An Observational Cohort Study in Patients With Chronic Hepatitis B Receiving Pegasys

Completed

Conditions: Hepatitis B, Chronic

Registration Number: NCT01011738

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This observational, non-interventional cohort study will evaluate predictors of response in patients with chronic hepatitis B receiving standard of care Pegasys therapy. Efficacy and safety parameters will also be evaluated. Patients included in the study will be followed for the duration of their treatment and for up to 3 years thereafter.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1842

Inclusion Criteria

adult patient, >/= 18 years of age
chronic hepatitis B
treatment with peginterferon alfa-2A

Exclusion Criteria

coinfection with HAV, HCV and HIV

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Hepatitis B Virus Surface Antigen Clearance	Up to 276 Weeks	Percentage of participants who became Hepatitis B Virus Surface Antigen (HBsAg) negative by the end of the observation period. A participant was considered to have achieved HBsAg clearance if the HBsAg measurement was reported as: (a) 'Negative' or (b) a quantitative result lower than the reported lower limit of detection. An observational period was upto 3 years post-treatment. The analysis was performed by 2 methods: Analysis A and Analysis B. For analysis A, all participants included in the analyzed population were used (participants with missing measurement for calculation of the endpoint were considered non-responders regarding the endpoint). For analysis B method, only participants in the analyzed population without missing measurements for calculation of the endpoint were used (analysis "as observed").
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Positive Participants	Up to 276 Weeks	The probability that the participant who develops an early virological/serological response would achieve Hepatitis B Surface Antigen (HBsAg) clearance 3 years post-treatment is called the positive predictive value (PPV) of the early virological/serological response. The probability that the participant who fails to develop an early virological/serological response also would fail to achieve HBsAg clearance 3 years post-treatment is called the negative predictive value (NPV) of the early virological/serological response. The positive and negative predictive values of early response at Weeks 12 and 24 on achievement of HBsAg clearance at 3 years post-treatment were examined. The following evidence of early response was explored (giving both NPV and PPV): For HBeAg positive participant, HBsAg \<1,500 International Units Per Milliliter (IU/mL) and HBsAg \<20,000 IU/mL at Weeks 12 and 24.
Predictive Values of Early on Treatment Response for Hepatitis B Surface Antigen Clearance 3 Years Post-Treatment- Hepatitis B Virus e Antigen Negative Participants	Up to 276 Weeks	The probability that the participant who develops an early virological/serological response would achieve HBsAg clearance 3 years post-treatment is called the PPV of the early virological/serological response. The probability that the participant who fails to develop an early virological/serological response also would fail to achieve HBsAg clearance 3 years post-treatment is called the NPV of the early virological/serological response. The positive and negative predictive values of early response at Weeks 12 and 24 on achievement of HBsAg clearance at 3 years post-treatment were examined. The following evidence of early response was explored (giving both NPV and PPV): For HBeAg negative patients, any decline in HBsAg from baseline to Week 12 and 24 and at least a 10% decline in HBsAg from baseline to Weeks 12 and 24.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Non-Serious Adverse Drug Reactions	Up to 276 Weeks	Non serious adverse drug reactions (NSADRs) are all noxious and unintended responses to a medicinal product related to any dose.
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion in Hepatitis B Virus e Antigen Positive Participants	Up to 276 Weeks	HBeAg seroconversion is presented as percentage of participants who become HBeAg negative and anti-HBe positive. A participant was considered to have achieved HBeAg seroconversion if (a) the participant achieved HBeAg loss and (b) the anti-HBe measurement was reported as (i) 'POSITIVE' or (ii) a quantitative result considered 'positive' in the context. HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL: A participant was considered to have achieved HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL if (a) the participant achieved HBeAg seroconversion and (b) the participant achieved suppression of HBV DNA to \<2,000 IU/mL. Abbreviations for pt=post-treatment.
Percentage of Participants With Hepatitis B Virus e Antigen Loss in Hepatitis B Virus e Antigen Positive Participants	Up to 276 Weeks	A participant was considered to have achieved HBeAg loss if the HBeAg measurement was reported as (a) 'NEGATIVE' or (b) a quantitative result was lower than the reported lower detection limit. This endpoint was measured in the participants with HBeAg positive CHB.
