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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Biocad
Sponsor:
Information provided by (Responsible Party):
Biocad
ClinicalTrials.gov Identifier:
NCT01889433
First received: June 26, 2013
Last updated: July 28, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis
Hepatitis C
Drug: Algeron
Drug: Pegasys
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biocad:

Primary Outcome Measures:
  • EVR [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • RVR [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Proportion of randomized patients achieving rapid virologic response (RVR) - negative PCR result for HCV RNA (< 15 IU/ml) after 4 weeks of treatment.

  • SVR (24) [ Time Frame: 24 weeks after last dose of study treatment ] [ Designated as safety issue: Yes ]
    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

  • EOT [ 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 ] [ Designated as safety issue: Yes ]
    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).

  • Biochemical Response [ Time Frame: 12, 24, 48 weeks of treatment, and 24 weeks after last dose of study treatment ] [ Designated as safety issue: Yes ]
    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.

  • Histological Response [ Time Frame: 12 weeks of treatment and 24 weeks after last dose of study treatment ] [ Designated as safety issue: Yes ]
    Proportion of patients who have histological response, defined by a 1 level decrease in total METAVIR score measured on Fibroscan


Other Outcome Measures:
  • Immunogenicity [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Proportion of randomized patients with neutralizing antibodies to IFN alfa


Estimated Enrollment: 500
Study Start Date: November 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Peginterferon alfa-2a

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01889433

Contacts
Contact: Andrey Biryulin, MD (495) 992 66 28 ext 925
Contact: Yulia Linkova, PhD (495) 992 66 28 ext 930 linkova@biocad.ru

Locations
Belarus
Gomel Regional Clinical Hospital Recruiting
Gomel, Belarus, 246029
Vitebsk Regional Clinical Hospital Recruiting
Vitebsk, Belarus, 210037
India
Suyash Hospital Pvt. Ltd. Opposite M.G.M Medical College A.B. Road Not yet recruiting
Indore, India, 452001
M V Hospital & Research Center Not yet recruiting
Lucknow, India, 226003
Bhatia Hospital, Medical Research Society Tardeo Road, Grant Road (W) Not yet recruiting
Mumbai, India, 400007
Medipoint Hospitals Pvt. Ltd. Not yet recruiting
Pune, India, 411007
Russian Federation
State Budgetary Higher Vocational Education Institution A.I. Evdokimov Moscow State University of Medicine and Dentistry Enrolling by invitation
Moscow, Russian Federation, 127473
State Public Healthcare Institution of the City of Moscow "Infectious Disease Clinical Hospital No. 1" Recruiting
Moscow, Russian Federation
State Budgetary Higher Vocational Education Institution I.M. Sechenov First Moscow State Medical University Recruiting
Moscow, Russian Federation
LLC Medical Company "Hepatolog" Recruiting
Samara, Russian Federation
Municipal Healthcare Institution City Clinical Hospital No.2 named after V.I. Razumovsky Recruiting
Saratov, Russian Federation
Smolensk Regional Clinical Hospital Recruiting
Smolensk, Russian Federation
State Budgetary Higher Vocational Education Institution Smolensk State Medical Academy Recruiting
Smolensk, Russian Federation
Federal State Military Higher Vocational Education Institution S.M. Kirov Military Medical Academy Recruiting
St. Petersburg, Russian Federation
Federal State Budgetary Institution Research Institute of Influenza Recruiting
St. Petersburg, Russian Federation
State Budgetary Higher Vocational Education Institution Stavropol State Medical Academy Recruiting
Stavropol, Russian Federation
State Medical and Preventive Institution of the Tyumen Region "Advisory and Diagnostic Center" Recruiting
Tyumen, Russian Federation
Thailand
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital Recruiting
Bangkok, Thailand, 10700
Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital Recruiting
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Biocad
ClinicalTrials.gov Identifier: NCT01889433     History of Changes
Other Study ID Numbers: BCD-016-3
Study First Received: June 26, 2013
Last Updated: July 28, 2014
Health Authority: Russia: Ministry of Health of the Russian Federation

Keywords provided by Biocad:
Hepatitis C
Cepeginterferon alfa
Peginterferon
Treatment

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014