An Open-label Comparative Efficacy and Safety Study of Algeron (Cepeginterferon Alfa-2b) in Treatment-naive Patients With Chronic Hepatitis C

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis; Hepatitis C
• Intervention / Treatment: Drug: Algeron; Drug: Pegasys

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.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Gomel, Belarus, 246029
    • Gomel Regional Clinical Hospital
  • Vitebsk, Belarus, 210037
    • Vitebsk Regional Clinical Hospital
• India
  • Indore, India, 452001
    • Suyash Hospital Pvt. Ltd. Opposite M.G.M Medical College A.B. Road
  • Lucknow, India, 226003
    • M V Hospital & Research Center
  • Mumbai, India, 400007
    • Bhatia Hospital, Medical Research Society Tardeo Road, Grant Road (W)
  • Pune, India, 411007
    • Medipoint Hospitals Pvt. Ltd.
• Russian Federation
  • Moscow, Russian Federation
    • State Budgetary Higher Vocational Education Institution I.M. Sechenov First Moscow State Medical University
  • Moscow, Russian Federation, 127473
    • State Budgetary Higher Vocational Education Institution A.I. Evdokimov Moscow State University of Medicine and Dentistry
  • Moscow, Russian Federation
    • State Public Healthcare Institution of the City of Moscow "Infectious Disease Clinical Hospital No. 1"
  • Samara, Russian Federation
    • LLC Medical Company "Hepatolog"
  • Saratov, Russian Federation
    • Municipal Healthcare Institution City Clinical Hospital No.2 named after V.I. Razumovsky
  • Smolensk, Russian Federation
    • Smolensk Regional Clinical Hospital
  • Smolensk, Russian Federation
    • State Budgetary Higher Vocational Education Institution Smolensk State Medical Academy
  • St. Petersburg, Russian Federation
    • Federal State Budgetary Institution Research Institute of Influenza
  • St. Petersburg, Russian Federation
    • Federal State Military Higher Vocational Education Institution S.M. Kirov Military Medical Academy
  • Stavropol, Russian Federation
    • State Budgetary Higher Vocational Education Institution Stavropol State Medical Academy
  • Tyumen, Russian Federation
    • State Medical and Preventive Institution of the Tyumen Region "Advisory and Diagnostic Center"
• Thailand
  • Bangkok, Thailand, 10700
    • Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital
  • Chiang Mai, Thailand, 50200
    • Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Algeron; Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg).	Drug: Algeron; 1.5 µg/kg of body weight subcutaneously, once a week; Other Names: Cepeginterferon alfa-2b
ACTIVE_COMPARATOR: Pegasys; Pegasys in a dose of 180 µg subcutaneously, once a week, in combination with Rebetol, orally, at a daily dose of 800 mg for patients with genotype 2 or 3, and for genotypes 1 or 4 at a daily dose of 1000 mg (for body weight <75 kg) or 1200 mg (for body weight ≥75 kg)	Drug: Pegasys; 180 µg subcutaneously, once a week; Other Names: Peginterferon alfa-2a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EVR	Proportion 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
RVR	Proportion of randomized patients achieving rapid virologic response (RVR) - negative PCR result for HCV RNA (< 15 IU/ml) after 4 weeks of treatment.	4 weeks
SVR (24)	Proportion 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
EOT	Proportion of randomized patients achieving end-of-treatment response (EOT) -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).	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
Biochemical Response	Proportion of patients who have ALT level ≤ than upper normal level after 12 weeks of treatment, 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) and 24 weeks after last dose of study treatment.	12, 24, 48 weeks of treatment, and 24 weeks after last dose of study treatment
Histological Response	Proportion of patients who have histological response, defined by a 1 level decrease in total METAVIR score measured on Fibroscan	12 weeks of treatment and 24 weeks after last dose of study treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Proportion of randomized patients with neutralizing antibodies to IFN alfa	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

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Principal Investigator: Konstantin Zhdanov, Professor, Federal State Military Higher Vocational Education Institution S.M. Kirov Military Medical Academy; Principal Investigator: Olga Znoyko, Professor, State Budgetary Higher Vocational Education Institution A.I. Evdokimov Moscow State University of Medicine and Dentistry; Principal Investigator: Marina Maevskaya, Professor, State Budgetary Higher Vocational Education Institution I.M. Sechenov First Moscow State Medical University; Principal Investigator: Vjacheslav Morozov, LLC Medical Company "Hepatolog", Samara, Russia; Principal Investigator: Natalja Mironova, PhD, Municipal Healthcare Institution City Clinical Hospital No.2 named after V.I. Razumovsky, Healthcare Committee at the Administration of "Saratov City" Municipal District; Principal Investigator: Elena Nurmuhametova, PhD, State Public Healthcare Institution of the City of Moscow "Infectious Disease Clinical Hospital No. 1", Moscow City Health Department; Principal Investigator: Victor Pasechnikov, Professor, State Budgetary Higher Vocational Education Institution Stavropol State Medical Academy, Ministry of Health of the Russian Federation; Principal Investigator: Natalia Petrochenkova, PhD, State Budgetary Higher Vocational Education Institution Smolensk State Medical Academy; Principal Investigator: Tamara Sologub, Professor, Federal State Budgetary Institution Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg; Principal Investigator: Vladimir Rafalskiy, Professor, Regional State Healthcare Institution "Smolensk Regional Clinical Hospital"; Principal Investigator: Evgeniy Chesnokov, Professor, State Medical and Preventive Institution of the Tyumen Region "Advisory and Diagnostic Center", Tyumen; Principal Investigator: Sandeep Gupta, Dr, M V Hospital & Research Center, 314/30 Mirza Mandi, Chowk 226003, Lucknow 226003, Uttar Pradesh, India; Principal Investigator: Tariq A Patil, Dr, Bhatia Hospital, Medical Research Society Tardeo Road, Grant Road (W), Maharashtra, India; Principal Investigator: Mandar Doiphode, Dr, Medipoint Hospitals Pvt. Ltd. Maharashtra, India; Principal Investigator: G S Malpani, Dr, Suyash Hospital Pvt. Ltd. Opposite M.G.M Medical College A.B. Road, Madhya Pradesh, India; Principal Investigator: Tawesak Tanwandee, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Bangkoknoi, Bangkok, Thailand; Principal Investigator: Thongsawat Satawat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Sriphum, Muang, Chiang Mai, Thailand

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 10, 2013
• Primary Completion (ACTUAL): December 2, 2015
• Study Completion (ACTUAL): December 2, 2015

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (ESTIMATE): June 28, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 16, 2018
• Last Update Submitted That Met QC Criteria: July 13, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Treatment; Hepatitis C; Peginterferon; Cepeginterferon alfa
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2a
• Other Study ID Numbers: BCD-016-3