 IU/L), documented at least twice within the last 6 months. 6. Preserved protein synthetic liver function (i.e. INR \< 1.7, albumin \> 35 g/l). 7. No signs of hepatic encephalopathy or abdominal fluid retention according to clinical and ultrasound examination. 8. Fertile patients and their partners agree to use barrier contraception throughout the study and 7 months after its completion.
Exclusion criteria
1. Intolerance of IFN alpha formulations, ribavirin or any components of these drugs according to the past medical history. 2. Infection by hepatitis B virus or HIV. 3. Past history of HCV treatment with IFN alfa or pegylated IFN alfa formulations. 4. Administration of interferons and/or interferon inducing drugs for any indication within 1 month prior to the enrollment into the study. 5. Cholestatic hepatitis (conjugated bilirubin, alkaline phosphatase, ALT levels of more than 5 ULN). 6. Decompensated liver cirrhosis confirmed by laboratory findings (Child-Pugh class B, С) or ultrasound examination. 7. Any documented autoimmune diseases. 8. Hematologic (hemoglobin \< 130 g/L for males and \< 120 g/L for females; neutrophils \< 1.5 х109/L; platelets \< 90 х109/L) or biochemical abnormalities (creatinine level of more than 1.5 ULN, creatinine clearance less than 50 mL/min). 9. Documented diagnosis of hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia). 10. Heavy depression, any other mental disorders, which in the Investigator's opinion can be contraindications for antiviral treatment. 11. Epilepsy and/or other functional disorders of the central nervous system. 12. Abnormal thyroid function (TTH level beyond the normal values). 13. Malignant neoplasms. 14. Pregnancy, lactation period. 15. Severe comorbidities (for example, severe hypertension, severe coronary heart disease, decompensated diabetes mellitus), which in the Investigator's opinion can be contraindications for antiviral treatment. 16. Documented rare hereditary diseases, such as intolerance of lactose, sucrose, fructose, lactase deficiency or glucose-galactose malabsorption. 17. Current alcohol or drug abuse, which in the Investigator's opinion can be contraindications for antiviral treatment or restrict treatment compliance. 18. Simultaneous participation in other clinical trials or prior participation in this or another clinical trial within less than 30 days after its completion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Randomized Patients Achieving Early Virologic Response (EVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) or ≥ 2log10 Decrease of Viral Load After 12 Weeks of Study Treatment. | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Number of Randomized Patients Achieving Rapid Virologic Response (RVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) After 4 Weeks of Treatment. | 4 weeks |
| Number of Randomized Patients Achieving Sustained Virologic Response (SVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) 24 Weeks After Last Dose of Study Treatment. | 24 weeks after last dose of study treatment |
| Number of Patients Who Have Undetectable HCV RNA (< 15 IU/ml) at the End of Treatment. | After 24 weeks of treatment for patients with genotype 2 or 3 and after 48 weeks of treatment for patients with genotype 1 or 4. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity | Weeks 0, 12, 24, 48 (for patients with genotype 1 or 4) and 24 weeks after last dose of study treatment | Number of randomized patients with neutralizing antibodies to IFN alfa on weeks 0, 12, 24, 48 (for patients with genotype 1 or 4) and 24 weeks after last dose of study treatment. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Algeron 1.5 μg/kg Algeron 1.5 μg/kg of body weight weekly subcutaneously in combination with ribavirin daily orally in a daily dose of 800 mg (patients with body weight \< 65 kg), 1000 mg (patients with body weight of 65-85 kg inclusive), 1200 mg (patients with body weight of 86-105 kg inclusive) or 1400 mg (patients with body weight \> 105 kg).
Algeron: 1.5 μg/kg or 2.0 μg/kg of body weight weekly subcutaneously | 50 |
| Algeron 2.0 μg/kg Algeron 2.0 μg/kg of body weight weekly subcutaneously in combination with ribavirin daily orally in a daily dose of 800 mg (patients with body weight \< 65 kg), 1000 mg (patients with body weight of 65-85 kg inclusive), 1200 mg (patients with body weight of 86-105 kg inclusive) or 1400 mg (patients with body weight \> 105 kg).
Algeron: 1.5 μg/kg or 2.0 μg/kg of body weight weekly subcutaneously | 50 |
| PegIntron PegIntron 1.5 μg/kg of body weight weekly subcutaneously in combination with ribavirin daily orally in a daily dose of 800 mg (patients with body weight \< 65 kg), 1000 mg (patients with body weight of 65-85 kg inclusive), 1200 mg (patients with body weight of 86-105 kg inclusive) or 1400 mg (patients with body weight \> 105 kg).
