Hepatitis B, Chronic
Conditions
Brief summary
This is an expanded access programme to make Pegasys (peginterferon alfa-2a) available to patients with HBeAg-negative chronic hepatitis B in Morocco. Patients will receive Pegasys 180 mcg subcutaneously weekly for 48 weeks and efficacy and safety will be recorded during treatment and for 24 weeks of follow-up.
Interventions
DRUGPeginterferon alfa-2a [Pegasys]
180 mcg subcutaneously weekly, 48 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 and \</= 70 years of age * HBeAg-negative chronic hepatitis B * HBsAg-positive for at least 6 months, anti- hepatitis B (HBs) negative * Serum alanine transaminase (ALT) \> 2 ULN (upper limit of normal) but \</= 10 x Upper limit of normal (ULN) * Hepatitis B virus (HBV) DNA \> 10'000 copies/ml (Roche Monitor or Taqman) * No previous treatment with interferon (standard or pegylated) or with a nucleoside analogue * Women of childbearing potential must agree to use reliable contraception during the study and for 3 months after treatment completion
Exclusion criteria
* Previous antiviral interferon-based therapy for chronic hepatitis B * Pregnant and lactating women * 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 or other evidence of bleeding from oesophageal varices or other conditions consistent with decompensated liver disease * Inadequate hematologic or renal function * Serum bilirubin level \> 2 times the upper limit of normal * Severe psychiatric disease * History of severe seizure disorder or current anticonvulsant use * History of evidence of any disease or condition which would make the patient, in the opinion of the investigator, unsuitable for the study * Evidence of drug abuse within one year of study entry * Alcohol intake of more than 3 standard drinks per day for men and 2 standard drinks per day for women (1 standard drink contains 10 g of alcohol) * Participation in another trial or receipt of an investigational drug within 12 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hepatitis C Virus Deoxyribonucleic Acid <10,000 Copies/Milliliter at Week 72 | At Week 72 | Participants who had Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) levels below 100,000 copies per milliliter (mL) at the end of follow-up (at Week 72) were reported. |
| Percentage of Participants Achieving Normalization of Alanine Aminotransferase at Week 72 | At Week 72 | Percentage of participants with a normal serum alanine aminotransferase (ALT) level at the end of the study was analyzed. Normal ranges for ALT are 7 to 56 International Units/Litre. Participants with ALT less than the upper limit of normal at end of treatment were reported. |
| Number of Participants With Any Adverse Events and Serious Adverse Events | Up to Week 72 | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hepatitis B Virus DNA < 400 Copies/mL at Week 72 | At Week 72 | Participants who had HBV-DNA levels below 400 Copies/mL at the end of follow-up (at Week 72) were reported. |
| Percentage of Participants Achieving Hepatitis B Surface Antigen Seroconversion at Screening and Week 48 | At Screening and Week 48 | Seroconversion is defined as the absence of hepatitis B surface antigen (HBsAg) with a negative result for HBsAg and the presence of anti-Haemoglobin (HBs) antibodies (a positive result for anti-HBs) determined at Week 48. Blood samples were analyzed to check whether it is HBsAg-negative and anti-HBs antibodies positive. |
| Percentage of Participants Achieving Combined Response Hepatitis B Virus DNA < 10,000 Copies/mL and Normal ALT at Week 72 | At Week 72 | Percentage of participants showing normal ALT values and HBV DNA levels \<10,000 copies/ mL were reported. |
Countries
Morocco
Participant flow
Recruitment details
A total of 59 participants were enrolled in this study conducted from 13 January 2006 to 25 May 2009 at 9 centers in Kingdom of Morocco.
