Trial Outcomes & Findings for 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). (NCT NCT00442572)

Last Updated: 2025-04-24

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

Up to Week 108

Results posted on

2025-04-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	PEGASYS 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.	No Intervention Participants were on non- specific anti-viral treatment.
Overall Study STARTED	17	4
Overall Study COMPLETED	9	1
Overall Study NOT COMPLETED	8	3

Reasons for withdrawal

Reasons for withdrawal
Measure	PEGASYS 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.	No Intervention Participants were on non- specific anti-viral treatment.
Overall Study Relapse	8	1
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PEGASYS n=17 Participants 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.	No Intervention n=4 Participants Participants were on non- specific anti-viral treatment.	Total n=21 Participants Total of all reporting groups
Age, Continuous	44 years n=39 Participants	38.5 years n=41 Participants	42 years n=35 Participants
Sex: Female, Male Female	7 Participants n=39 Participants	0 Participants n=41 Participants	7 Participants n=35 Participants
Sex: Female, Male Male	10 Participants n=39 Participants	4 Participants n=41 Participants	14 Participants n=35 Participants

PRIMARY outcome

Timeframe: Up to Week 108

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

Outcome measures

Outcome measures
Measure	PEGASYS n=17 Participants 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..	No Intervention n=3 Participants Participants were on non- specific anti-viral treatment.
Percentage of Participants With Stable Virological Response Week 12	100 Percentage of Participants Interval 80.49 to 100.0	100.0 Percentage of Participants Interval 29.24 to 100.0
Percentage of Participants With Stable Virological Response Week 24	52.9 Percentage of Participants Interval 27.81 to 77.02	66.7 Percentage of Participants Interval 9.42 to 99.16
Percentage of Participants With Stable Virological Response Week 36	52.9 Percentage of Participants Interval 27.81 to 77.02	100.0 Percentage of Participants Interval 29.24 to 100.0
Percentage of Participants With Stable Virological Response Week 48	47.1 Percentage of Participants Interval 22.98 to 72.19	66.7 Percentage of Participants Interval 9.42 to 99.16
Percentage of Participants With Stable Virological Response Week 60	47.1 Percentage of Participants Interval 22.98 to 72.19	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological Response Week 72	41.2 Percentage of Participants Interval 18.44 to 67.08	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological Response Week 84	41.2 Percentage of Participants Interval 18.44 to 67.08	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological Response Week 96	29.4 Percentage of Participants Interval 10.31 to 55.96	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological Response Week 108	29.4 Percentage of Participants Interval 10.31 to 55.96	33.3 Percentage of Participants Interval 0.84 to 90.58

SECONDARY outcome

Timeframe: Up to Week 108

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

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).

Outcome measures

Outcome measures
Measure	PEGASYS n=17 Participants 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..	No Intervention n=3 Participants Participants were on non- specific anti-viral treatment.
Percentage of Participants With Stable Virological and Biochemical Response Week 12	100.0 Percentage of Participants Interval 80.49 to 100.0	100.0 Percentage of Participants Interval 29.24 to 100.0
Percentage of Participants With Stable Virological and Biochemical Response Week 24	52.9 Percentage of Participants Interval 27.81 to 77.02	66.7 Percentage of Participants Interval 9.42 to 99.16
Percentage of Participants With Stable Virological and Biochemical Response Week 36	52.9 Percentage of Participants Interval 27.81 to 77.02	100.0 Percentage of Participants Interval 29.24 to 100.0
Percentage of Participants With Stable Virological and Biochemical Response Week 48	47.1 Percentage of Participants Interval 22.98 to 72.19	66.7 Percentage of Participants Interval 9.42 to 99.16
Percentage of Participants With Stable Virological and Biochemical Response Week 60	47.1 Percentage of Participants Interval 22.98 to 72.19	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological and Biochemical Response Week 96	29.4 Percentage of Participants Interval 10.31 to 55.96	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological and Biochemical Response Week 108	29.4 Percentage of Participants Interval 10.31 to 55.96	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological and Biochemical Response Week 72	41.2 Percentage of Participants Interval 18.44 to 67.08	33.3 Percentage of Participants Interval 0.84 to 90.58
Percentage of Participants With Stable Virological and Biochemical Response Week 84	41.2 Percentage of Participants Interval 18.44 to 67.08	33.3 Percentage of Participants Interval 0.84 to 90.58

