An Expanded Access Study of Pegasys (Peginterferon Alfa-2a) in Patients With HBeAg-Negative Chronic Hepatitis B
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Peginterferon alpha-2a, 180 mcg/48 weeks Eligible participants with HI3vAg (a type of Hepatitis B surface antigen) negative chronic hepatitis B will be administered peginterferon alpha-2a (PEGASYS), 40kD, 180 micrograms (mcg) subcutaneously once weekly for 48 weeks. The untreated Follow-up will be for 24 weeks. |
Drug: Peginterferon alfa-2a [Pegasys]
180 mcg subcutaneously weekly, 48 weeks
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Casablanca | Morocco | 20100 | ||
| 2 | Casablanca | Morocco | |||
| 3 | Rabat | Morocco | 504 | ||
| 4 | Rabat | Morocco | 62000 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ML19522
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | Eligible participants with HI3vAg (a type of hepatitis B surface antigen) negative chronic hepatitis B administered peg interferon alpha-2a (PEGASYS), 40 kilodalton (kD), 180 micrograms (mcg), subcutaneously, once weekly for 48 weeks. The untreated follow-up was for 24 weeks. |
| Period Title: Overall Study | |
| STARTED | 59 |
| COMPLETED | 56 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 59 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
41
(11)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
20.3%
|
| Male |
47
79.7%
|
Outcome Measures
| Title | Percentage of Participants Achieving Hepatitis C Virus Deoxyribonucleic Acid <10,000 Copies/Milliliter at Week 72 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 59 |
| Number (95% Confidence Interval) [Percentage of participants] |
65.4
110.8%
|
| Title | Percentage of Participants Achieving Normalization of Alanine Aminotransferase at Week 72 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all the participants who received at least one dose of study medication and had one subsequent post baseline assessment. |
| Arm/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 59 |
| Number (95% Confidence Interval) [Percentage of participants] |
68.6
116.3%
|
| Title | Number of Participants With Any Adverse Events and Serious Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 59 |
| Any AE |
46
78%
|
| Any SAE |
0
0%
|
| Title | Percentage of Participants Achieving Hepatitis B Virus DNA < 400 Copies/mL at Week 72 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all the participants who received at least one dose of study medication and had one subsequent post baseline assessment. |
| Arm/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 59 |
| Number (95% Confidence Interval) [Percentage of participants] |
26.9
45.6%
|
| Title | Percentage of Participants Achieving Hepatitis B Surface Antigen Seroconversion at Screening and Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 59 |
| HBs-Ag Negative, Screening (n= 59) |
1.7
2.9%
|
| HBs-Ag Negative, Week 48 (n= 55) |
10.9
18.5%
|
| Anti-HBs Positive, Screening (n= 59) |
0
0%
|
| Anti-HBs Positive, Week 48 (n= 55) |
10.9
18.5%
|
| Title | Percentage of Participants Achieving Combined Response Hepatitis B Virus DNA < 10,000 Copies/mL and Normal ALT at Week 72 |
|---|---|
| Description | Percentage of participants showing normal ALT values and HBV DNA levels <10,000 copies/ mL were reported. |
| Time Frame | At Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Peginterferon Alpha-2a, 180 mcg/48 Weeks |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 51 |
| Number [Percentage of participants] |
58.8
99.7%
|
Adverse Events
| Time Frame | Up to Week 72 | |
|---|---|---|
| Adverse Event Reporting Description | An AE is any untoward medical occurrence in a participant or clinical investigation that does not necessarily have to have a causal relationship with treatment. An AE can be unfavourable and unintended sign, symptom, or disease associated with a medicinal product, whether or not considered related to the medicinal product. | |
| Arm/Group Title | Peginterferon Alpha-2a, 180 mcg/ 48 Weeks | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Peginterferon Alpha-2a, 180 mcg/ 48 Weeks | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Peginterferon Alpha-2a, 180 mcg/ 48 Weeks | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/59 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Peginterferon Alpha-2a, 180 mcg/ 48 Weeks | ||
| Affected / at Risk (%) | # Events | |
| Total | 40/59 (67.8%) | |
| Blood and lymphatic system disorders | ||
| Neutropenia | 9/59 (15.3%) | |
| General disorders | ||
| Asthenia | 23/59 (39%) | |
| Arthralgia | 4/59 (6.8%) | |
| Musculoskeletal and connective tissue disorders | ||
| Myalgia | 4/59 (6.8%) | |
| Psychiatric disorders | ||
| Anxiety | 5/59 (8.5%) | |
| Insomnia | 7/59 (11.9%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights
Results Point of Contact
| Name/Title | Roche Trial Information Hotline |
|---|---|
| Organization | F. Hoffmann-La Roche AG |
| Phone | +41 616878333 |
| global.trial_information@roche.com |
- ML19522