Back to resultsSOFIA-LTT Study: A Study of Intermittent Long Term Treatment With PEGASYS (Peginterferon Alfa-2a (40KD)) in Patients With HBeAg Negative Chronic Hepatitis B (CHB).
Primary Purpose
Hepatitis B, Chronic
Status
Completed
Phase
Phase 2
Locations
Bulgaria
Study Type
Interventional
Intervention
PEGASYS [peginterferon alfa-2a]
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B, Chronic
Eligibility 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.
Sites / Locations
- Mhat St. Ivan Rilski; Clinic of Gastroenterology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
PEGASYS
No Intervention
Arm Description
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.
Participants were on non- specific anti-viral treatment.
Outcomes
Primary Outcome Measures
Percentage of Participants With Stable Virological Response
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
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
Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.
Percentage of Participants With HBsAg Seroconversion
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
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
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
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
The hemoglobin values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
Mean Change From Baseline in Hematology
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
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
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
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
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
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
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)
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
The Triiodothyronine (T3) and thyroxine (T4) values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00442572
Brief Title
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).
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
July 3, 2006 (Actual)
Primary Completion Date
April 23, 2012 (Actual)
Study Completion Date
April 23, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PEGASYS
Arm Type
Experimental
Arm Description
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.
Arm Title
No Intervention
Arm Type
No Intervention
Arm Description
Participants were on non- specific anti-viral treatment.
Intervention Type
Drug
Intervention Name(s)
PEGASYS [peginterferon alfa-2a]
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Stable Virological Response
Description
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).
Time Frame
Up to Week 108
Secondary Outcome Measure Information:
Title
Percentage of Participants With Stable Virological and Biochemical Response
Description
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).
Time Frame
Up to Week 108
Title
Percentage of Participants With Loss of Hepatitis B Surface Antigen
Description
Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.
Time Frame
Up to Week 108
Title
Percentage of Participants With HBsAg Seroconversion
Description
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).
Time Frame
Up to Week 108
Title
Percentage of Participants With HBV DNA Levels Under the Lower Limit (Serum HBV DNA Level < 300 Copies/ml) For a Significant Quantity
Description
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.
Time Frame
Up to Week 108
Title
Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index Scores For Change in Liver Fibrosis
Description
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.
Time Frame
Up to Week 108
Title
Mean Change From Baseline in HBsAg Levels
Description
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.
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Hemoglobin
Description
The hemoglobin values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Hematology
Description
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).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Clinical Chemistry
Description
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).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Protein and Indirect Albumin
Description
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).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Bilirubin Indirect and Bilirubin Direct
Description
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).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Blood Urea
Description
The blood urea was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Creatinine and Uric Acid
Description
The creatinine and uric acid values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Blood Glucose
Description
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).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Thyroid Stimulating Hormone (TSH)
Description
The TSH was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
Time Frame
Up to Week 108
Title
Mean Change From Baseline in Triiodothyronine and Thyroxine
Description
The Triiodothyronine (T3) and thyroxine (T4) values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
Time Frame
Up to Week 108
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Mhat St. Ivan Rilski; Clinic of Gastroenterology
City
Sofia
ZIP/Postal Code
1612
Country
Bulgaria
12. IPD Sharing Statement
Learn more about this trial
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).
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