Back to resultsA Study of Early Immunologic Response in Asian Patients With Chronic Hepatitis B, Treated With Pegasys (Peginterferon Alfa-2a (40KD)), Nucleoside Analogues, or Both
Primary Purpose
Hepatitis B, Chronic
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
peginterferon alfa-2a [Pegasys]
tenofovir
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B, Chronic
Eligibility Criteria
Inclusion Criteria:
- male adults of Southeast and/or East Asian origin, 18-55 years of age
- HBeAg-positive chronic hepatitis B
- detectable HBV DNA
Exclusion Criteria:
- prior antiviral therapy for chronic hepatitis B
- evidence of bridging fibrosis, cirrhosis or decompensated liver disease
- positive test at screening for HAV (IgM), HCV, HDV or HIV
- history or evidence of medical condition associated with chronic liver disease
- antineoplastic or immunomodulatory treatment </=6 months prior to first dose of study drug
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Experimental
No Intervention
Arm Label
1
2
3
4
Arm Description
Outcomes
Primary Outcome Measures
Mean Change From Baseline in Viral Quantitative e Antibody
An acute virologic response was determined by change from baseline in viral antigen/antibody laboratory data.
Secondary Outcome Measures
Mean Change From Baseline in HBV-DNA log10
An acute virologic response was determined by change from baseline in HBV-DNA log10.
Early Changes in Viral Sequence Associated With Viral Suppression
Viral sequence data was obtained from the first 10 participants enrolled in Study but on analysis of the data, numerous low frequency deviations from the HBV consensus sequences were observed in the 454 SLX sequence data which were not replicated in data obtained from routine Sanger sequencing. These sequence deviations did not correspond to a temporal pattern consistent with selection of mutations following HBV treatment. Moreover, they could not be reliably distinguished from sequencing artifacts. It was also revealed that complete genome coverage was not obtained due to errors in the design of the primer sequences. For these reasons, further sequence analyses were not performed for the remaining treatment population.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00962871
Brief Title
A Study of Early Immunologic Response in Asian Patients With Chronic Hepatitis B, Treated With Pegasys (Peginterferon Alfa-2a (40KD)), Nucleoside Analogues, or Both
Official Title
An Open-label, Randomized Study to Evaluate the Acute Immunologic Responses in Asian Subjects With E Antigen Positive Chronic Hepatitis B Following Initiation of Therapy for Hepatitis B With Pegasys, Nucleoside Analogues, or Both.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
August 2009 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This open-label, randomized, parallel-arm study will assess the early immunologic response in treatment-naïve Asian male patients with chronic hepatitis B after initiation of treatment with Pegasys or tenofovir or Pegasys plus tenofovir. Patients will be randomized to one of 4 cohorts to receive either Pegasys (360mcg subcutaneously weekly) or tenofovir (300mg orally daily) or both or no treatment for 2 weeks. After 2 weeks on study treatment, patients may opt to receive standard of care treatment with Pegasys. Target sample size is <50.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Title
2
Arm Type
Experimental
Arm Title
3
Arm Type
Experimental
Arm Title
4
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
peginterferon alfa-2a [Pegasys]
Intervention Description
360 micrograms sc/week for 2 weeks
Intervention Type
Drug
Intervention Name(s)
tenofovir
Intervention Description
300mg po daily for 2 weeks
Primary Outcome Measure Information:
Title
Mean Change From Baseline in Viral Quantitative e Antibody
Description
An acute virologic response was determined by change from baseline in viral antigen/antibody laboratory data.
Time Frame
Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys)
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in HBV-DNA log10
Description
An acute virologic response was determined by change from baseline in HBV-DNA log10.
Time Frame
Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys)
Title
Early Changes in Viral Sequence Associated With Viral Suppression
Description
Viral sequence data was obtained from the first 10 participants enrolled in Study but on analysis of the data, numerous low frequency deviations from the HBV consensus sequences were observed in the 454 SLX sequence data which were not replicated in data obtained from routine Sanger sequencing. These sequence deviations did not correspond to a temporal pattern consistent with selection of mutations following HBV treatment. Moreover, they could not be reliably distinguished from sequencing artifacts. It was also revealed that complete genome coverage was not obtained due to errors in the design of the primer sequences. For these reasons, further sequence analyses were not performed for the remaining treatment population.
Time Frame
Day 1, 5, 14, Week 4 and 6
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
male adults of Southeast and/or East Asian origin, 18-55 years of age
HBeAg-positive chronic hepatitis B
detectable HBV DNA
Exclusion Criteria:
prior antiviral therapy for chronic hepatitis B
evidence of bridging fibrosis, cirrhosis or decompensated liver disease
positive test at screening for HAV (IgM), HCV, HDV or HIV
history or evidence of medical condition associated with chronic liver disease
antineoplastic or immunomodulatory treatment </=6 months prior to first dose of study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90036
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0538
Country
United States
City
Grafton
ZIP/Postal Code
1010
Country
New Zealand
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
12. IPD Sharing Statement
Citations:
PubMed Identifier
32049318
Citation
Mehrotra A, D'Angelo JA, Romney-Vanterpool A, Chu T, Bertoletti A, Janssen HLA, Gehring AJ. IFN-alpha Suppresses Myeloid Cytokine Production, Impairing IL-12 Production and the Ability to Support T-Cell Proliferation. J Infect Dis. 2020 Jun 16;222(1):148-157. doi: 10.1093/infdis/jiaa064.
Results Reference
derived
PubMed Identifier
25406369
Citation
Hong LZ, Hong S, Wong HT, Aw PP, Cheng Y, Wilm A, de Sessions PF, Lim SG, Nagarajan N, Hibberd ML, Quake SR, Burkholder WF. BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads. Genome Biol. 2014;15(11):517. doi: 10.1186/PREACCEPT-6768001251451949.
Results Reference
derived
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/23994382
Description
This report describes the early effects of IFNα treatment on immune and viral biomarkers in HBeAg+ CHB patients. The results show that PegIFNα-induced innate immune activation directly benefits from the suppression of HBV replication.
Learn more about this trial
A Study of Early Immunologic Response in Asian Patients With Chronic Hepatitis B, Treated With Pegasys (Peginterferon Alfa-2a (40KD)), Nucleoside Analogues, or Both
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