Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

February 15, 2007
March 10, 2016
July 2006
April 2012   (final data collection date for primary outcome measure)
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).
Sustained virological response (serum HBV DNA <20,000 copies/mL) after each treatment, and after 24 weeks of follow-up.
Complete list of historical versions of study NCT00442572 on ClinicalTrials.gov Archive Site
  • 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).
Efficacy: Durability of response (serum HBV DNA <20,000 copies/mL, & normalization of ALT) every 12 weeks, & after follow-up; loss of HBsAg and seroconversion, & HBV DNA BLQ, at end of follow-up; changes in liver fibrosis. Safety: AEs, lab. parameters.
Not Provided
Not Provided
 
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).
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)
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hepatitis B, Chronic
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.
  • 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.
    Intervention: Drug: PEGASYS [peginterferon alfa-2a]
  • No Intervention: No Intervention
    Participants were on non- specific anti-viral treatment.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
April 2012
April 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Bulgaria
 
NCT00442572
ML20020
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP