Chronic Hepatitis BPhase 3NCT00221286
Efficacy and Safety of PegIFN +/- FTC / TDF to Treat Chronic Hepatitis B in HIV-Coinfected Patients
A Phase 3 study testing pegylated interferon alfa-2a, tenofovir DF / emtricitabine combination therapy and pegIFN / TDF / FTC combination therapy in people with Chronic Hepatitis B and HIV Infections, run by University Hospital, Bonn at 5 sites in Germany.
Trial summary
The efficacy of pegylated interferons in the treatment of chronic hepatitis B has shown superior results to standard of care in patients only infected with hepatitis B. The efficacy of pegylated interferon for the treatment of chronic hepatitis B in HIV-coinfected patients is not known at present. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis B, HIV Infections
- What is being tested?
- pegylated interferon alfa-2a, tenofovir DF / emtricitabine combination therapy and pegIFN / TDF / FTC combination therapy
- How many people
- 2 participants
- Where
- 5 sitesGermany
- Study dates
- Sep 2004to Jan 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented chronic hepatitis B infection (> 6 months) with detectable HBV DNA > 5x100000 copies/ml (PCR-Assay) on two separate occasions
- HBe-Ag positive, anti-HBe negative
- HBs-Ag positive, anti-HBs negative
- a liver biopsy within the last 12 months prior to screening consistent with chronic hepatitis B
- Documented HIV-infection
- CD4-cell count > 200 cells/µl
Show all 11Show fewer
- Elevated serum ALT > ULN but £ 10X ULN as determined by two abnormal values taken >14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained during the screening period
- Serum-creatinine clearance > 70 ml/min, according to Cockcroft-Gault
- Anorganic phosphate > 0,65 mmol/l (2,0 mg/dl)
- Neutrophils above 1.5 G/l, Hb above 11.5 g/dl (females) or 12.5 g/dl(males), thrombocytes above 90 G/l
- Ability to understand and sign a written consent form
Who cannot join
- Older than 65 years of age, younger than 18 years of age
- Pregnancy, lactating women
- Concomitant / prior medication / hypersensitivity to study medication
- Prior use of antiretroviral therapy in particular adefovir dipivoxil, tenofovir DF, lamivudine, emtricitabine, or interferon
- Treatment with interleukin 2 or corticosteroids less than 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
- Currently receiving investigational agents unless approved by the study coordinator
Show all 34Show fewer
- History of having received any systemic anti-neoplastic (including radiation < 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
- Patients not receiving HAART (Arm A) must be expected not be in need for antiretroviral therapy for HIV-infection at any time during the study 72 weeks, as judged by the investigator.
- Hypersensitivity to any of the components of the study drugs (tenofovir, emtricitabine, pegylated interferon alfa-2a)
- Concurrent liver disease:
- Ongoing hepatitis A, C or Delta infection: positive testing for anti HAV-IgM, HCV-RNA, anti-HDV, HDV-Ag
- Ongoing EBV or CMV infection: positive testing for anti EBV-IgM, CMV-eAg
- Autoimmune hepatitis
- Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months and magnetic resonance tomography of the liver shows no evidence of hepatocellular carcinoma.
- Liver cirrhosis, CHILD-Pugh Score B or C; history or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
- History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver diseases including Wilson's and alpha1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, thalassemia).
- Alcohol abuse (> 30g ethanol/d for males, > 20 g ethanol/d for females) or use of other recreational drug substances)
- Serum total bilirubin above twice the upper limit of normal
- ALT > 10 times the upper limit of normal
- Neurological / psychiatric disorders:
- History of severe psychiatric conditions(ICD F30 - 33), graded by the consulting psychiatrist, in particular severe depression. Severe psychiatric disease is defined as major depression or psychosis, a period of treatment with an antidepressant medication or tranquilizer at therapeutic doses for depression or psychosis for at least 3 months, a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease.
- History of a severe seizure disorder or current anticonvulsant use.
- Cardiovascular disorders:
- History or other evidence of chronic pulmonary disease associated with functional limitation.
- Severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases).
- Immunological disorders:
- Elevated auto-antibody findings
- History of immunologically mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
- Thyroid disease with thyroid function poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone or T4 concentrations, with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
- Other:
- Gastrointestinal malabsorption
- Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is ³20% within 2 years. Patients with a lesion suspicious of hepatic malignancy on a screening imaging study will only be eligible if the likelihood of carcinoma is £10% following an appropriate evaluation.
- History of organ transplantation
- History or other evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
Praxiszentrum Kaiserdamm
Berlin, State of Berlin, 14057
Immunologische Ambulanz, Medizinische Klinik und Poliklinik I, Bonn University
Bonn, North-Rhine Westfalia, 53127
ifi Institut für Interdisziplinäre Medizin
Hamburg, Free and Hanseatic City of Hamburg, 20099
Praxis St. Georg
Hamburg, Free and Hanseatic City of Hamburg, 20099
Abteilung Klinische Immunologie Zentrum Innere Medizin der Medizinischen Hochschule Hannover
Hanover, Lower Saxony, 30625
About this study
Official title: Pegylated Interferon Alfa-2a Versus Emtricitabine / Tenofovir +/- Pegylated Interferon Alfa-2a for the Treatment of Chronic HBe-Ag Positive Hepatitis B Infection in HIV-Coinfected Patients - the PEGPLUS Trial
The efficacy of pegylated interferons in the treatment of chronic hepatitis B has shown superior results to standard of care in patients only infected with hepatitis B. The efficacy of pegylated interferon for the treatment of chronic hepatitis B in HIV-coinfected patients is not known at present.
The purpose of this study is to evaluate the efficacy of pegylated interferon in the treatment of chronic hepatitis B in HIV-infected individuals.
Read more
Apart from evaluating the efficacy of pegylated interferon therapy in this setting as such, i.e. in patients without present or future need of highly active antiretroviral therapy (HAART) for HIV-infection, there is a second purpose of this study, to investigate whether combination treatment of HBV-infection may be superior to pegylated interferon therapy alone.
Therefore patients without need of HAART are offered pegylated interferon alfa-2a over 48 weeks. Patients who require HAART are offered emtricitabine / tenofovir DF containing HAART over 72 weeks PLUS pegylated interferon alfa-2a over 48 weeks vs. emtricitabine / tenofovir DF containing HAART over 72 weeks WITHOUT pegylated interferon-alfa-2a.
Read the detailed description
Even though the generated data on standard interferon for the treatment of chronic HBV-infection in HIV-coinfected patients appears not promising at the moment, it is however the only treatment with a curative intention. Trials with pegylated interferon in the treatment of chronic HBV-infection in monoinfected patients with pegylated interferons showed higher efficacy than standard of care and when compared to historic data higher efficacy compared to non-pegylated interferon. This suggests in parallel a higher efficacy in the treatment of chronic hepatitis B in HIV-coinfected as well. At the same time, analysis suggested a further benefit when pegylated interferon therapy was prolonged beyond 24 weeks to 48 weeks as the elimination of HBV-DNA from serum appeared to continue beyond 24 weeks. Looking again at data from chronic hepatitis C infection, it is well known that the elimination kinetics of HCV-RNA in HIV-coinfected patients is slower compared to HCV-monoinfected patients, clearly suggesting rationale to offer 48 weeks pegylated interferon for the treatment of chronic hepatitis B to HIV-coinfected patients as well.
Parallel to the above said there are several other factors suggesting a positive effect of a combination treatment with nucleoside / nucleotide analogues active against HBV and interferon. Therefore patients in need for antiretroviral therapy with CD4-cells above 200/µl will be randomized to either PegIFN as part of a combination treatment with FTC and TDF or to FTC / TDF combination therapy alone. Patients receiving HAART will also receive a third active antiretroviral HIV-drug, either a non-nucleoside analogue (NNRTI) or a protease inhibitor (PI), at the choice of the investigator. A non-divergent antiretroviral therapy solely based on nucleoside analogues will not be allowed in this trial.
The objective of this study is to assess the efficacy (HBV-DNA < 5x10³ copies/ml, loss of HBe-Ag, HBe-seroconversion) and safety (adverse events, serious adverse events) of PegIFN for 48 weeks, to that of PegIFN for 48 weeks plus TDF and FTC containing HAART, to that of TDF and FTC containing HAART for 72 weeks.
- Conditions
- Chronic Hepatitis B, HIV Infections
- Being tested
- pegylated interferon alfa-2a, tenofovir DF / emtricitabine combination therapy, pegIFN / TDF / FTC combination therapy
- Keywords
- chronic hepatitis B, human immunodeficiency virus, pegylated interferon, tenofovir DF, emtricitabine
- Medical subject headings
- Hepatitis B, Chronic, HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pegylated interferon alfa-2aDrug
tenofovir DF / emtricitabine combination therapyDrug
pegIFN / TDF / FTC combination therapyDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: HBeAg seroconversion (HBeAg loss and presence of anti HBe) ; intent to treat analysis.
Measured: week 48 and 72
Safety: study discontinuation due to adverse events; intent to treat analysis.
Measured: week 48
Secondary outcomes (4)
Efficacy: loss of HBe-Ag,HBV-DNA < 5x10³ copies/ml(COBAS TaqMan HBV Test),decrease of HBV-DNA > 2xlog10 compared to baseline
Measured: week 48 and 72
normalization of ALT,intent to treat and as treated analysis; Viral kinetics of HBV-DNA; Paired liver biopsy comparison according to METAVIR-activity and fibrosis score.
Measured: week 48 and 72
for Arm B (B1 and B2): HIV-RNA < 50 copies/ml and CD4-cell increase intent to treat and as treated analysis
Measured: Weeks 4, 12, 24, 48 and 72
Safety: number of adverse events, according to type and severity.
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startSep 2004
- Primary completionJan 2007
- Study completionJan 2007
Why it stopped: Lack of accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bonn
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Investigators
- Jürgen K Rockstroh, MD, PhD, Study director, Bonn University, GermanyMartin - Vogel, MD, Principal investigator, Bonn University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00221286
- Sponsor's protocol ID
- ML-18150
- Status last verified
- Feb 2009
- First submitted
- 14 Sep 2005
- Last updated
- 18 Feb 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pegylated Interferon Alfa-2a Versus Emtricitabine / Tenofovir +/- Pegylated Interferon Alfa-2a for the Treatment of Chronic HBe-Ag Positive Hepatitis B Infection in HIV-Coinfected Patients - the PEGPLUS Trial
- ClinicalTrials.gov ID
- NCT00221286
- Acronym / sponsor ID
- ML-18150
- Conditions
- Chronic Hepatitis B, HIV Infections
- Keywords
- chronic hepatitis B, human immunodeficiency virus, pegylated interferon, tenofovir DF, emtricitabine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University Hospital, BonnUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- Sep 2004
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jan 2007 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The efficacy of pegylated interferons in the treatment of chronic hepatitis B has shown superior results to standard of care in patients only infected with hepatitis B. The efficacy of pegylated interferon for the treatment of chronic hepatitis B in HIV-coinfected patients is not known at present.
The purpose of this study is to evaluate the efficacy of pegylated interferon in the treatment of chronic hepatitis B in HIV-infected individuals.
Apart from evaluating the efficacy of pegylated interferon therapy in this setting as such, i.e. in patients without present or future need of highly active antiretroviral therapy (HAART) for HIV-infection, there is a second purpose of this study, to investigate whether combination treatment of HBV-infection may be superior to pegylated interferon therapy alone.
Therefore patients without need of HAART are offered pegylated interferon alfa-2a over 48 weeks. Patients who require HAART are offered emtricitabine / tenofovir DF containing HAART over 72 weeks PLUS pegylated interferon alfa-2a over 48 weeks vs. emtricitabine / tenofovir DF containing HAART over 72 weeks WITHOUT pegylated interferon-alfa-2a.
Detailed description
Even though the generated data on standard interferon for the treatment of chronic HBV-infection in HIV-coinfected patients appears not promising at the moment, it is however the only treatment with a curative intention. Trials with pegylated interferon in the treatment of chronic HBV-infection in monoinfected patients with pegylated interferons showed higher efficacy than standard of care and when compared to historic data higher efficacy compared to non-pegylated interferon. This suggests in parallel a higher efficacy in the treatment of chronic hepatitis B in HIV-coinfected as well. At the same time, analysis suggested a further benefit when pegylated interferon therapy was prolonged beyond 24 weeks to 48 weeks as the elimination of HBV-DNA from serum appeared to continue beyond 24 weeks. Looking again at data from chronic hepatitis C infection, it is well known that the elimination kinetics of HCV-RNA in HIV-coinfected patients is slower compared to HCV-monoinfected patients, clearly suggesting rationale to offer 48 weeks pegylated interferon for the treatment of chronic hepatitis B to HIV-coinfected patients as well.
Parallel to the above said there are several other factors suggesting a positive effect of a combination treatment with nucleoside / nucleotide analogues active against HBV and interferon. Therefore patients in need for antiretroviral therapy with CD4-cells above 200/µl will be randomized to either PegIFN as part of a combination treatment with FTC and TDF or to FTC / TDF combination therapy alone. Patients receiving HAART will also receive a third active antiretroviral HIV-drug, either a non-nucleoside analogue (NNRTI) or a protease inhibitor (PI), at the choice of the investigator. A non-divergent antiretroviral therapy solely based on nucleoside analogues will not be allowed in this trial.
The objective of this study is to assess the efficacy (HBV-DNA < 5x10³ copies/ml, loss of HBe-Ag, HBe-seroconversion) and safety (adverse events, serious adverse events) of PegIFN for 48 weeks, to that of PegIFN for 48 weeks plus TDF and FTC containing HAART, to that of TDF and FTC containing HAART for 72 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Documented chronic hepatitis B infection (> 6 months) with detectable HBV DNA > 5x100000 copies/ml (PCR-Assay) on two separate occasions
- HBe-Ag positive, anti-HBe negative
- HBs-Ag positive, anti-HBs negative
- a liver biopsy within the last 12 months prior to screening consistent with chronic hepatitis B
- Documented HIV-infection
Key exclusion criteria (34 listed)
- Older than 65 years of age, younger than 18 years of age
- Pregnancy, lactating women
- Concomitant / prior medication / hypersensitivity to study medication
- Prior use of antiretroviral therapy in particular adefovir dipivoxil, tenofovir DF, lamivudine, emtricitabine, or interferon
- Treatment with interleukin 2 or corticosteroids less than 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pegylated interferon alfa-2a | Drug | – |
| tenofovir DF / emtricitabine combination therapy | Drug | – |
| pegIFN / TDF / FTC combination therapy | Drug | – |
Primary outcome
Efficacy: HBeAg seroconversion (HBeAg loss and presence of anti HBe) ; intent to treat analysis.
Time frame: week 48 and 72
Safety: study discontinuation due to adverse events; intent to treat analysis.
Time frame: week 48
4 secondary outcomes
Efficacy: loss of HBe-Ag,HBV-DNA < 5x10³ copies/ml(COBAS TaqMan HBV Test),decrease of HBV-DNA > 2xlog10 compared to baseline
Time frame: week 48 and 72
normalization of ALT,intent to treat and as treated analysis; Viral kinetics of HBV-DNA; Paired liver biopsy comparison according to METAVIR-activity and fibrosis score.
Time frame: week 48 and 72
for Arm B (B1 and B2): HIV-RNA < 50 copies/ml and CD4-cell increase intent to treat and as treated analysis
Time frame: Weeks 4, 12, 24, 48 and 72
Safety: number of adverse events, according to type and severity.
Time frame: Throughout study
Results and safety
The study was stopped early (reason given: Lack of accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jürgen K Rockstroh, MD, PhD study director
Bonn University, Germany
Martin - Vogel, MD principal investigator
Bonn University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing pegylated interferon alfa-2a, tenofovir DF / emtricitabine combination therapy and pegIFN / TDF / FTC combination therapy in people with Chronic Hepatitis B and HIV Infections, run by University Hospital, Bonn at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy: HBeAg seroconversion (HBeAg loss and presence of anti HBe) ; intent to treat analysis. (time frame: week 48 and 72). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2009.