An Open-label Randomized Multicenter Phase III Clinical Study Comparing Safety and Efficacy of Algeron (Cepeginterferon Alfa-2b) and and PegIntron (Peginterferon Alfa-2b) in Combination With Ribavirin as Combined Treatment of Chronic Hepatitis C in HIV-1 Infected Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biocad
ClinicalTrials.gov Identifier:
NCT02103439
First received: April 1, 2014
Last updated: NA
Last verified: April 2014
History: No changes posted
  Purpose

The purpose of the study is to demonstrate the noninferiority of Algeron in combination with ribavirin compared to PegIntron in combination with ribavirin in treatment of chronic hepatitis C in HIV-1 infected patients


Condition Intervention Phase
Hepatitis
Hepatitis C
Coinfection HCV and HIV
Drug: Algeron
Drug: PegIntron
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Open-label Randomized, Comparative Clinical Study to Evaluate Efficacy and Safety of Algeron (Cepeginterferon Alfa-2b, CJSC "BIOCAD", Russia) With Ribavirin Compared to PegIntron (Peginterferon Alfa-2b, Schering-Plough Labo N.V., Belgium) With Ribavirin in Treatment of Chronic Hepatitis C in HIV-1 Infected Patients

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: 48 weeks of treatment ] [ Designated as safety issue: Yes ]
    Proportion of randomized patients achieving end-of-treatment response (EOT) -undetectable HCV RNA (< 15 IU/ml) after 48 weeks of treatment

  • Biochemical Response [ Time Frame: 12, 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 48 weeks of treatment) and 24 weeks after last dose of study treatment

  • Histological Response [ Time Frame: screening data and in 24 weeks after treatment completion ] [ Designated as safety issue: Yes ]
    Proportion of patients with decreased in fibrosis level by 1 level on the METAVIR score compared to screening data and in 24 weeks after treatment completion.

  • Viral breakthrough [ Time Frame: screening data and at 4 or 12 or 24 weeks of treatment. ] [ Designated as safety issue: Yes ]
    Proportion of patients in each groups with level of HCV RNA > 15 IU/ml after HCV RNA was not present or HCV RNA was increased by more than 1log10 from baseline at 4 or 12 or 24 weeks of treatment


Enrollment: 140
Study Start Date: September 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2014 (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: PegIntron
PegIntron 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: PegIntron
1.5 µg/kg of body weight subcutaneously, once a week
Other Name: peginterferon alfa-2b

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 / PegIntron and ribavirin for another 36 weeks. 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:

  • Signed Informed Consent Form.
  • Chronic hepatitis C (genotypes 1а, 1b, 2, 3, 4) confirmed by positive result of HCV RNA during > 6 months before screening visit or accompanied with increase in ALT level > 6 months before screening visit.
  • Confirmed HIV-1 infection based on ELISA and immune blotting results.
  • Clinically sustained phase of HIV-1 infection with absence of active opportunistic HIV-associated diseases for at least 30 calendar days before inclusion in the study.
  • Level of CD4+-lymphocytes is not less than 500 cells/mm3 for patients not requiring highly active antiretroviral therapy and which will not be assigned to antiretroviral therapy during the study period.
  • For patients receiving sustained highly active antiretroviral therapy for not less than 12 weeks and planning to continue comply with this treatment regimen during the following 24 weeks, level of CD4+-lymphocytes ≥300 cells/mm3, HIV RNA ≤50 copies/ml.
  • Men and women aged 18 to 70 inclusively.
  • Body mass index in the range of 18 - 30 kg/m2 inclusively .
  • Preserved protein-synthetizing liver function (INR < 1.7, albumin > 35 g/l).
  • Absence of signs of hepatic encephalopathy and ascites according to clinical examination and ultrasound examination.
  • Patients with preserved child-bearing potential and their partners agree to use barrier method of contraception during the whole period of therapy and during 7 months after the treatment completion.
  • Documentary confirmed results of liver elastography (fibroscan) during last year before enrollment in the study or patient agreement to undergo this examination during screening.

