Hepatitis B, Chronic
Conditions
Brief summary
This is an expanded access, multicenter, national, open-label, and non-randomized study to analyze the safety of peginterferon alfa-2a in participants with hepatitis B e antigen (HBeAg) positive and HBeAg negative chronic HBV infection. All participants will receive 48 weeks treatment of peginterferon alfa-2a monotherapy, followed by a 24 week treatment-free follow-up period.
Interventions
DRUGPeginterferon alfa-2a
180 mcg SC injection QW for 48 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Non-cirrhotic participants * Hepatitis B surface antigen (HBsAg) positive for at least 6 months * Hepatitis B surface antibody (anti-HBs) negative * Elevated serum alanine aminotransferase (ALT) greater than (\>) upper limit of normal (ULN) but less than or equal to (\</=) 10 times of ULN * HBeAg positive participants: HBV DNA \> 500,000 copies/mL, HBeAg negative participants: HBV DNA \>100,000 copies/mL by polymerase chain reaction (PCR) * Participants with chronic hepatitis B (CHB) who are treatment-naive * No previous antiviral treatment with interferon (IFN: standard or pegylated) or with a nucleoside analogue * For women of childbearing potential: negative urine or serum pregnancy test documented within the 24-hour period prior to the first dose of test drug. Willingness to use reliable contraception during the study and for 3 months after treatment completion
Exclusion criteria
* Previous antiviral or IFN-based therapy for CHB before enrolment * Pregnant or breast feeding women participants * Evidence of decompensated liver disease * Co-infection with active hepatitis A, hepatitis C, hepatitis D and/or human immunodeficiency virus (HIV) * History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis * Previous or current hepatocellular carcinoma * History of or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease * Alpha-fetoprotein levels of \>100 nanograms (ng)/mL * Severe psychiatric disease * History of a severe seizure disorder or current anticonvulsant use * History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the participant, in the opinion of the investigator, unsuitable for the study * Thyroid disease uncontrolled by prescribed medications * Evidence of severe retinopathy * Alcohol intake more than 3 standard drinks per day for men and 2 standard drinks per day for women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of HBeAg Positive Participants With Hepatitis B Virus-deoxy Ribonucleic Acid (HBV-DNA) Less Than (<) 100,000 Copies Per Milliliter (Copies/mL) | End of 24-weeks follow-up (Week 72) | HBV-DNA was assessed in plasma samples using quantitative Roche polymerase chain reaction (PCR) or Taqman tests. |
| Number of Participants With HBV-DNA <20,000 Copies/mL | End of 24-weeks follow-up (Week 72) | HBV-DNA was assessed in plasma samples using quantitative Roche PCR or Taqman tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HBV-DNA <400 Copies/mL | Week 48 (end of treatment) and Week 72 (end of follow-up) | HBV-DNA was assessed in plasma samples using quantitative Roche PCR or Taqman tests. |
| Number of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 48 (end of treatment) and Week 72 (end of follow-up) | 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). Both HBeAg positive and negative participants were HBsAg positive at baseline and absence of HBsAg (seroconversion) was analyzed. |
| Number of Participants With Normalization of Alanine Aminotransferase (ALT) Level | Week 48 (end of treatment) and Week 72 (end of follow-up) | ALT 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 level increases. Normal ALT level = less than upper limit of normal (40 units per liter). |
| Number of Participants With HBeAg Seroconversion | Week 48 (end of treatment) and Week 72 (end of follow-up) | HBeAg seroconversion for HBeAg positive participants was defined as the loss of HBeAg (a negative result for HBeAg) and the presence of anti-HBe (a positive result for anti-HBe). |
Countries
New Zealand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HBeAg Negative Participants HBeAg negative participants received peginterferon alfa-2a 180 mcg SC injection QW for 48 weeks followed by a 24 weeks treatment-free follow-up period. | 4 |
| HBeAg Positive Participants HBeAg positive participants received peginterferon alfa-2a 180 mcg SC injection QW for 48 weeks followed by a 24 weeks treatment-free follow-up period. | 20 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | HBeAg Negative Participants | HBeAg Positive Participants | Total |
|---|---|---|---|
| Age, Continuous | 43.25 years STANDARD_DEVIATION 5.75 | 31.57 years STANDARD_DEVIATION 9.43 | 33.52 years STANDARD_DEVIATION 9.88 |
| Gender Female | 0 Participants | 7 Participants | 7 Participants |
| Gender Male | 4 Participants | 13 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 7 / 20 |
| serious Total, serious adverse events | 1 / 4 | 0 / 20 |
Outcome results
Primary
Number of HBeAg Positive Participants With Hepatitis B Virus-deoxy Ribonucleic Acid (HBV-DNA) Less Than (<) 100,000 Copies Per Milliliter (Copies/mL)
HBV-DNA was assessed in plasma samples using quantitative Roche polymerase chain reaction (PCR) or Taqman tests.
