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).

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00442572
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Actual Duration (Months): 69.7
• Patients Per Site Per Month: 0.3

Study Details

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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)
• Actual Study Start Date: Jul 3, 2006
• Actual Primary Completion Date: Apr 23, 2012
• Actual Study Completion Date: Apr 23, 2012

Arms and Interventions

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.	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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Stable Virological Response [Up to Week 108]

   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

1. Percentage of Participants With Stable Virological and Biochemical Response [Up to Week 108]

   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).

2. Percentage of Participants With Loss of Hepatitis B Surface Antigen [Up to Week 108]

   Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.

3. Percentage of Participants With HBsAg Seroconversion [Up to Week 108]

   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).

4. Percentage of Participants With HBV DNA Levels Under the Lower Limit (Serum HBV DNA Level < 300 Copies/ml) For a Significant Quantity [Up to Week 108]

   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.

5. Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index Scores For Change in Liver Fibrosis [Up to Week 108]

   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.

6. Mean Change From Baseline in HBsAg Levels [Up to Week 108]

   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.

7. Mean Change From Baseline in Hemoglobin [Up to Week 108]

   The hemoglobin values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

8. Mean Change From Baseline in Hematology [Up to Week 108]

   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).

9. Mean Change From Baseline in Clinical Chemistry [Up to Week 108]

   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).

10. Mean Change From Baseline in Protein and Indirect Albumin [Up to Week 108]

    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).

11. Mean Change From Baseline in Bilirubin Indirect and Bilirubin Direct [Up to Week 108]

    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).

12. Mean Change From Baseline in Blood Urea [Up to Week 108]

    The blood urea was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

13. Mean Change From Baseline in Creatinine and Uric Acid [Up to Week 108]

    The creatinine and uric acid values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

14. Mean Change From Baseline in Blood Glucose [Up to Week 108]

    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).

15. Mean Change From Baseline in Thyroid Stimulating Hormone (TSH) [Up to Week 108]

    The TSH was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

16. Mean Change From Baseline in Triiodothyronine and Thyroxine [Up to Week 108]

    The Triiodothyronine (T3) and thyroxine (T4) values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Mhat St. Ivan Rilski; Clinic of Gastroenterology	Sofia		Bulgaria	1612

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00442572
• Other Study ID Numbers: ML20020
• First Posted: Mar 2, 2007
• Last Update Posted: Apr 6, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Peginterferon alfa-2a

Study Results

Participant Flow

Recruitment Details	All participants in this study were enrolled at one centre in Bulgaria from 03 July 2006 to 23 April 2012. Of the 21 participants enrolled, 17 participants were randomized to PEGASYS arm and 4 participants were randomized to no intervention arm.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a (PEGASYS®). Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 micrograms (µg) in 0.5 ml solution in prefilled syringes, applied once weekly subcutaneously (SC) and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Period Title: Overall Study
STARTED	17	4
COMPLETED	9	1
NOT COMPLETED	8	3

Baseline Characteristics

Arm/Group Title	PEGASYS	No Intervention	Total
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.	Total of all reporting groups
Overall Participants	17	4	21
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	44	38.5	42
Sex: Female, Male (Count of Participants)
Female	7 41.2%	0 0%	7 33.3%
Male	10 58.8%	4 100%	14 66.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment..	Participants were on non- specific anti-viral treatment.
Measure Participants	17	3
Week 12	100 588.2%	100.0 2500%
Week 24	52.9 311.2%	66.7 1667.5%
Week 36	52.9 311.2%	100.0 2500%
Week 48	47.1 277.1%	66.7 1667.5%
Week 60	47.1 277.1%	33.3 832.5%
Week 72	41.2 242.4%	33.3 832.5%
Week 84	41.2 242.4%	33.3 832.5%
Week 96	29.4 172.9%	33.3 832.5%
Week 108	29.4 172.9%	33.3 832.5%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	17	3
Week 12	100.0 588.2%	100.0 2500%
Week 24	52.9 311.2%	66.7 1667.5%
Week 36	52.9 311.2%	100.0 2500%
Week 48	47.1 277.1%	66.7 1667.5%
Week 60	47.1 277.1%	33.3 832.5%
Week 72	41.2 242.4%	33.3 832.5%
Week 84	41.2 242.4%	33.3 832.5%
Week 96	29.4 172.9%	33.3 832.5%
Week 108	29.4 172.9%	33.3 832.5%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	17	3
Number (95% Confidence Interval) [Percentage of Participants]	5.9 34.7%	0 0%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation. Data of participants available at the time of the assessment were included in the analysis. Only participants with HBsAg clearance were analyzed.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	1	0
Number [Percentage of Participants]	0 0%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who passed during at least one treatment period and had at least one efficacy and safety evaluation. HBV DNA levels below lower limit for significant quantity were not studied for no intervention arm participants.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	17	0
Number (95% Confidence Interval) [Percentage of Participants]	29.4 172.9%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	13	0
FIB-4	1.06
APRI	0.25