SECONDARY outcome

Timeframe: Up to Week 108

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

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

Outcome measures

Outcome measures
Measure	PEGASYS n=17 Participants 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..	No Intervention n=3 Participants Participants were on non- specific anti-viral treatment.
Percentage of Participants With Loss of Hepatitis B Surface Antigen	5.9 Percentage of Participants Interval 0.14 to 28.69	0 Percentage of Participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Up to Week 108

Population: 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.

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).

Outcome measures

Outcome measures
Measure	PEGASYS n=1 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Percentage of Participants With HBsAg Seroconversion	0 Percentage of Participants	—

SECONDARY outcome

Timeframe: Up to Week 108

Population: 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.

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.

Outcome measures

Outcome measures
Measure	PEGASYS n=17 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Percentage of Participants With HBV DNA Levels Under the Lower Limit (Serum HBV DNA Level < 300 Copies/ml) For a Significant Quantity	29.4 Percentage of Participants Interval 10.3 to 56.0	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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.

Outcome measures

Outcome measures
Measure	PEGASYS n=13 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index Scores For Change in Liver Fibrosis FIB-4	1.06 Units on a scale Interval 0.36 to 2.66	—
Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index Scores For Change in Liver Fibrosis APRI	0.25 Units on a scale Interval 0.14 to 1.48	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PEGASYS n=17 Participants 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..	No Intervention n=3 Participants Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in HBsAg Levels Week 96, n=14,1	-3011.75 copies/mL Interval -8046.71 to 2023.21	-49.51 copies/mL For Week 96, only one participant had valid data based on which 95% CI cannot be constructed.
Mean Change From Baseline in HBsAg Levels Week 12, n=17,3	-1156.00 copies/mL Interval -5212.33 to 2900.33	-240.50 copies/mL Interval -3715.65 to 3234.65
Mean Change From Baseline in HBsAg Levels Week 24, n=17,3	-1293.72 copies/mL Interval -5756.89 to 3169.45	-146.00 copies/mL Interval -7172.53 to 6880.53
Mean Change From Baseline in HBsAg Levels Week 36, n=14,3	-3049.64 copies/mL Interval -7949.3 to 1850.01	-564.00 copies/mL Interval -4248.8 to 3120.8
Mean Change From Baseline in HBsAg Levels Week 48, n=13, 3	-1591.78 copies/mL Interval -9217.83 to 6034.28	-528.50 copies/mL Interval -2987.15 to 1930.15
Mean Change From Baseline in HBsAg Levels Week 60, n=11,1	-3096.56 copies/mL Interval -11135.37 to 4942.26	-379.00 copies/mL For Week 60, only one participant had valid data based on which 95% CI cannot be constructed.
Mean Change From Baseline in HBsAg Levels Week 72, n=10, 1	-3485.90 copies/mL Interval -10299.06 to 3327.26	-34.00 copies/mL For Week 72, only one participant had valid data based on which 95% CI cannot be constructed.
Mean Change From Baseline in HBsAg Levels Week 84, n=9, 1	201.40 copies/mL Interval -11899.81 to 12302.61	-54.72 copies/mL For Week 84, only one participant had valid data based on which 95% CI cannot be constructed.
Mean Change From Baseline in HBsAg Levels Week 108, n=12,0	-3368.13 copies/mL Interval -7625.12 to 888.87	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Hemoglobin	-1.73 Gram/deciliter Standard Deviation 10.44	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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).

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Hematology Erythrocytes	0.08 10^9/L Standard Deviation 0.26	—
Mean Change From Baseline in Hematology Leukocytes	-1.72 10^9/L Standard Deviation 2.00	—
Mean Change From Baseline in Hematology Basophils	-0.18 10^9/L Standard Deviation 0.38	—
Mean Change From Baseline in Hematology Lymphocytes	5.56 10^9/L Standard Deviation 6.31	—
Mean Change From Baseline in Hematology Monocytes	1.87 10^9/L Standard Deviation 3.10	—
Mean Change From Baseline in Hematology Thrombocytes	-31.20 10^9/L Standard Deviation 36.40	—
Mean Change From Baseline in Hematology Eosinophils	0.92 10^9/L Standard Deviation 1.24	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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).

