Clinical trial NCT02103439: 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 Human Immunodeficiency Virus-1 Infected Patients
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 Human Immunodeficiency Virus-1 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis
Hepatitis C
Hepatitis C/ Human Immunodeficiency Virus Coinfection
Keywords: Hepatitis C
Cepeginterferon alfa
Peginterferon
Treatment
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2014-04-03
Enrollment: 140
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 PegIntron in combination with ribavirin in treatment of chronic hepatitis C in Human Immunodeficiency Virus-1 infected patients

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 polymerase chain reaction 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 criteria: Inclusion Criteria:

* Signed Informed Consent Form.
* Chronic hepatitis C (genotypes 1а, 1b, 2, 3, 4) confirmed by positive result of hepatitis C virus ribonucleic acid during \> 6 months before screening visit or accompanied with increase in alanine aminotransferase (ALT) level \> 6 months before screening visit.
* Confirmed Human Immunodeficiency Virus-1 infection based on enzyme-linked immunosorbent assay and immune blotting results.
* Clinically sustained phase of Human Immunodeficiency Virus-1 infection with absence of active opportunistic Human Immunodeficiency Virus-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, Human Immunodeficiency Virus ribonucleic acid ≤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 (International Normalized Ratio \< 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 Hepatitis C Virus treatment with interferon alfa or pegylated interferon 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, gamma glutamyltransferase, exceeding upper normal limit 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 erythematosus, idiopathic thrombocytopenic purpura, scleroderma, autoimmune hemolytic anemia, severe psoriasis).
* Deviations of hematologic (hemoglobin less than lower normal limit; neutrophils \< 1.5 x 10\^9/l; thrombocytes \< 90 x 10\^9/ l) and biochemical (creatinine level \> 1.5 times higher upper normal limit, ALT is \> 10 times higher upper normal limit) 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 thyroid stimulating hormone out of the normal range).
* Documentary confirmed or suspected hepatocellular carcinoma based on the results of alfa-fetoprotein (AFP) assay ≥ upper normal limit.
* 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 Human Immunodeficiency Virus-1 with immunotherapeutic vaccines within 90 days prior to screening.
* Necessity in assignment of antimycobacterial 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.

Primary outcomes:
measure: Early Virological Response
timeFrame: 12 weeks
measure: Early Virological Response in Patients With Different Hepatitis C Virus Genotypes
timeFrame: 12 weeks
Secondary outcomes:
measure: Rapid Virological Response
timeFrame: 4 weeks
measure: Rapid Virological Response in Patients With Different Hepatitis C Virus Genotypes
timeFrame: 4 weeks
measure: Viral Breakthrough
timeFrame: screening data and at 4 or 12 weeks of treatment.
measure: Biochemical Response
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Kazan
country: Russian Federation
facility: 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
state: Republic Of Tatarstan
city: Nizhny Novgorod
country: Russian Federation
facility: State Institution of Nizhny Novgorod region "Regional Center for Prevention and Control of AIDS and other infectious diseases"
city: Sankt-Petersburg
country: Russian Federation
facility: State Healthcare Institution Center for the Prevention and Control of AIDS and infectious diseases of the city, St.Petersburg CityHealth Department
city: Saratov
country: Russian Federation
facility: State Budgetary Higher Vocational Education Institution V.I. Razumovsky Saratov State University of medicine
city: Vladivostok
country: Russian Federation
facility: State Budgetary Higher Vocational Education Institution Pacific State Medical University, Ministry of Health of the Russian Federation
city: Volgograd
country: Russian Federation
facility: State Healthcare Institution "Volgograd Regional Center for the Prevention and Control of AIDS and infectious diseases"
Study officials:
affiliation: State Institution of Nizhny Novgorod region "Regional Center for Prevention and Control of AIDS and other infectious diseases"
name: Gregory Moshkovich, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: 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
name: Firaya Nagimova, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Healthcare Institution "Volgograd Regional Center for the Prevention and Control of AIDS and infectious diseases"
name: Oleg Kozyrev, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Higher Vocational Education Institution V.I. Razumovsky Saratov State University of medicine
name: Andrey Shuldyakov, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Healthcare Institution Center for the Prevention and Control of AIDS and infectious diseases of the city, St.Petersburg CityHealth Department
name: Vadim Rassokhin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budgetary Higher Vocational Education Institution Pacific State Medical University, Ministry of Health of the Russian Federation
name: Lidia Sklar, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References: