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

Biocad

Status and phase: Completed; Phase 3

Conditions: Hepatitis C/ Human Immunodeficiency Virus Coinfection; Hepatitis C; Hepatitis

Treatments: Drug: Algeron; Drug: PegIntron

Study type: Interventional

Funder types: Industry

Identifiers

NCT02103439

BCD-016-4

Details and patient eligibility

About

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

Full 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.

Enrollment: 140 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

Algeron

Experimental group

Description:

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)

Treatment:

Drug: Algeron

PegIntron

Active Comparator group

Description:

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).

Treatment:

Drug: PegIntron