Clinical trial NCT01889433: An Open-label Comparative Efficacy and Safety Study of Algeron (Cepeginterferon Alfa-2b) in Treatment-naive Patients With Chronic Hepatitis C
Official title: An Open-label Randomized Multicenter Phase III Clinical Study Comparing Safety and Efficacy of Algeron (Cepeginterferon Alfa-2b) and Ribavirin With Pegasys (Peginterferon Alfa-2a) and Ribavirin for Treatment of Patients With Chronic Hepatitis C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis
Hepatitis C
Keywords: Hepatitis C
Cepeginterferon alfa
Peginterferon
Treatment
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2013-06-28
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to demonstrate the noninferiority of Algeron in combination with ribavirin compared to Pegasys in combination with ribavirin in the treatment of chronic hepatitis C.

Detailed description: The course of treatment in both groups shall be 12 weeks, and efficacy analysis, i.e. rate of rapid (after the 4th week) and early (after the 12th week) virologic response will be based on PCR data. For patients with treatment failure after the 12th week the antiviral therapy shall be discontinued. All patients who require further anti-viral treatment will receive a combination treatment with Algeron / Pegasys and ribavirin for another 12 or 36 weeks (depending on the HCV genotype). Sustained virologic response will be assessed 24 weeks after last dose of study treatment.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent to participate in the study.
2. Chronic HCV infection (genotypes 1а, 1b, 2, 3, 4) with detectable HCV RNA \>6 month before the screening visit or abnormal ALT levels for \>6 month before the screening visit.
3. Male and female patients, 18 to 70 years of age, inclusive.
4. Body mass index of 18 - 30 kg/m2.
5. Preserved protein synthetic liver function (INR \< 1.7, albumin \> 35 g/l).
6. No signs of hepatic encephalopathy or abdominal fluid retention according to clinical and ultrasound examination.
7. Fertile patients and their partners agree to use barrier contraception throughout the study treatment and 7 months after it.
8. Patient must have documentation of fibroscan within 1 year before the screening visit or agree to have a fibroscan within the screening period.

Exclusion Criteria:

1. Intolerance to IFN alfa, ribavirin or any components of this preparations confirmed by past medical history.
2. Infection by hepatitis B, A, E virus or HIV (co-infection).
3. Any other documented significant liver disease (drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis, biliary cirrohosis, etc.).
4. Past history of HCV treatment with IFN alfa or pegylated IFN alfa.
5. Administration of injectable and non-injectable interferons and/or some interferon inducers for any indication (other than HCV) for one month before enrollment into the study.
6. Cholestatic hepatitis (level of conjugated bilirubin, alkaline phosphatase, G-GTP exceeding the upper normal level by more than 5 times).
7. Decompensated liver cirrhosis confirmed by laboratory findings (class B, С according to Child-Pugh) or ultrasound examination.
8. Any documented autoimmune diseases (e.g., Crohn's disease, ulcerative colitis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, scleroderma, autoimmune haemolytic anemia, severe psoriasis).
9. Hemoglobin not lower than low normal level; neutrophils \< 1.5 х109/L; platelets \< 90 х109/L; creatinin level exceeding the upper normal level by more than 1.5 times, ALT level exceeding the upper normal level by more than 10 times.
10. Documented hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia).
11. Severe depression, schizophrenia, other mental disorders, which from the investigator's point of view are a contraindication for anti-viral treatment.
12. Epilepsy and/or disorder of function of the central nervous system.
13. Abnormal thyroid function (TTH level beyond the normal values).
14. Diagnosed or suspected hepatocellular carcinoma as evidenced by screening alfa-fetoprotein (AFP) of ≥ upper normal level.
15. Antinuclear antibody (ANA) titer ≥1:640 at screening and/or evidence of autoimmune hepatitis on liver biopsy.
16. Malignant neoplasms.
17. Pregnancy, lactation period.
18. Severe comorbidities (for example, severe hypertension, severe coronary heart disease, decompensated diabetes mellitus) that represent a contraindication for anti-viral treatment.
19. Documented rare hereditary diseases, such as intolerance of lactose, sucrose, fructose, lactase deficiency or glucose-galactose malabsorption.
20. Known drug or alcohol abuse or signs of drug/alcohol abuse in present, which from the investigator's point of view are a contraindication for anti-viral treatment or restrict adherence to the treatment regimen.
21. Simultaneous participation in other clinical studies less than 30 days before enrollment into this study or previous participation in this clinical study.

Primary outcomes:
measure: EVR
timeFrame: 12 weeks
Secondary outcomes:
measure: RVR
timeFrame: 4 weeks
measure: SVR (24)
timeFrame: 24 weeks after last dose of study treatment
measure: EOT
timeFrame: 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
measure: Biochemical Response
timeFrame: 12, 24, 48 weeks of treatment, and 24 weeks after last dose of study treatment
measure: Histological Response
timeFrame: 12 weeks of treatment and 24 weeks after last dose of study treatment
Other outcomes:
measure: Immunogenicity
timeFrame: Week 0, 12, 24, and additionally for patients with HCV 1, 4 genotype - week 48 after first administration of Algeron / Pegasys and 24 weeks after last dose of study treatment
Locations:
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Indore
country: India
facility: Suyash Hospital Pvt. Ltd. Opposite M.G.M Medical College A.B. Road
city: Lucknow
country: India
facility: M V Hospital & Research Center
city: Mumbai
country: India
facility: Bhatia Hospital, Medical Research Society Tardeo Road, Grant Road (W)
city: Pune
country: India
facility: Medipoint Hospitals Pvt. Ltd.
city: Moscow
country: Russian Federation
facility: State Budgetary Higher Vocational Education Institution A.I. Evdokimov Moscow State University of Medicine and Dentistry
city: Moscow
country: Russian Federation
facility: State Budgetary Higher Vocational Education Institution I.M. Sechenov First Moscow State Medical University
city: Moscow
country: Russian Federation
facility: State Public Healthcare Institution of the City of Moscow "Infectious Disease Clinical Hospital No. 1"
city: Samara
country: Russian Federation
facility: LLC Medical Company "Hepatolog"
city: Saratov
country: Russian Federation
facility: Municipal Healthcare Institution City Clinical Hospital No.2 named after V.I. Razumovsky
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital
city: Smolensk
country: Russian Federation
facility: State Budgetary Higher Vocational Education Institution Smolensk State Medical Academy
city: St. Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution Research Institute of Influenza
city: St. Petersburg
country: Russian Federation
facility: Federal State Military Higher Vocational Education Institution S.M. Kirov Military Medical Academy
city: Stavropol
country: Russian Federation
facility: State Budgetary Higher Vocational Education Institution Stavropol State Medical Academy
city: Tyumen
country: Russian Federation
facility: State Medical and Preventive Institution of the Tyumen Region "Advisory and Diagnostic Center"
city: Bangkok
country: Thailand
facility: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital
Study officials:
affiliation: Federal State Military Higher Vocational Education Institution S.M. Kirov Military Medical Academy
name: Konstantin Zhdanov, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Higher Vocational Education Institution A.I. Evdokimov Moscow State University of Medicine and Dentistry
name: Olga Znoyko, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Higher Vocational Education Institution I.M. Sechenov First Moscow State Medical University
name: Marina Maevskaya, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: LLC Medical Company "Hepatolog", Samara, Russia
name: Vjacheslav Morozov
role: PRINCIPAL_INVESTIGATOR
affiliation: Municipal Healthcare Institution City Clinical Hospital No.2 named after V.I. Razumovsky, Healthcare Committee at the Administration of "Saratov City" Municipal District
name: Natalja Mironova, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Public Healthcare Institution of the City of Moscow "Infectious Disease Clinical Hospital No. 1", Moscow City Health Department
name: Elena Nurmuhametova, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Higher Vocational Education Institution Stavropol State Medical Academy, Ministry of Health of the Russian Federation
name: Victor Pasechnikov, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Higher Vocational Education Institution Smolensk State Medical Academy
name: Natalia Petrochenkova, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Budgetary Institution Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg
name: Tamara Sologub, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional State Healthcare Institution "Smolensk Regional Clinical Hospital"
name: Vladimir Rafalskiy, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: State Medical and Preventive Institution of the Tyumen Region "Advisory and Diagnostic Center", Tyumen
name: Evgeniy Chesnokov, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: M V Hospital & Research Center, 314/30 Mirza Mandi, Chowk 226003, Lucknow 226003, Uttar Pradesh, India
name: Sandeep Gupta, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Bhatia Hospital, Medical Research Society Tardeo Road, Grant Road (W), Maharashtra, India
name: Tariq A Patil, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Medipoint Hospitals Pvt. Ltd. Maharashtra, India
name: Mandar Doiphode, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Suyash Hospital Pvt. Ltd. Opposite M.G.M Medical College A.B. Road, Madhya Pradesh, India
name: G S Malpani, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Bangkoknoi, Bangkok, Thailand
name: Tawesak Tanwandee
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Sriphum, Muang, Chiang Mai, Thailand
name: Thongsawat Satawat
role: PRINCIPAL_INVESTIGATOR
References: