Hepatitis CPhase 4NCT00056862
Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected With HCV Genotype 2 or 3
A Phase 4 study testing Peginterferon alfa-2a and Ribavirin in people with Hepatitis C, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
This study will examine the effectiveness of low-dose peginterferon and ribavirin therapy for certain patients with chronic hepatitis C-a liver disease that, in some patients, can progress to cirrhosis of the liver, liver cancer, and liver failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Peginterferon alfa-2a and Ribavirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2003to Jun 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age above 18 years, male or female.
- Presence of anti-HCV in serum.
- Positive HCV RNA determination in serum.
- HCV genotype 2 or 3 as determined by Inno LiPa assay or by direct sequencing. Patients with mixed genotypes will not be eligible if they have genotypes other than 2 or 3.
- Written informed consent.
Who cannot join
- Previous treatment with interferon alpha or peginterferon.
- Decompensated liver disease, as marked by bilirubin greater than 4 mg/dL, albumin less than 3.0 g/dL, prothrombin time greater than 2 sec prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy.
- Patients with ALT levels greater than 1000 U/L (greater than 25 times ULN) will not be enrolled but may be followed until three determinations are below this level.
- Pregnancy or, in women of child-bearing potential or in spouses of such women, inability to practice adequate contraception, defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicidal, or birth control pills, or an intrauterine device.
- Significant systemic or major illnesses other than liver disease, including congestive heart failure, renal failure (creatinine clearance less than 50 ml/min), organ transplantation, serious psychiatric disease not controlled by psychotropic agents, and angina pectoris.
- Evidence of coronary artery disease or cerebral vascular disease, including abnormalities on exercise stress testing in patients with defined risk factors who will be screened for evidence of underlying coronary artery disease.
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- Pre-existing, severe bone marrow compromise; anemia (hematocrit less than 30%), neutropenia (less than 1000 neutrophils/microliter) or thrombocytopenia (less than 70,000 cells/microliter).
- History of hemolytic anemia.
- Evidence of another form of liver disease in addition to hepatitis C (for example hepatitis B, autoimmune liver disease, Wilson's disease, alcoholic liver disease).
- Active substance abuse, such as alcohol, inhaled or injection drugs within the previous six months.
- Evidence of hepatocellular carcinoma: either alfa-fetoprotein (AFP) levels greater than 50 ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study) demonstrating a mass suggestive of liver cancer.
- Clinical gout.
- HIV infection.
- Quiescent or active, serious autoimmune disease such as lupus erythematosus, ulcerative colitis, Crohn's disease or rheumatoid arthritis that in the opinion of the investigators might be exacerbated by therapy with alfa interferon.
- The use of immunosuppressive medications, including corticosteroids in doses of 10 mg of prednisone or its equivalent and higher.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Low Dose Peginterferon and Ribavirin Therapy for Patients With Chronic Hepatitis C Infected With Genotype 2 or 3
This study will examine the effectiveness of low-dose peginterferon and ribavirin therapy for certain patients with chronic hepatitis C-a liver disease that, in some patients, can progress to cirrhosis of the liver, liver cancer, and liver failure.
Read the detailed description
Sixty patients with chronic hepatitis C infected with HCV genotype 2 or 3 will be treated using the combination of either low- or standard dose peginterferon and ribavirin for 24 weeks, with re-treatment using the standard doses and a longer duration (48 weeks) for those who do not respond to or relapse after initial low dose therapy.
Adult patients with chronic hepatitis C who have HCV genotype 2 or 3 and previously have not received anti-viral treatment will be given peginterferon alfa-2a (90 or 180 micrograms weekly by injection) and ribavirin (800 mg daily by mouth). Patients will be monitored at 2- to 4-week intervals for side effects, compliance, complete blood counts, liver biochemical tests and HCV RNA. Patients becoming HCV RNA negative by week 12 will be considered on-treatment responders, continue therapy to week 24, and be monitored thereafter for another 24 weeks. Patients who do not become HCV RNA negative by week 12 as well as patients who relapse after therapy will be retreated with 180 micrograms of peginterferon weekly and 800 mg of ribavirin for another 48 weeks.
The primary outcome will be sustained loss of HCV RNA at 24 weeks after low- or standard-dose combination therapy. Secondary outcomes include viral kinetics and side effects. Because of preliminary results in the initial 31 patients enrolled in this study, the dose of peginterferon was changed from 90 to 180 micrograms weekly for the remaining 29 patients to be enrolled, allowing for a direct comparison of efficacy, viral kinetics and side effects of standard- vs low-dose peginterferon therapy.
This study will evaluate the relative efficacy and safety of the standard versus lower doses of peginterferon with ribavirin in patients with chronic hepatitis C and HCV genotype 2 or 3.
