Carcinoma, HepatocellularPhase 3NCT00759109
Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085)
A Phase 3 study testing Peginterferon alfa-2b and Observation (no treatment) in people with Carcinoma, Hepatocellular, run by Merck Sharp & Dohme LLC.
Trial summary
This study aims to compare the role of peginterferon α-2b (50 μg/week) vs. control (no treatment) in the prevention of hepatocellular carcinoma, in adult patients with cirrhosis and initial signs of portal hypertension who did not respond to previous combined therapy with interferon alfa + ribavirin or peginterferon… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Peginterferon alfa-2b and Observation (no treatment)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- Mar 2002to Nov 2009
- Phase
- Phase 3
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cirrhotic participants, both sexes, Child Pugh A, B, HCV-RNA positive, age < 70 years
- Participants non-responders to IFN + Ribavirin or PegIFN + Ribavirin or IFN monotherapy
- Pre-therapy liver biopsy (< 36 months) with PCNA-LI > 2.0
- Fibrosis score 5-6 (Ishak)
- Initial portal hypertension, such as gastroesophageal varices or one of the following US sign:
- Collateral circles
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- Spleen longitudinal diameter > 12 cm
- Portal vein diameter at hilus > 12 mm
- Portal flow > 12 cm/sec
- Participants must have the following minimum hematologic and biochemical criteria:
- Hemoglobin >= 11 g/dL
- Granulocyte count > 1,000/mm^3
- Platelets > 70,000/mm^3
- Prothrombin activity > 50%
- Total bilirubin <3 mg/dL
- Albumin >= 3.5 g/dL
- Serum creatinine within normal limits
- Uric Acid within normal limits
- Thyroid Stimulating Hormone (TSH), within normal limits
- Antinuclear antibodies (ANA) < 1:160
- Written informed consent
- Women of childbearing potential must have a negative pregnancy test
- Acceptance of patients of both sexes of proper contraceptive measures for the study period
Who cannot join
- Pregnant or breast-feeding women
- Co-infection with HIV and/or HBV
- Autoimmune hepatitis or history of autoimmune disease
- Alcoholic liver disease
- Metabolic disease
- HCC
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- Participants with liver and kidney transplants
- Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy
- Chronic renal failure or creatinine clearance < 50 mL/min
- Pre-existing thyroid disease unless it can be controlled with conventional treatment
- History or presence of psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt
- Epilepsy and/or compromised central nervous system (CNS) function
- Significant cardiovascular dysfunction within the previous 6 months before the study starts (eg, angina, congestive heart failure, recent myocardial infarction, moderate or severe hypertension, significant arrhythmia)
- Hemoglobinopathies
- Poorly controlled diabetes mellitus
- Chronic pulmonary disease (eg, chronic obstructive pulmonary disease)
- Clinical gout
- Hypersensitivity to interferons or any component of the drug
About this study
Official title: Long-term Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation: a Multicenter Study of Hepatocellular Carcinoma Prevention in Patients Non-responders to Combined Therapy With Alpha Interferon + Ribavirin or Peginterferon Alpha + Ribavirin or to Interferon Monotherapy
This study aims to compare the role of peginterferon α-2b (50 μg/week) vs. control (no treatment) in the prevention of hepatocellular carcinoma, in adult patients with cirrhosis and initial signs of portal hypertension who did not respond to previous combined therapy with interferon alfa + ribavirin or peginterferon alfa + ribavirin or to interferon alfa monotherapy and with a high proliferation rate before entering the study. The duration of treatment will be 3 years, and the follow-up period will be 2 years.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Peginterferon alfa-2b, Observation (no treatment)
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peginterferon alfa-2bBiological
Also called PegIntron, Pegylated Alfa-2b, SCH 054031
Peginterferon alfa-2b, 50 μg, weekly, SC, for a period of 3 years.
Observation (no treatment)Other
No treatment was given to participants enrolled in the control arm (Arm B).
| Study group | Role | What they receive |
|---|---|---|
| Arm A - PegIntron | Experimental | Participants randomized to Arm A received peginterferon α-2b (PegIntron), 50 μg, weekly, subcutaneously (SC), for a period of 3 years. Receives: Biological: Peginterferon alfa-2b |
| Arm B - Control | Other | Participants randomized to Arm B were under observation and received no treatment. Receives: Other: Observation (no treatment) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With the Development of Hepatocellular Carcinoma (HCC)
Participants were tested for focal lesions by liver ultrasound and for AFP levels every 6 months the during study (treatment and follow-up).
