- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00442572
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).
March 9, 2017 updated by: Hoffmann-La Roche
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
21
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Sofia, Bulgaria, 1612
- Mhat St. Ivan Rilski; Clinic of Gastroenterology
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / 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.
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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.
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No Intervention: No Intervention
Participants were on non- specific anti-viral treatment.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Stable Virological Response
Time Frame: Up to Week 108
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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).
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Up to Week 108
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Stable Virological and Biochemical Response
Time Frame: Up to Week 108
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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).
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Up to Week 108
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Percentage of Participants With Loss of Hepatitis B Surface Antigen
Time Frame: Up to Week 108
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Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.
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Up to Week 108
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Percentage of Participants With HBsAg Seroconversion
Time Frame: Up to Week 108
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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).
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Up to Week 108
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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
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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.
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Up to Week 108
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Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index Scores For Change in Liver Fibrosis
Time Frame: Up to Week 108
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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.
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Up to Week 108
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Mean Change From Baseline in HBsAg Levels
Time Frame: Up to Week 108
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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.
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Up to Week 108
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Mean Change From Baseline in Hemoglobin
Time Frame: Up to Week 108
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The hemoglobin values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
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Up to Week 108
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Mean Change From Baseline in Hematology
Time Frame: Up to Week 108
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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).
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Up to Week 108
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Mean Change From Baseline in Clinical Chemistry
Time Frame: Up to Week 108
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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).
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Up to Week 108
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Mean Change From Baseline in Protein and Indirect Albumin
Time Frame: Up to Week 108
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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).
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Up to Week 108
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Mean Change From Baseline in Bilirubin Indirect and Bilirubin Direct
Time Frame: Up to Week 108
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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).
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Up to Week 108
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Mean Change From Baseline in Blood Urea
Time Frame: Up to Week 108
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The blood urea was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
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Up to Week 108
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Mean Change From Baseline in Creatinine and Uric Acid
Time Frame: Up to Week 108
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The creatinine and uric acid values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
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Up to Week 108
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Mean Change From Baseline in Blood Glucose
Time Frame: Up to Week 108
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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).
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Up to Week 108
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Mean Change From Baseline in Thyroid Stimulating Hormone (TSH)
Time Frame: Up to Week 108
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The TSH was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
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Up to Week 108
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Mean Change From Baseline in Triiodothyronine and Thyroxine
Time Frame: Up to Week 108
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The Triiodothyronine (T3) and thyroxine (T4) values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).
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Up to Week 108
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 3, 2006
Primary Completion (Actual)
April 23, 2012
Study Completion (Actual)
April 23, 2012
Study Registration Dates
First Submitted
February 15, 2007
First Submitted That Met QC Criteria
March 1, 2007
First Posted (Estimate)
March 2, 2007
Study Record Updates
Last Update Posted (Actual)
April 6, 2017
Last Update Submitted That Met QC Criteria
March 9, 2017
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Anti-Infective Agents
- Antiviral Agents
- Peginterferon alfa-2a
Other Study ID Numbers
- ML20020
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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