- Conditions
- Hepatitis C
- Being tested
- Peginterferon alfa-2a, Ribavirin
- Keywords
- Hepatitis C Virus, Antiviral Agents, Hemolysis, Neutropenia, Cirrhosis, Hemolytic Anemia, Viral Hepatitis, Ribavirin, Alfa Interferon, Pegylated Interferon, Hepatitis C, HCV
- Medical subject headings
- Hepatitis C, Hemolysis, Neutropenia, Fibrosis, Anemia, Hemolytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peginterferon alfa-2aDrug
Also called Pegasys
Peginterferon alfa-2a 90 mcg/week
Peginterferon alfa-2aDrug
Also called Pegasys
180 mcg/week
RibavirinDrug
Also called Copegus
800 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Low-dose pegIFN/standard-dose RBV | Experimental | Patients receive a lower dose of peginterferon alfa-2a (90 mcg per week) and standard dose of ribavirin (800 mg/d) for chronic hepatitis C, genotype 2/3, for 24 weeks. Receives: Drug: Peginterferon alfa-2a; Drug: Ribavirin |
| Standard-dose PegIFN/RBV | Active comparator | Patients receive the standard, recommended doses of peginterferon alfa-2a (180 mcg per week) and ribavirin (800 mg/d) for chronic hepatitis c, genotype 2/3, for 24 weeks. Receives: Drug: Peginterferon alfa-2a; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virological Response (Intention to Treat)
Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
Measured: 6 months after stopping therapy
Virological Response Category (Per Protocol)
Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
Measured: 6 months after therapy
Secondary outcomes (3)
First Phase Decline in Logarithm of HCV RNA Level
The 1st phase decline is defined as the log difference between baseline HCV RNA level and the level on day 2 of treatment (see Neumann et al, Science, 1998).
Measured: 2 days
Slope of Second Phase Decline in HCV Levels
The 2nd phase slope is defined as the slope of the logarithmic viral levels from week 1 to week 4 of treatment (see Neumann et al, Science, 1998).
Measured: day 7 to day 28
Time to Negativity
Time from treatment initiation to the first negative HCV RNA test during treatment
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2003 (estimated)
- Study startMar 2003
- Primary completionJan 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rotman Yaron, MD, Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00056862
- Sponsor's protocol ID
- 030136
- Other IDs
- 03-DK-0136
- Status last verified
- Nov 2013
- First submitted
- 25 Mar 2003
- Last updated
- 6 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000 Feb 15;132(4):296-305. doi: 10.7326/0003-4819-132-4-200002150-00008.
PubMed 10681285Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. doi: 10.1056/NEJM200107053450107. No abstract available.
PubMed 11439948Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998 Oct 2;282(5386):103-7. doi: 10.1126/science.282.5386.103.
PubMed 9756471Rotman Y, Borg BB, Soza A, Feld JJ, Modi AA, Loomba R, Lutchman G, Rivera E, Doo E, Ghany MG, Heller T, Neumann AU, Liang TJ, Hoofnagle JH. Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response. Aliment Pharmacol Ther. 2010 May;31(9):1018-27. doi: 10.1111/j.1365-2036.2010.04263.x. Epub 2010 Jan 16.
PubMed 20163377
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose Peginterferon and Ribavirin Therapy for Patients With Chronic Hepatitis C Infected With Genotype 2 or 3
- ClinicalTrials.gov ID
- NCT00056862
- Acronym / sponsor ID
- 030136
- Conditions
- Hepatitis C
- Keywords
- Hepatitis C Virus, Antiviral Agents, Hemolysis, Neutropenia, Cirrhosis, Hemolytic Anemia, Viral Hepatitis, Ribavirin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- Mar 2003
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 25 Mar 2003 (estimated)
- Results
- Posted 27 Jun 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the effectiveness of low-dose peginterferon and ribavirin therapy for certain patients with chronic hepatitis C-a liver disease that, in some patients, can progress to cirrhosis of the liver, liver cancer, and liver failure.
Detailed description
Sixty patients with chronic hepatitis C infected with HCV genotype 2 or 3 will be treated using the combination of either low- or standard dose peginterferon and ribavirin for 24 weeks, with re-treatment using the standard doses and a longer duration (48 weeks) for those who do not respond to or relapse after initial low dose therapy.
Adult patients with chronic hepatitis C who have HCV genotype 2 or 3 and previously have not received anti-viral treatment will be given peginterferon alfa-2a (90 or 180 micrograms weekly by injection) and ribavirin (800 mg daily by mouth). Patients will be monitored at 2- to 4-week intervals for side effects, compliance, complete blood counts, liver biochemical tests and HCV RNA. Patients becoming HCV RNA negative by week 12 will be considered on-treatment responders, continue therapy to week 24, and be monitored thereafter for another 24 weeks. Patients who do not become HCV RNA negative by week 12 as well as patients who relapse after therapy will be retreated with 180 micrograms of peginterferon weekly and 800 mg of ribavirin for another 48 weeks.
