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SOFIA-LTT Study: A Study of Intermittent Long Term Treatment With PEGASYS (Peginterferon Alfa-2a (40KD)) in Patients With HBeAg Negative Chronic Hepatitis B (CHB).

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00442572
First received: February 15, 2007
Last updated: March 10, 2016
Last verified: March 2016
  Purpose
This 2 arm study will evaluate the efficacy and safety of intermittent treatment with PEGASYS in HBeAg negative patients with chronic hepatitis B who have demonstrated virological and biochemical response after treatment with interferon alfa. After 48 weeks therapy with interferon alfa, and 24 weeks treatment-free follow-up, eligible patients will be randomized into the PEGASYS or the observational group. Those in the PEGASYS group will receive 4 therapeutic cycles of long term intermittent treatment with PEGASYS (135 micrograms sc weekly for 12 weeks, followed by a treatment-free period of 12 weeks) and those in the observational arm will receive no specific antiviral treatment. The anticipated time on study treatment is 1-2 years, and the target sample size is 100 individuals.

Condition Intervention Phase
Hepatitis B, Chronic
Drug: PEGASYS [peginterferon alfa-2a]
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Stop Progression of Fibrosis by Administration of Intermittent Continuous Treatment With Peginterferon Alfa-2a. Open-label, Randomized Efficacy and Safety Clinical Trial of Intermittent Continuous Treatment With Peginterferon Alfa-2a (PEGASYS) in Patients With HBeAg Negative Hepatitis B Responding to Prior Treatment With Interferon Alfa (SOFIA -LTT)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Stable Virological Response [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    Stable virological response is serum Hepatitis B virus deoxyribonucleic acid (HBV DNA) <20 000 copies/ml during the treatment (after each 12 weeks) and after the follow-up period (24 weeks after the last treatment period).


Secondary Outcome Measures:
  • Percentage of Participants With Stable Virological and Biochemical Response [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    All participants who achieved virological response (serum HBV DNA < 20 000 copies/ml) and biochemical response (stable normalization of their alanine transaminase [ALT]) during the treatment cycle (after each 12 weeks) and after the follow-up period (24 weeks after the last treatment period).

  • Percentage of Participants With Loss of Hepatitis B Surface Antigen [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.

  • Percentage of Participants With HBsAg Seroconversion [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The development of antibodies against HBsAg is known as HBsAg seroconversion. It signifies clearance of HBsAg and resolution of the chronic infection. НBsAg seroconversion is the final goal of anti-hepatitis B virus treatment and it is closest to the definition of "cure" but in practice it is very rare in HBeAg-negative chronic hepatitis B (CHB).

  • Percentage of Participants With HBV DNA Levels Under the Lower Limit (Serum HBV DNA Level < 300 Copies/ml) For a Significant Quantity [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    HBV DNA level, or viral load, is an indicator of viral replication. Higher HBV DNA levels are usually associated with an increased risk of liver disease and hepatocellular carcinoma. HBV DNA level typically falls in response to effective antiviral treatment.

  • Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index Scores For Change in Liver Fibrosis [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    Fibrosis-4 (FIB-4) and Aspartate Aminotransferase to Platelet Ratio Index (APRI) are non-invasive scoring systems, which are calculated on the basis of laboratory tests that indicates the level of liver fibrosis. The APRI scores are calculated based on Aspartate Aminotransferase (AST) levels and platelet counts whereas FIB-4 scores are calculated based on platelets, ALT, AST and age. For APRI, the scores are interpreted as ≤ 0.5 is 81% sensitive and 50% specific for a diagnosis of significant fibrosis in chronic hepatitis C (CHC), where as a cut-off > 1.5 is 35% sensitive and 91% specific for the diagnosis of significant fibrosis. The majority of biomarker panels will produce inconclusive results for a proportion of participants falling within the indeterminate range (between 0.5 and 1.5) for a specific fibrosis end-point. For FIB-4, the scores are interpreted as FIB-4 score of < 1.45: absence of cirrhosis, FIB-4 score of 1.45 to 3.25: inconclusive, FIB-4 score > 3.25: cirrhosis.

  • Mean Change From Baseline in HBsAg Levels [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    An early decrease in HBsAg from baseline to Weeks 12 or 24 has been identified as further on-treatment predictor for sustained HBsAg clearance and virological response in HBeAg negative participants.

  • Mean Change From Baseline in Hemoglobin [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The hemoglobin values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Hematology [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The hematology parameters included erythrocytes, leucocytes, basophils, eosinophils, lymphocytes, monocytes, thrombocytes. All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Clinical Chemistry [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The clinical chemistry parameters included alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP). All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Protein and Indirect Albumin [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The clinical chemistry parameters included indirect protein and albumin. All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and no intervention).

  • Mean Change From Baseline in Bilirubin Indirect and Bilirubin Direct [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The laboratory parameters included bilirubin indirect and bilirubin direct. All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Blood Urea [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The blood urea was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Creatinine and Uric Acid [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The creatinine and uric acid values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Blood Glucose [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The blood glucose was measured for change from baseline. All blood glucose values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Thyroid Stimulating Hormone (TSH) [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The TSH was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

  • Mean Change From Baseline in Triiodothyronine and Thyroxine [ Time Frame: Up to Week 108 ] [ Designated as safety issue: No ]
    The Triiodothyronine (T3) and thyroxine (T4) values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).


Enrollment: 21
Study Start Date: July 2006
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PEGASYS
Participants received 4 treatment cycles of continuous intermittent treatment with PEGASYS® (Peginterferon alfa-2a) . Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 micrograms in 0.5 ml solution in prefilled syringes, applied once weekly subcutaneously and followed by 12 weeks period without treatment.
Drug: PEGASYS [peginterferon alfa-2a]
There were 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 micrograms in 0.5 ml solution in prefilled syringes, applied once weekly subcutaneously and followed by 12 weeks period without treatment.
No Intervention: No Intervention
Participants were on non- specific anti-viral treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • liver disease consistent with CHB;
  • evidence of chronic HBeAg-negative CHB prior to initial course of interferon alfa;
  • patients who have responded to previous 48 weeks treatment with interferon alfa.

Exclusion Criteria:

  • coinfection with HCV, HDV or HIV;
  • decompensated liver disease, hepatocellular cancer, or evidence of a medical condition associated with chronic liver disease other than viral hepatitis;
  • any other systemic antiviral, antineoplastic or immunomodulatory treatment <=6 months prior to first dose of randomized treatment.
  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: NCT00442572

Locations
Bulgaria
Sofia, Bulgaria, 1612
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00442572     History of Changes
Other Study ID Numbers: ML20020 
Study First Received: February 15, 2007
Results First Received: December 8, 2015
Last Updated: March 10, 2016
Health Authority: Bulgaria: Bulgarian Drug Agency

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016