Algeron (Cepeginterferon Alfa-2b) Compared With PegIntron (Peginterferon Alfa-2b) for Treatment of Chronic Hepatitis C

Multicenter Open-label Randomized Prospective Clinical Study of Efficacy and Safety of Algeron (Cepeginterferon Alfa-2b) in Comparison With PegIntron (Peginterferon Alfa-2b) in the Combined Treatment of Chronic Hepatitis C

The purpose of the study is to demonstrate the noninferiority of Algeron 1.5 and 2.0 μg/kg/week in combination with ribavirin compared to PegIntron in combination with ribavirin in the treatment of chronic hepatitis C, and to determine therapeutic dose of Algeron.

Study Overview

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

Detailed Description

After 12 weeks of treatment, an assessment of treatment efficacy was performed, i.e. rates of rapid (after 4 weeks) and early (after 12 weeks) virologic responses according to serum HCV RNA level PCR data. In patients without virologic response after 12 weeks, AVT was discontinued, and they were withdrawn from the study. Patients with EVR were enrolled in a follow-up period. During the follow-up period, patients of the first and the second group will receive Algeron in the selected therapeutic dose in combination with ribavirin, patients of the third group - PegIntron in combination with ribavirin during 12 or 36 weeks (depending on a genotype of the virus), afterwards they will be followed up without therapy for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 127473
    • Moscow State University of Medicine and Dentistry

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. Hepatitis С virus infection (genotypes 1а, 1b, 2, 3, 4) confirmed by a positive quantitative PCR (HCV RNA > 50 IU/ml).
3. Males and females aged from 18 to 70 years inclusive.
4. Body mass index of 18 - 30 kg/m inclusive.
5. Increased ALT level (> 40, < 400 IU/L), documented at least twice within the last 6 months.
6. Preserved protein synthetic liver function (i.e. INR < 1.7, albumin > 35 g/l).
7. No signs of hepatic encephalopathy or abdominal fluid retention according to clinical and ultrasound examination.
8. Fertile patients and their partners agree to use barrier contraception throughout the study and 7 months after its completion.

Exclusion Criteria:

1. Intolerance of IFN alpha formulations, ribavirin or any components of these drugs according to the past medical history.
2. Infection by hepatitis B virus or HIV.
3. Past history of HCV treatment with IFN alfa or pegylated IFN alfa formulations.
4. Administration of interferons and/or interferon inducing drugs for any indication within 1 month prior to the enrollment into the study.
5. Cholestatic hepatitis (conjugated bilirubin, alkaline phosphatase, ALT levels of more than 5 ULN).
6. Decompensated liver cirrhosis confirmed by laboratory findings (Child-Pugh class B, С) or ultrasound examination.
7. Any documented autoimmune diseases.
8. Hematologic (hemoglobin < 130 g/L for males and < 120 g/L for females; neutrophils < 1.5 х109/L; platelets < 90 х109/L) or biochemical abnormalities (creatinine level of more than 1.5 ULN, creatinine clearance less than 50 mL/min).
9. Documented diagnosis of hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia).
10. Heavy depression, any other mental disorders, which in the Investigator's opinion can be contraindications for antiviral treatment.
11. Epilepsy and/or other functional disorders of the central nervous system.
12. Abnormal thyroid function (TTH level beyond the normal values).
13. Malignant neoplasms.
14. Pregnancy, lactation period.
15. Severe comorbidities (for example, severe hypertension, severe coronary heart disease, decompensated diabetes mellitus), which in the Investigator's opinion can be contraindications for antiviral treatment.
16. Documented rare hereditary diseases, such as intolerance of lactose, sucrose, fructose, lactase deficiency or glucose-galactose malabsorption.
17. Current alcohol or drug abuse, which in the Investigator's opinion can be contraindications for antiviral treatment or restrict treatment compliance.
18. Simultaneous participation in other clinical trials or prior participation in this or another clinical trial within less than 30 days after its completion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Algeron 1.5 μg/kg; Algeron 1.5 μg/kg of body weight weekly subcutaneously in combination with ribavirin daily orally in a daily dose of 800 mg (patients with body weight < 65 kg), 1000 mg (patients with body weight of 65-85 kg inclusive), 1200 mg (patients with body weight of 86-105 kg inclusive) or 1400 mg (patients with body weight > 105 kg).	Drug: Algeron; 1.5 μg/kg or 2.0 μg/kg of body weight weekly subcutaneously; Other Names: cepeginterferon alfa-2b; Drug: Ribavirin; 800-1400 mg/day orally
EXPERIMENTAL: Algeron 2.0 μg/kg; Algeron 2.0 μg/kg of body weight weekly subcutaneously in combination with ribavirin daily orally in a daily dose of 800 mg (patients with body weight < 65 kg), 1000 mg (patients with body weight of 65-85 kg inclusive), 1200 mg (patients with body weight of 86-105 kg inclusive) or 1400 mg (patients with body weight > 105 kg).	Drug: Algeron; 1.5 μg/kg or 2.0 μg/kg of body weight weekly subcutaneously; Other Names: cepeginterferon alfa-2b; Drug: Ribavirin; 800-1400 mg/day orally
ACTIVE_COMPARATOR: PegIntron; PegIntron 1.5 μg/kg of body weight weekly subcutaneously in combination with ribavirin daily orally in a daily dose of 800 mg (patients with body weight < 65 kg), 1000 mg (patients with body weight of 65-85 kg inclusive), 1200 mg (patients with body weight of 86-105 kg inclusive) or 1400 mg (patients with body weight > 105 kg).	Drug: Ribavirin; 800-1400 mg/day orally; Drug: PegIntron; 1.5 μg/kg/week subcutaneously in combination with ribavirin; Other Names: Peginterferon alfa-2b

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number 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	Time Frame
Number of Randomized Patients Achieving Rapid Virologic Response (RVR) - Negative PCR Result for HCV RNA (< 15 IU/ml) After 4 Weeks of Treatment.	4 weeks
Number 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
Number of Patients Who Have 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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Number of randomized patients with neutralizing antibodies to IFN alfa on weeks 0, 12, 24, 48 (for patients with genotype 1 or 4) and 24 weeks after last dose of study treatment.	Weeks 0, 12, 24, 48 (for patients with genotype 1 or 4) and 24 weeks after last dose of study treatment

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Principal Investigator: Olga Znoyko, professor, Moscow State University of Medicine and Dentistry; Principal Investigator: Marina Maevskaya, professor, The First Moscow State Sechenov Medical University; Principal Investigator: Svetlana Kizhlo, Health Department "Center for Prevention and Control of AIDS and Infectious Diseases"; Principal Investigator: Natalia Petrochenkova, Smolensk State Medical Academy; Principal Investigator: Semen Maximov, Moscow State University of Medicine and Dentistry; Principal Investigator: Firaja Nagimova, Kazan State Medical University; Principal Investigator: Vladimur Yakovlev, 7. St. Petersburg State Institution of Health "Clinical Infectious Diseases Hospital named SP Botkin"

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: November 30, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (ESTIMATE): December 4, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 18, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2b
• Other Study ID Numbers: PEG-IFNа-2