The primary outcome will be sustained loss of HCV RNA at 24 weeks after low- or standard-dose combination therapy. Secondary outcomes include viral kinetics and side effects. Because of preliminary results in the initial 31 patients enrolled in this study, the dose of peginterferon was changed from 90 to 180 micrograms weekly for the remaining 29 patients to be enrolled, allowing for a direct comparison of efficacy, viral kinetics and side effects of standard- vs low-dose peginterferon therapy.
This study will evaluate the relative efficacy and safety of the standard versus lower doses of peginterferon with ribavirin in patients with chronic hepatitis C and HCV genotype 2 or 3.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-dose pegIFN/standard-dose RBV | Experimental | Drug: Peginterferon alfa-2a, Drug: RibavirinPatients receive a lower dose of peginterferon alfa-2a (90 mcg per week) and standard dose of ribavirin (800 mg/d) for chronic hepatitis C, genotype 2/3, for 24 weeks. |
| Standard-dose PegIFN/RBV | Active comparator | Drug: Peginterferon alfa-2a, Drug: RibavirinPatients receive the standard, recommended doses of peginterferon alfa-2a (180 mcg per week) and ribavirin (800 mg/d) for chronic hepatitis c, genotype 2/3, for 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age above 18 years, male or female.
- Presence of anti-HCV in serum.
- Positive HCV RNA determination in serum.
- HCV genotype 2 or 3 as determined by Inno LiPa assay or by direct sequencing. Patients with mixed genotypes will not be eligible if they have genotypes other than 2 or 3.
- Written informed consent.
Key exclusion criteria (15 listed)
- Previous treatment with interferon alpha or peginterferon.
- Decompensated liver disease, as marked by bilirubin greater than 4 mg/dL, albumin less than 3.0 g/dL, prothrombin time greater than 2 sec prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy.
- Patients with ALT levels greater than 1000 U/L (greater than 25 times ULN) will not be enrolled but may be followed until three determinations are below this level.
- Pregnancy or, in women of child-bearing potential or in spouses of such women, inability to practice adequate contraception, defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicidal, or birth control pills, or an intrauterine device.
- Significant systemic or major illnesses other than liver disease, including congestive heart failure, renal failure (creatinine clearance less than 50 ml/min), organ transplantation, serious psychiatric disease not controlled by psychotropic agents, and angina pectoris.
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 |
|---|---|---|
| Peginterferon alfa-2aAlso: PegasysPeginterferon alfa-2a 90 mcg/week | Drug | Low-dose pegIFN/standard-dose RBV |
| Peginterferon alfa-2aAlso: Pegasys180 mcg/week | Drug | Standard-dose PegIFN/RBV |
| RibavirinAlso: Copegus800 mg/day | Drug | Low-dose pegIFN/standard-dose RBV, Standard-dose PegIFN/RBV |
Primary outcome
Virological Response (Intention to Treat)
Time frame: 6 months after stopping therapy
Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
Virological Response Category (Per Protocol)
Time frame: 6 months after therapy
Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
3 secondary outcomes
First Phase Decline in Logarithm of HCV RNA Level
Time frame: 2 days
Slope of Second Phase Decline in HCV Levels
Time frame: day 7 to day 28
Time to Negativity
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10681285Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000 Feb 15;132(4):296-305. doi: 10.7326/0003-4819-132-4-200002150-00008.
- Background: PubMed 11439948Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. doi: 10.1056/NEJM200107053450107. No abstract available.
- Background: PubMed 9756471Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998 Oct 2;282(5386):103-7. doi: 10.1126/science.282.5386.103.
- Results publication: PubMed 20163377Rotman Y, Borg BB, Soza A, Feld JJ, Modi AA, Loomba R, Lutchman G, Rivera E, Doo E, Ghany MG, Heller T, Neumann AU, Liang TJ, Hoofnagle JH. Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response. Aliment Pharmacol Ther. 2010 May;31(9):1018-27. doi: 10.1111/j.1365-2036.2010.04263.x. Epub 2010 Jan 16.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Rotman Yaron, MD principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Peginterferon alfa-2a and Ribavirin in people with Hepatitis C, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
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 5 inclusion and 15 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: finished, as of the sponsor's last update on 6 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Virological Response (Intention to Treat) (time frame: 6 months after stopping therapy). 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?
On the ClinicalTrials.gov record for NCT00056862, which also lists 4 linked publications.
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 6 Dec 2013.