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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01011738
First received: November 10, 2009
Last updated: March 10, 2016
Last verified: March 2016
  Purpose
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.

Condition
Hepatitis B, Chronic

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multicenter, Prospective, Observational, Non-Interventional Cohort Study Evaluating On-Treatment Predictors of Response in Subjects With HBeAg Positive and HBeAg Negative Chronic Hepatitis B Receiving Therapy With PEGASYS(R) (Peginterferon Alfa-2a 40KD)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Hepatitis B Virus Surface Antigen Clearance [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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:
  • Percentage of Participants With Suppression of Hepatitis B Virus Deoxyribonucleic Acid to <2,000 International Units Per Milliliter [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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 in Hepatitis B Virus e Antigen Positive Participants [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]

    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.


  • Percentage of Participants With Hepatitis B Surface Antigen Seroconversion [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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.

  • Quantitative Hepatitis B Surface Antigen [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Normalization of Alanine Transaminase [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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.

  • Alanine Transaminase Ratio Over Time by Hepatitis B Virus e Antigen Status [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    ALT ratio was calculated as serum ALT, divided by the upper limit of the normal range.

  • Number of Participants With Chronic Hepatitis B - Associated Clinical Endpoints- Liver Transplantation, Hepatocellular Carcinoma, and Liver Decompensation [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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).

  • Number of Participants With Chronic Hepatitis B Associated Clinical Endpoints- Liver Cirrhosis [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Serious Adverse Drug Reactions [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: Yes ]
    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 Participants With Non-Serious Adverse Drug Reactions [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: Yes ]
    Non serious adverse drug reactions (NSADRs) are all noxious and unintended responses to a medicinal product related to any dose.

  • Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Deaths During Observation Period [ Time Frame: Up to 276 Weeks ] [ Designated as safety issue: No ]
    The clinical endpoint of deaths due to any cause during observation period is presented.


Enrollment: 1842
Study Start Date: April 2009
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with chronic hepatitis C receiving treatment with peginterferon alfa-2a 40KD (Pegasys)
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • coinfection with HAV, HCV and HIV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011738

  Show 230 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01011738     History of Changes
Other Study ID Numbers: MV22009 
Study First Received: November 10, 2009
Results First Received: January 28, 2016
Last Updated: March 10, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 24, 2016