Participants by arm
| Arm | Count |
|---|---|
| Peginterferon Alpha-2a, 180 mcg/48 Weeks Eligible participants with HI3vAg (a type of hepatitis B surface antigen) negative chronic hepatitis B administered PEGASYS, 40kD, 180 mcg, subcutaneously once weekly for 48 weeks. The untreated follow-up was for 24 weeks. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 59 |
| serious Total, serious adverse events | 0 / 59 |
Outcome results
Primary
Number of Participants With Any Adverse Events and Serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above
Time frame: Up to Week 72
Population: Safety analysis population is defined to include only participants who receive at least one dose of study medication and have one subsequent post baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Number of Participants With Any Adverse Events and Serious Adverse Events | Any AE | 46 Participants |
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Number of Participants With Any Adverse Events and Serious Adverse Events | Any SAE | 0 Participants |
Primary
Percentage of Participants Achieving Hepatitis C Virus Deoxyribonucleic Acid <10,000 Copies/Milliliter at Week 72
Participants who had Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) levels below 100,000 copies per milliliter (mL) at the end of follow-up (at Week 72) were reported.
Time frame: At Week 72
Population: Intent-to-treat (ITT) population included all the participants who received at least one dose of study medication and had one subsequent post baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Hepatitis C Virus Deoxyribonucleic Acid <10,000 Copies/Milliliter at Week 72 | 65.4 Percentage of participants |
Primary
Percentage of Participants Achieving Normalization of Alanine Aminotransferase at Week 72
Percentage of participants with a normal serum alanine aminotransferase (ALT) level at the end of the study was analyzed. Normal ranges for ALT are 7 to 56 International Units/Litre. Participants with ALT less than the upper limit of normal at end of treatment were reported.
Time frame: At Week 72
Population: ITT population included all the participants who received at least one dose of study medication and had one subsequent post baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Normalization of Alanine Aminotransferase at Week 72 | 68.6 Percentage of participants |
Secondary
Percentage of Participants Achieving Combined Response Hepatitis B Virus DNA < 10,000 Copies/mL and Normal ALT at Week 72
Percentage of participants showing normal ALT values and HBV DNA levels \<10,000 copies/ mL were reported.
Time frame: At Week 72
Population: ITT population included all the participants who received at least one dose of study medication and had one subsequent post baseline assessment. Participants available at the time of assessment were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Combined Response Hepatitis B Virus DNA < 10,000 Copies/mL and Normal ALT at Week 72 | 58.8 Percentage of participants |
Secondary
Percentage of Participants Achieving Hepatitis B Surface Antigen Seroconversion at Screening and Week 48
Seroconversion is defined as the absence of hepatitis B surface antigen (HBsAg) with a negative result for HBsAg and the presence of anti-Haemoglobin (HBs) antibodies (a positive result for anti-HBs) determined at Week 48. Blood samples were analyzed to check whether it is HBsAg-negative and anti-HBs antibodies positive.
Time frame: At Screening and Week 48
Population: ITT population included all the participants who received at least one dose of study medication and had one subsequent post baseline assessment. 'n'=number of evaluable participants available at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Hepatitis B Surface Antigen Seroconversion at Screening and Week 48 | HBs-Ag Negative, Screening (n= 59) | 1.7 Percentage of participants |
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Hepatitis B Surface Antigen Seroconversion at Screening and Week 48 | HBs-Ag Negative, Week 48 (n= 55) | 10.9 Percentage of participants |
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Hepatitis B Surface Antigen Seroconversion at Screening and Week 48 | Anti-HBs Positive, Screening (n= 59) | 0 Percentage of participants |
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Hepatitis B Surface Antigen Seroconversion at Screening and Week 48 | Anti-HBs Positive, Week 48 (n= 55) | 10.9 Percentage of participants |
Secondary
Percentage of Participants Achieving Hepatitis B Virus DNA < 400 Copies/mL at Week 72
Participants who had HBV-DNA levels below 400 Copies/mL at the end of follow-up (at Week 72) were reported.
Time frame: At Week 72
Population: ITT population included all the participants who received at least one dose of study medication and had one subsequent post baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha-2a, 180 mcg/48 Weeks | Percentage of Participants Achieving Hepatitis B Virus DNA < 400 Copies/mL at Week 72 | 26.9 Percentage of participants |