Exclusion Criteria:

  • Intolerance of alfa-interferons, ribavirin or any components of tested drug product based on medical history.
  • Presence of hepatitis B, A, E markers.
  • Presence of documentary confirmed clinically significant concurrent liver diseases (alcoholic liver cirrhosis, drug-induced liver cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis, biliary cirrhosis etc.).
  • Past history of HCV treatment with IFN alfa or pegylated IFN alfa.
  • For patients receiving sustained highly active antiretroviral therapy - presence of nevirapine, stavudine, zidovudine, didanosine in treatment regimen.
  • Use of injectable and non-injectable interferons alfa/ interferon inducers for any indication (except for hepatitis C), radiotherapy, cytotoxic chemotherapy for one month prior to inclusion in the study.
  • Cholestic hepatitis (level of direct bilirubin, alkaline phosphatase, GGT, exceeding UNL in > 5 times).
  • Decompensated liver cirrhosis confirmed with results of laboratory analyses (Child-Pugh class B, C) or ultrasound examination.
  • Any documentary confirmed autoimmune diseases (such as Crohn's disease, ulcerative colitis, systemic lupus erythemathosus, idiopathic thrombocytopenic purpura, scleroderma, autoimmune hemolytic anemia, severe psoriasis).
  • Deviations of hematologic (hemoglobin less than lower normal limit; neutrophils < 1.5 x 109/l; thrombocytes < 90 x 109/ l) and biochemical (creatinine level > 1.5 times higher UNL , ALT is > 10 times higher UNL ) parameters.
  • Documentary confirmed diagnosis of hemoglobinopathy (for example, thalassemia, sickle-cell anemia).
  • Severe depression, schizophrenia, any other mental disorders which according to the investigator are contraindications for antiviral treatment.
  • Epilepsy and/or central nervous system disorder.
  • Disorder of thyroid function (level of TSH out of the normal range).
  • Documentary confirmed or suspected hepatocellular carcinoma based on the results of alfa-fetoprotein (AFP) assay ≥ UNL.
  • Antinuclear antibodies (ANA) titer measured at screening is not less than 1:640 or documentary confirmed signs of autoimmune hepatitis based on the results of biopsy.
  • Documentary confirmed malignant neoplasms.
  • Documentary confirmed lung diseases associated with respiratory failure.
  • Treatment of HIV-1 with immunotherapeutic vaccines within 90 days prior to screening.
  • Necessity in assignment of antimicobacterial therapy.
  • Pregnancy, lactation period.
  • Documentary confirmed retinopathy (for example, cytomegalovirus retinitis, macular degeneration).
  • Severe concurrent diseases (for example, severe arterial hypertension, sever coronary heart disease, heart failure, decompensated diabetes mellitus and other) which are contraindications for antiviral therapy according to the investigator opinion.
  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: NCT02103439

Locations
Russian Federation
State Public Healthcare Institution National Center for the Prevention and Control of AIDS and other infectious diseases of the Ministry of Health of the Republic of Tatarstan
Kazan, Republic of Tatarstan, Russian Federation, 420097
State Institution of Nizhny Novgorod region "Regional Center for Prevention and Control of AIDS and other infectious diseases"
Nizhny Novgorod, Russian Federation, 603005
State Healthcare Institution Center for the Prevention and Control of AIDS and infectious diseases of the city, St.Petersburg CityHealth Department
Sankt-Petersburg, Russian Federation, 190103
State Budgetary Higher Vocational Education Institution V.I. Razumovsky Saratov State University of medicine
Saratov, Russian Federation, 410012
State Budgetary Higher Vocational Education Institution Pacific State Medical University, Ministry of Health of the Russian Federation
Vladivostok, Russian Federation, 690002
State Healthcare Institution "Volgograd Regional Center for the Prevention and Control of AIDS and infectious diseases"
Volgograd, Russian Federation, 400040
Sponsors and Collaborators
Biocad
Investigators
Principal Investigator: Gregory Moshkovich, M.D. State Institution of Nizhny Novgorod region "Regional Center for Prevention and Control of AIDS and other infectious diseases"
Principal Investigator: Firaya Nagimova, PhD State Public Healthcare Institution National Center for the Prevention and Control of AIDS and other infectious diseases of the Ministry of Health of the Republic of Tatarstan
Principal Investigator: Oleg Kozyrev, PhD State Healthcare Institution "Volgograd Regional Center for the Prevention and Control of AIDS and infectious diseases"
Principal Investigator: Andrey Shuldyakov, M.D., PhD State Budgetary Higher Vocational Education Institution V.I. Razumovsky Saratov State University of medicine
Principal Investigator: Vadim Rassokhin, PhD State Healthcare Institution Center for the Prevention and Control of AIDS and infectious diseases of the city, St.Petersburg CityHealth Department
Principal Investigator: Lidia Sklar, M.D., PhD State Budgetary Higher Vocational Education Institution Pacific State Medical University, Ministry of Health of the Russian Federation
  More Information

No publications provided

Responsible Party: Biocad
ClinicalTrials.gov Identifier: NCT02103439     History of Changes
Other Study ID Numbers: BCD-016-4
Study First Received: April 1, 2014
Last Updated: April 1, 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
Coinfection
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Infection
Parasitic Diseases
Ribavirin
Peginterferon alfa-2b
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014