Quantitative Hepatitis B Surface Antigen	Up to 276 Weeks	Quantitative HBsAg assay is a diagnostic test for assessing the amount of the HBsAg in chronic hepatitis B participants. Last approved quantitative HBsAg measurement in the analyzed time window.
Number of Participants With Chronic Hepatitis B - Associated Clinical Endpoints- Liver Transplantation, Hepatocellular Carcinoma, and Liver Decompensation	Up to 276 Weeks	Number of clinical endpoints associated with CHB reported in the medical record, where data available, are reported. The clinical endpoints included liver transplantation, hepatocellular carcinoma, liver decompensation, development of cirrhosis (in patients without cirrhosis at baseline).
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion	Up to 276 Weeks	Hepatitis B surface antigen (HBsAg) is a viral protein detectable in the blood in acute and chronic hepatitis B infection. A participant was considered to have achieved HBsAg seroconversion if (a) the participant achieved HBsAg clearance and (b) the last approved anti-HBs measurement in the analyzed time window was reported as i) 'POSITIVE' or (ii) quantitative result and was greater than or equal to the reported lower limit of detection.
Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status	Up to 276 Weeks	ALT ratio was calculated as serum ALT, divided by the upper limit of the normal range.
Number of Participants With Adverse Events and Serious Adverse Events	Up to 276 Weeks	An Adverse Events (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes.
Percentage of Participants With Normalization of Alanine Transaminase	Up to 276 Weeks	A participant was considered to have achieved normalization of alanine transaminase (ALT) if the ALT measurement was lower or equal to the upper limit of the normal range. Only patients with elevated ALT at baseline were included in any analyses where normalization of ALT was used as endpoint. It was analyzed as last serum ALT in the analyzed time window, divided by the upper limit of the normal range.
Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis	Up to 276 Weeks	Number of participants with clinical endpoints associated with CHB captured in the medical record, where data available, are reported. The clinical endpoints included development of cirrhosis (in participants without cirrhosis at baseline). The liver cirrhosis assessments were summarized from Week 12 to 3 years post-treatment.
Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter	Up to 276 Weeks	A participant was considered to have achieved suppression of Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) to \<2,000 International Units Per Milliliter (IU/mL) if the HBV DNA measurement is lower than 2,000 IU/mL.
Percentage of Participants With Hepatitis B Virus e Antigen Seroconversion and Hepatitis B Virus Deoxyribonucleic Acid <2000IU/mL in Hepatitis B Virus e Antigen Positive Participants	Up to 276 Weeks	A participant was considered to have achieved HBeAg seroconversion and suppression of HBV DNA to \<2,000 IU/mL if (a) the participant achieved HBeAg seroconversion and (b) the participant achieved suppression of HBV DNA to \<2,000 IU/mL. If a patient received NUCs after end of PEG IFN treatment, then a reported suppression of HBV DNA to \< 2,000 IU/mL during or after this NUC treatment were to be ignored, and HBV DNA ≥ 2,000 IU/mL was to be assigned. However, HBV DNA \< 2,000 IU/mL was not to be ignored, if the NUC treatment given parallel to PEG IFN was discontinued within the first 8 weeks after end of PEG IFN treatment and prior to the HBV DNA value concerned no further NUCs were administered. Abbreviations for Seroconversion=sercnvrsn, Analysis A= AnalysA, and Analysis B= AnalysB, pt=post-treatment.
Number of Participants With Serious Adverse Drug Reactions	Up to 276 Weeks	A serious adverse drug reactions (SADR) is any untoward medical occurrence suspected to be medicinal product-related that at any dose: Results in death, is life-threatening, NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or Is a congenital anomaly/birth defect.
Number of Deaths During Observation Period	Up to 276 Weeks	The clinical endpoint of deaths due to any cause during observation period is presented.

Trial Locations

Locations (249): Lkh-Univ. Klinikum Graz
🇦🇹
Graz, Austria
Tiroler Landeskrankenanstalten Ges.M.B.H.; Klinische Abt. Für Gaströnterologie & Hepatologie
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Innsbruck, Austria
A.Ö. Krankenhaus Der Elisabethinen Linz; Iv. Med. Abtl.
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Linz, Austria
Medizinische Universität Wien; Univ.Klinik für Innere Medizin III - Gastroenterologie & Hepatologie
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Wien, Austria
Wilhelminenspital; Iv. Medizinische Abt.
🇦🇹
Wien, Austria
Salmaniya Medical Complex; Gastroenterology
🇧🇭
Manama, Bahrain
Liver Clinic Lab-Aid Specialized Hospital
🇧🇩
Dhaka, Bangladesh
The Liver Centre
🇧🇩
Dhaka, Bangladesh
Clinical Center Banja Luka; Department for Infective Diseases
🇧🇦
Banja Luka, Bosnia and Herzegovina
Cantonal Hospital Bihac; Department for Infective Diseses
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Bihac, Bosnia and Herzegovina
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Lkh-Univ. Klinikum Graz
🇦🇹Graz, Austria