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation. Data of participants available at the time of the assessment were included in the analysis.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	17	3
Week 12, n=17,3	-1156.00	-240.50
Week 24, n=17,3	-1293.72	-146.00
Week 36, n=14,3	-3049.64	-564.00
Week 48, n=13, 3	-1591.78	-528.50
Week 60, n=11,1	-3096.56	-379.00
Week 72, n=10, 1	-3485.90	-34.00
Week 84, n=9, 1	201.40	-54.72
Week 96, n=14,1	-3011.75	-49.51
Week 108, n=12,0	-3368.13	NA

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Mean (Standard Deviation) [Gram/deciliter]	-1.73 (10.44)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Erythrocytes	0.08 (0.26)
Leukocytes	-1.72 (2.00)
Basophils	-0.18 (0.38)
Lymphocytes	5.56 (6.31)
Monocytes	1.87 (3.10)
Thrombocytes	-31.20 (36.40)
Eosinophils	0.92 (1.24)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
ALAT	5.56 (25.44)
ASAT	9.00 (27.76)
GGT	1.00 (3.70)
ALP	50.92 (38.00)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Protein indirect	-31.62 (38.70)
Albumin	-1.35 (1.71)

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Indirect bilirubin	-0.95 (3.38)
Direct bilirubin	-0.16 (0.77)

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Mean (Standard Deviation) [millimoles/liter]	-0.34 (1.23)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Creatinine	-3.65 (13.23)
Uric acid	-21.51 (130.42)

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Mean (Standard Deviation) [millimoles/ liter]	-0.06 (0.40)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
Mean (Standard Deviation) [milli-international units/liter]	0.67 (1.50)

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Arm/Group Title	PEGASYS	No Intervention
Arm/Group Description	Participants received 4 treatment cycles of continuous intermittent treatment with Peginterferon alfa-2a. Each cycle consisted of 12 weeks injection treatment with Peginterferon alfa-2a 135 µg in 0.5 ml solution in prefilled syringes, applied once weekly SC and followed by 12 weeks period without treatment.	Participants were on non- specific anti-viral treatment.
Measure Participants	12	0
T3, Week 108	0.19 (5.44)
T4, Week 108	-0.85 (4.99)

Adverse Events

Time Frame	Up to Week 108
Adverse Event Reporting Description	AE is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly.
Arm/Group Title	PEGASYS		No Intervention
Arm/Group Description	Participants received 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.		Participants were on non- specific anti-viral treatment.
All Cause Mortality
	PEGASYS		No Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PEGASYS		No Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	PEGASYS		No Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/17 (64.7%)		1/4 (25%)
Endocrine disorders
Hypothyroidism	1/17 (5.9%)		0/4 (0%)
Gastrointestinal disorders
Dental and gingival conditions	1/17 (5.9%)		1/4 (25%)
Diarrhea	2/17 (11.8%)		0/4 (0%)
Nausea and vomiting symptoms	1/17 (5.9%)		0/4 (0%)
Stomach ache	1/17 (5.9%)		0/4 (0%)
General disorders
Fatigue	2/17 (11.8%)		0/4 (0%)
Pyrexia	3/17 (17.6%)		0/4 (0%)
Immune system disorders
Allergic Rhinitis	1/17 (5.9%)		0/4 (0%)
Infections and infestations
Herpes simplex	2/17 (11.8%)		0/4 (0%)
Viral infection	1/17 (5.9%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Muscle pain	3/17 (17.6%)		0/4 (0%)
Joint ache	1/17 (5.9%)		0/4 (0%)
Arthralgia	1/17 (5.9%)		0/4 (0%)
Nervous system disorders
Headache	2/17 (11.8%)		1/4 (25%)
Psychiatric disorders
Adjustment disorder with mixed anxiety and depressed mood	1/17 (5.9%)		0/4 (0%)
Renal and urinary disorders
Renal colic	1/17 (5.9%)		0/4 (0%)
Urinary incontinence	1/17 (5.9%)		0/4 (0%)
Reproductive system and breast disorders
Dysmenorrhea	2/17 (11.8%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Tonsilllitis bacterial	1/17 (5.9%)		0/4 (0%)
Expectoration	2/17 (11.8%)		0/4 (0%)
Sore throat	1/17 (5.9%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Hair loss	1/17 (5.9%)		0/4 (0%)
Surgical and medical procedures
Open wound of knee, leg (except thigh), and ankle, without mention of complication	1/17 (5.9%)		0/4 (0%)
Vascular disorders
Hypertonia	1/17 (5.9%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.