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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01889433
• Other study ID #: BCD-016-3
• Status: Completed
• Phase: Phase 3
• Start date: July 10, 2013
• Est. completion date: December 2, 2015

Study information

• Verified date: July 2018
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: December 2, 2015
• Est. primary completion date: December 2, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent to participate in the study.

2. Chronic HCV infection (genotypes 1?, 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, ? 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 ?109/L; platelets < 90 ?109/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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Algeron
1.5 µg/kg of body weight subcutaneously, once a week
• Pegasys
180 µg subcutaneously, once a week

Locations

Country	Name	City	State
Belarus	Gomel Regional Clinical Hospital	Gomel
Belarus	Vitebsk Regional Clinical Hospital	Vitebsk
India	Suyash Hospital Pvt. Ltd. Opposite M.G.M Medical College A.B. Road	Indore
India	M V Hospital & Research Center	Lucknow
India	Bhatia Hospital, Medical Research Society Tardeo Road, Grant Road (W)	Mumbai
India	Medipoint Hospitals Pvt. Ltd.	Pune
Russian Federation	State Budgetary Higher Vocational Education Institution A.I. Evdokimov Moscow State University of Medicine and Dentistry	Moscow
Russian Federation	State Budgetary Higher Vocational Education Institution I.M. Sechenov First Moscow State Medical University	Moscow
Russian Federation	State Public Healthcare Institution of the City of Moscow "Infectious Disease Clinical Hospital No. 1"	Moscow
Russian Federation	LLC Medical Company "Hepatolog"	Samara
Russian Federation	Municipal Healthcare Institution City Clinical Hospital No.2 named after V.I. Razumovsky	Saratov
Russian Federation	Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	State Budgetary Higher Vocational Education Institution Smolensk State Medical Academy	Smolensk
Russian Federation	Federal State Budgetary Institution Research Institute of Influenza	St. Petersburg
Russian Federation	Federal State Military Higher Vocational Education Institution S.M. Kirov Military Medical Academy	St. Petersburg
Russian Federation	State Budgetary Higher Vocational Education Institution Stavropol State Medical Academy	Stavropol
Russian Federation	State Medical and Preventive Institution of the Tyumen Region "Advisory and Diagnostic Center"	Tyumen
Thailand	Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital	Bangkok
Thailand	Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital	Chiang Mai

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

Belarus,  India,  Russian Federation,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunogenicity	Proportion of randomized patients with neutralizing antibodies to IFN alfa	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
Primary	EVR	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	12 weeks
Secondary	RVR	Proportion of randomized patients achieving rapid virologic response (RVR) - negative PCR result for HCV RNA (< 15 IU/ml) after 4 weeks of treatment.	4 weeks
Secondary	SVR (24)	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	24 weeks after last dose of study treatment
Secondary	EOT	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).	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
Secondary	Biochemical Response	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.	12, 24, 48 weeks of treatment, and 24 weeks after last dose of study treatment
Secondary	Histological Response	Proportion of patients who have histological response, defined by a 1 level decrease in total METAVIR score measured on Fibroscan	12 weeks of treatment and 24 weeks after last dose of study treatment