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Clinical Chemistry ALAT	5.56 Units/Litre Standard Deviation 25.44	—
Mean Change From Baseline in Clinical Chemistry ASAT	9.00 Units/Litre Standard Deviation 27.76	—
Mean Change From Baseline in Clinical Chemistry GGT	1.00 Units/Litre Standard Deviation 3.70	—
Mean Change From Baseline in Clinical Chemistry ALP	50.92 Units/Litre Standard Deviation 38.00	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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).

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Protein and Indirect Albumin Protein indirect	-31.62 Gram/deciliter Standard Deviation 38.70	—
Mean Change From Baseline in Protein and Indirect Albumin Albumin	-1.35 Gram/deciliter Standard Deviation 1.71	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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).

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Bilirubin Indirect and Bilirubin Direct Indirect bilirubin	-0.95 milligrams/deciliter Standard Deviation 3.38	—
Mean Change From Baseline in Bilirubin Indirect and Bilirubin Direct Direct bilirubin	-0.16 milligrams/deciliter Standard Deviation 0.77	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Blood Urea	-0.34 millimoles/liter Standard Deviation 1.23	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Creatinine and Uric Acid Creatinine	-3.65 micromole/liter Standard Deviation 13.23	—
Mean Change From Baseline in Creatinine and Uric Acid Uric acid	-21.51 micromole/liter Standard Deviation 130.42	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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).

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Blood Glucose	-0.06 millimoles/ liter Standard Deviation 0.40	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Thyroid Stimulating Hormone (TSH)	0.67 milli-international units/liter Standard Deviation 1.50	—

SECONDARY outcome

Timeframe: Up to Week 108

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

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

Outcome measures

Outcome measures
Measure	PEGASYS n=12 Participants 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..	No Intervention Participants were on non- specific anti-viral treatment.
Mean Change From Baseline in Triiodothyronine and Thyroxine T4, Week 108	-0.85 picomole/liter Standard Deviation 4.99	—
Mean Change From Baseline in Triiodothyronine and Thyroxine T3, Week 108	0.19 picomole/liter Standard Deviation 5.44	—

Adverse Events

PEGASYS

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

No Intervention

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	PEGASYS n=17 participants at risk 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.	No Intervention n=4 participants at risk Participants were on non- specific anti-viral treatment.
Musculoskeletal and connective tissue disorders Muscle pain	17.6% 3/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Musculoskeletal and connective tissue disorders Joint ache	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Psychiatric disorders Adjustment disorder with mixed anxiety and depressed mood	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Immune system disorders Allergic Rhinitis	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Respiratory, thoracic and mediastinal disorders Tonsilllitis bacterial	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Gastrointestinal disorders Dental and gingival conditions	5.9% 1/17 • Up to Week 108 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.	25.0% 1/4 • Up to Week 108 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.
Gastrointestinal disorders Diarrhea	11.8% 2/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Reproductive system and breast disorders Dysmenorrhea	11.8% 2/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Respiratory, thoracic and mediastinal disorders Expectoration	11.8% 2/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
General disorders Fatigue	11.8% 2/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Skin and subcutaneous tissue disorders Hair loss	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Nervous system disorders Headache	11.8% 2/17 • Up to Week 108 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.	25.0% 1/4 • Up to Week 108 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.
Infections and infestations Herpes simplex	11.8% 2/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Vascular disorders Hypertonia	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Endocrine disorders Hypothyroidism	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Gastrointestinal disorders Nausea and vomiting symptoms	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Surgical and medical procedures Open wound of knee, leg (except thigh), and ankle, without mention of complication	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
General disorders Pyrexia	17.6% 3/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Renal and urinary disorders Renal colic	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Respiratory, thoracic and mediastinal disorders Sore throat	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Gastrointestinal disorders Stomach ache	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Renal and urinary disorders Urinary incontinence	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.
Infections and infestations Viral infection	5.9% 1/17 • Up to Week 108 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.	0.00% 0/4 • Up to Week 108 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.