PegIntron: 1.5 μg/kg/week subcutaneously in combination with ribavirin | 50 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| After 12 Weeks | Adverse Event | 2 | 0 | 5 |
| After 12 Weeks | Lack of Efficacy | 3 | 1 | 4 |
| After 12 Weeks | Protocol Violation | 1 | 1 | 1 |
| After 12 Weeks | Withdrawal by Subject | 1 | 1 | 1 |
| First 12 Weeks of Treatment | Adverse Event | 0 | 1 | 2 |
| First 12 Weeks of Treatment | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | PegIntron | Algeron 2.0 μg/kg | Algeron 1.5 μg/kg |
|---|---|---|---|---|
| Age, Continuous | 35 years | 36 years | 34 years | 35 years |
| HCV genotype HCV 1a | 7 participants | 2 participants | 1 participants | 4 participants |
| HCV genotype HCV 1b | 74 participants | 26 participants | 26 participants | 22 participants |
| HCV genotype HCV 2 | 5 participants | 1 participants | 2 participants | 2 participants |
| HCV genotype HCV 3 | 64 participants | 21 participants | 21 participants | 22 participants |
| Initial Viral load High (>8х10^5 IU/ml) | 47 participants | 14 participants | 16 participants | 17 participants |
| Initial Viral load Low (≤8х10^5 IU/ml) | 103 participants | 36 participants | 34 participants | 33 participants |
| Interleukin 28B (IL-28B) genotype C/C | 49 participants | 13 participants | 17 participants | 19 participants |
| Interleukin 28B (IL-28B) genotype C/T | 76 participants | 26 participants | 26 participants | 24 participants |
| Interleukin 28B (IL-28B) genotype T/T | 25 participants | 11 participants | 7 participants | 7 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 149 Participants | 50 Participants | 49 Participants | 50 Participants |
| Region of Enrollment Russian Federation | 150 participants | 50 participants | 50 participants | 50 participants |
| Sex: Female, Male Female | 44 Participants | 15 Participants | 16 Participants | 13 Participants |
| Sex: Female, Male Male | 106 Participants | 35 Participants | 34 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 101 / 101 | 50 / 50 |
| serious Total, serious adverse events | 2 / 101 | 2 / 50 |
Outcome results
Primary
Number of Randomized Patients Achieving Early Virologic Response (EVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) or ≥ 2log10 Decrease of Viral Load After 12 Weeks of Study Treatment.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Algeron 1.5 μg/kg | Number of Randomized Patients Achieving Early Virologic Response (EVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) or ≥ 2log10 Decrease of Viral Load After 12 Weeks of Study Treatment. | 47 participants |
| Algeron 2.0 μg/kg | Number of Randomized Patients Achieving Early Virologic Response (EVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) or ≥ 2log10 Decrease of Viral Load After 12 Weeks of Study Treatment. | 47 participants |
| PegIntron | Number of Randomized Patients Achieving Early Virologic Response (EVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) or ≥ 2log10 Decrease of Viral Load After 12 Weeks of Study Treatment. | 44 participants |
Secondary
Number of Patients Who Have Undetectable HCV RNA (< 15 IU/ml) at the End of Treatment.
Time frame: After 24 weeks of treatment for patients with genotype 2 or 3 and after 48 weeks of treatment for patients with genotype 1 or 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Algeron 1.5 μg/kg | Number of Patients Who Have Undetectable HCV RNA (< 15 IU/ml) at the End of Treatment. | 88 participants |
| Algeron 2.0 μg/kg | Number of Patients Who Have Undetectable HCV RNA (< 15 IU/ml) at the End of Treatment. | 38 participants |
Secondary
Number of Randomized Patients Achieving Rapid Virologic Response (RVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) After 4 Weeks of Treatment.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Algeron 1.5 μg/kg | Number of Randomized Patients Achieving Rapid Virologic Response (RVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) After 4 Weeks of Treatment. | 32 participants |
| Algeron 2.0 μg/kg | Number of Randomized Patients Achieving Rapid Virologic Response (RVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) After 4 Weeks of Treatment. | 28 participants |
| PegIntron | Number of Randomized Patients Achieving Rapid Virologic Response (RVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) After 4 Weeks of Treatment. | 33 participants |
Secondary
Number of Randomized Patients Achieving Sustained Virologic Response (SVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) 24 Weeks After Last Dose of Study Treatment.
Time frame: 24 weeks after last dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Algeron 1.5 μg/kg | Number of Randomized Patients Achieving Sustained Virologic Response (SVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) 24 Weeks After Last Dose of Study Treatment. | 75 participants |
| Algeron 2.0 μg/kg | Number of Randomized Patients Achieving Sustained Virologic Response (SVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) 24 Weeks After Last Dose of Study Treatment. | 34 participants |
Other Pre-specified
Immunogenicity
Number of randomized patients with neutralizing antibodies to IFN alfa on weeks 0, 12, 24, 48 (for patients with genotype 1 or 4) and 24 weeks after last dose of study treatment.
Time frame: Weeks 0, 12, 24, 48 (for patients with genotype 1 or 4) and 24 weeks after last dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Algeron 1.5 μg/kg | Immunogenicity | 0 participants |
| Algeron 2.0 μg/kg | Immunogenicity | 0 participants |