Time frame: End of 24-weeks follow-up (Week 72)
Population: Intent-to-treat (ITT) population included all participants who received at least one dose of study medication and had one subsequent post baseline assessment. Here, number of participants analyzed signified those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HBeAg Positive Participants | Number of HBeAg Positive Participants With Hepatitis B Virus-deoxy Ribonucleic Acid (HBV-DNA) Less Than (<) 100,000 Copies Per Milliliter (Copies/mL) | 7 participants |
Primary
Number of Participants With HBV-DNA <20,000 Copies/mL
HBV-DNA was assessed in plasma samples using quantitative Roche PCR or Taqman tests.
Time frame: End of 24-weeks follow-up (Week 72)
Population: ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HBeAg Positive Participants | Number of Participants With HBV-DNA <20,000 Copies/mL | 0 participants |
| HBeAg Positive Participants | Number of Participants With HBV-DNA <20,000 Copies/mL | 3 participants |
Secondary
Number of Participants With HBeAg Seroconversion
HBeAg seroconversion for HBeAg positive participants was defined as the loss of HBeAg (a negative result for HBeAg) and the presence of anti-HBe (a positive result for anti-HBe).
Time frame: Week 48 (end of treatment) and Week 72 (end of follow-up)
Population: ITT population. Only HBeAg positive participants was planned to be reported. Here, number of participants analyzed signified those participants who were evaluable for this outcome and n signified participants with evaluable data for a specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HBeAg Positive Participants | Number of Participants With HBeAg Seroconversion | Week 48 (n=19) | 6 participants |
| HBeAg Positive Participants | Number of Participants With HBeAg Seroconversion | Week 72 (n=17) | 6 participants |
Secondary
Number of Participants With HBV-DNA <400 Copies/mL
HBV-DNA was assessed in plasma samples using quantitative Roche PCR or Taqman tests.
Time frame: Week 48 (end of treatment) and Week 72 (end of follow-up)
Population: ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and n signified participants with evaluable data for a specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HBeAg Positive Participants | Number of Participants With HBV-DNA <400 Copies/mL | Week 48 (n=4,18) | 3 participants |
| HBeAg Positive Participants | Number of Participants With HBV-DNA <400 Copies/mL | Week 72 (n=3,17) | 0 participants |
| HBeAg Positive Participants | Number of Participants With HBV-DNA <400 Copies/mL | Week 48 (n=4,18) | 6 participants |
| HBeAg Positive Participants | Number of Participants With HBV-DNA <400 Copies/mL | Week 72 (n=3,17) | 2 participants |
Secondary
Number 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). Both HBeAg positive and negative participants were HBsAg positive at baseline and absence of HBsAg (seroconversion) was analyzed.
Time frame: Week 48 (end of treatment) and Week 72 (end of follow-up)
Population: ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and n signified participants with evaluable data for a specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HBeAg Positive Participants | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 48 (n=4,15) | 0 participants |
| HBeAg Positive Participants | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 72 (n=4,13) | 0 participants |
| HBeAg Positive Participants | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 48 (n=4,15) | 0 participants |
| HBeAg Positive Participants | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion | Week 72 (n=4,13) | 0 participants |
Secondary
Number of Participants With Normalization of Alanine Aminotransferase (ALT) Level
ALT 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 level increases. Normal ALT level = less than upper limit of normal (40 units per liter).
Time frame: Week 48 (end of treatment) and Week 72 (end of follow-up)
Population: ITT population. Here, number of participants analyzed signified those participants who were evaluable for this outcome and n signified participants with evaluable data for a specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HBeAg Positive Participants | Number of Participants With Normalization of Alanine Aminotransferase (ALT) Level | Week 48 (n=4,19) | 2 participants |
| HBeAg Positive Participants | Number of Participants With Normalization of Alanine Aminotransferase (ALT) Level | Week 72 (n=4,17) | 4 participants |
| HBeAg Positive Participants | Number of Participants With Normalization of Alanine Aminotransferase (ALT) Level | Week 48 (n=4,19) | 4 participants |
| HBeAg Positive Participants | Number of Participants With Normalization of Alanine Aminotransferase (ALT) Level | Week 72 (n=4,17) | 7 participants |