A Follow-Up Study to WV19432, to Evaluate Long Term Post-Treatment Effects of PEGASYS (Peginterferon Alfa-2a(40KD))in Patients With HBeAg Positive Chronic Hepatitis B

Study Overview
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Brief Summary
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This study is a long-term post-treatment follow-up to study WV19432, which evaluated the efficacy and safety of PEGASYS in patients with HBeAg positive chronic hepatitis B (CHB).Patients who received treatment with PEGASYS, and completed follow-up, are eligible to enter this post-treatment follow-up study. The anticipated time on study was 5 years, and the target sample size is 100-500 individuals.

Official Title
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A Follow-up Study to Evaluate the Long-term Post Treatment Effects of Peginterferon Alfa-2a (PEG-IFN) in Patients With HBeAg Positive Chronic Hepatitis B From the Original Study WV19432(NEPTUNE).

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: peginterferon alfa-2a [Pegasys]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent for Study WV19432 Patients who have completed treatment and follow-up on study WV19432 Exclusion Criteria: As for Study WV19432

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-IFN 90mcg 24 Wks<br>Participants received Pegasys (Pegylated interferon alfa-2a [PEG-IFN]) 90 micrograms (mcg) subcutaneously (SC) once a week for 24 weeks in Study WV19432 and entered follow-up (FU) Study MV22430. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms/week sc for 24 or 48 weeks in original study (WV19432). No study treatment in long-term post-treatment follow-up study (MV22430)<br>|
| Experimental: PEG-IFN 180mcg 24 Wks<br>Participants received PEG-IFN 180 mcg SC once a week for 24 weeks in Study WV19432 and entered FU Study MV22430. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms/week sc for 24 or 48 weeks in original study (WV19432). No study treatment in long-term post-treatment follow-up study (MV22430)<br>|
| Experimental: PEG-IFN 90mcg 48 Wks<br>Participants received PEG-IFN 90 mcg SC once a week for 48 weeks in Study WV19432 and entered FU Study MV22430. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms/week sc for 24 or 48 weeks in original study (WV19432). No study treatment in long-term post-treatment follow-up study (MV22430)<br>|
| Experimental: PEG-IFN 180mcg 48 Wks<br>Participants received PEG-IFN 180 mcg SC once a week for 48 weeks in Study WV19432 and entered FU Study MV22430. | Drug: peginterferon alfa-2a [Pegasys]<br>* 90 or 180 micrograms/week sc for 24 or 48 weeks in original study (WV19432). No study treatment in long-term post-treatment follow-up study (MV22430)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Seroconversion. | HBeAg seroconversion was defined as the absence of HBeAg (a negative result for HBeAg) and the presence of anti-HBe (a positive result for anti-HBe). Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With HBsAg Loss | HBsAg loss is defined as the absence of HBsAg (i.e. a negative result for HBsAg). Missing values were counted as non-response. | Annually, for up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HBeAg Loss. | HBeAg loss is defined as the absence of HBeAg (i.e. a negative result for HBeAg). Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion. | HBsAg seroconversion was defined as the absence of HBsAg (a negative result for HBsAg) and the presence of anti-HBs (a positive result for anti-HBs). Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With Presence of Anti-Hepatitis B Envelope Antigen (HBe). | The presence of anti-HBe is defined as antibody produced against e antigen in HBeAg. Seroconversion from e antigen to e antibody (anti-HBe) is a predictor of long-term clearance of hepatitis B virus (HBV) in participants undergoing antiviral therapy and indicates lower levels of HBV, and therefore lower infectivity. Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With Presence of Anti-HBs | The presence of anti-HBs is defined as antibody produced against HBsAg.It is generally interpreted as indicating recovery and immunity from HBV infection. Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With Normalised Alanine Transaminase (ALT) | Alanine Transaminase is an enzyme found mainly in liver and is measured to check if the liver is damaged or diseased. In case of liver damage or disease, the liver releases ALT into the blood stream and the ALT levels increase. Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) Suppression < 20,000 International Unit/Milliliter (IU/mL). | The percentage of participants with HBV-DNA suppression < 20,000 IU/mL. HBV DNA is the genetic material that carries the blueprint of the virus. The measure of HBV DNA in blood indicates how rapidly the virus is replicating in liver. Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) Suppression < 2,000 International Unit/Milliliter (IU/mL) | The percentage of participants with HBV-DNA suppression < 2,000 IU/mL. HBV DNA is the genetic material that carries the blueprint of the virus. The measure of HBV DNA in blood indicates how rapidly the virus is replicating in liver. Missing values were counted as non-response. | Annually, for up to 5 years | 
| Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) Suppression < 80 International Unit/Milliliter (IU/mL) | The percentage of participants with HBV-DNA suppression < 80 IU/mL. HBV DNA is the genetic material that carries the blueprint of the virus. The measure of HBV DNA in blood indicates how rapidly the virus is replicating in liver. Missing values were counted as non-response. | Annually, for up to 5 years | 
| Quantitative HBsAg | Quantitative HBsAg assay is a diagnostic test for assessing the amount of the HBsAg in chronic Hepatitis B participants. Missing values were counted as non-response. | Annually, for up to 5 years | 
| Number of Participants Who Received Treatment With Antiviral, Immunomodulatory, Anti-inflammatory or Herbal/Botanical/Other Treatments for Chronic Hepatitis B | Participants who required additional treatments specifically to treat CHB, associated laboratory test abnormalities and associated symptoms in this long-term observation in the study were reported. Receipt of such treatment did not require participant withdrawal from further participation. | Up to 5-year FU period | 
| Number of Participants With Clinically Significant Events Related to Chronic Hepatitis B (CHB) | Clinically significant events were defined as one or more of the following: Hepatocellular carcinoma, hepatic decompensation, CHB-related death, hepatic transplant, marked elevation of serum ALT of >10 x upper limit of normal (ULN). | Up to 5-year FU period | 
| Number of Participants With Marked Laboratory Abnormalities | Marked abnormality of laboratory parameters is defined as the value which is outside the defined reference range of that respective parameter. Roche's following reference ranges for laboratory test parameters were used for the analysis: Hemoglobin (reference range: 110-200 grams/liter[g/L]), White blood cells (WBC) (3.0-18.0 ^10^9/L), Platelets (100-550 ^10^9/L), Neutrophils (1.50-9.25 ^10^9/L), Prothrombin time (PT) Normal ratio (n.d.-2.00), Alkaline phosphatase (0-220 units/liter [U/L]), Alanine aminotransferase (0-110 U/L), Aspartate transaminase (0-80 U/L), Total bilirubin (0-34 micromole/liter [umol/L]), Gamma-glutamyl transpeptidase (GGT) (0-190 U/L), Blood urea nitrogen (BUN) (0.0-14.3 millimole/liter [mmol/L]), Creatinine (0-154 umol/L), Total Protein (55-87 g/L), Albumin (30.0-n.d. g/L), Potassium (2.9-5.8 mmol/L), Sodium (130-150 mmol/L), Calcium (2.00-2.90 mmol/L), Uric acid (0-600 umol/L). It includes marked abnormalities observed during Study WV19432 and FU study MV22430 | Up to 5-year FU period |