The development of hepatocellular carcinoma was determined by:
- the appearance of a focal lesion detected by liver ultrasound with metastases confirmed by fine needle biopsy, or
- the appearance of a focal lesion detected by ultrasound + alphafetoprotein (AFP) levels in blood >400 ng/mL.
Measured: During 3 years of treatment and 2 years of follow-up
Secondary outcomes (4)
Number of Participants With Development of Hepatic Decompensation
The development of hepatic decompensation, defined as worsening of the hepatic function as measured by Child Pugh Score. The Child Pugh score was calculated based on biochemical changes (changes in serum albumin, serum bilirubin, prothrombin time) and clinical impairment (ascites, encephalopathies) or both. Each of the 5 parameters was scored from 1-3, and the Child Pugh Score represented the total score. The maximum score was 15, and a score of 10-15 represents the worst outcome and a life expectancy of 1-3 years.
Measured: Baseline, During 3 years of treatment and 2 years of follow-up
Survival Time of Participants
Survival time was defined as time from screening visit to the death of the participant and was studied with Kaplan-Meier and Log-rank tests. If a participant did not die, he or she was censored with the last available date.
Measured: During 3 years of treatment and 2 years of follow-up
Number of Patients With a Virological Response Rate
Virological Response rate was measured by the disappearance of Hepatitis C Virus from serum. Serum samples from participants were analyzed for the
presence of HCV-RNA using a qualitative polymerase chain reaction (PCR).
Measured: Baseline and every year during 3 years of treatment
Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)
PCNA-LI was measured at baseline and at 18 months of treatment, and the change in PCNA-LI was calculated.
To measure PCNA-LI, liver tissue samples obtained from biopsies were fixed and immunostained to detect PCNA. PCNA-LI is the percentage of immunohistochemically stained (PCNA positive) cells in 1,000 HCC cells counted. A higher PCNA-LI indicates a worse outcome.
Measured: Baseline and at 18 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2008 (estimated)
- Study startMar 2002
- Primary completionNov 2009
- Study completionNov 2009
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.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00759109
- Sponsor's protocol ID
- P02733
- Status last verified
- Mar 2017
- First submitted
- 26 Aug 2008
- Last updated
- 7 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation: a Multicenter Study of Hepatocellular Carcinoma Prevention in Patients Non-responders to Combined Therapy With Alpha Interferon + Ribavirin or Peginterferon Alpha + Ribavirin or to Interferon Monotherapy
- ClinicalTrials.gov ID
- NCT00759109
- Acronym / sponsor ID
- P02733
- Conditions
- Carcinoma, Hepatocellular
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Mar 2002
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 25 Sep 2008 (estimated)
- Results
- Posted 18 Apr 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 aims to compare the role of peginterferon α-2b (50 μg/week) vs. control (no treatment) in the prevention of hepatocellular carcinoma, in adult patients with cirrhosis and initial signs of portal hypertension who did not respond to previous combined therapy with interferon alfa + ribavirin or peginterferon alfa + ribavirin or to interferon alfa monotherapy and with a high proliferation rate before entering the study. The duration of treatment will be 3 years, and the follow-up period will be 2 years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - PegIntron | Experimental | Biological: Peginterferon alfa-2bParticipants randomized to Arm A received peginterferon α-2b (PegIntron), 50 μg, weekly, subcutaneously (SC), for a period of 3 years. |
| Arm B - Control | Other | Other: Observation (no treatment)Participants randomized to Arm B were under observation and received no treatment. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Cirrhotic participants, both sexes, Child Pugh A, B, HCV-RNA positive, age < 70 years
- Participants non-responders to IFN + Ribavirin or PegIFN + Ribavirin or IFN monotherapy
- Pre-therapy liver biopsy (< 36 months) with PCNA-LI > 2.0
- Fibrosis score 5-6 (Ishak)
- Initial portal hypertension, such as gastroesophageal varices or one of the following US sign:
Key exclusion criteria (18 listed)
- Pregnant or breast-feeding women
- Co-infection with HIV and/or HBV
- Autoimmune hepatitis or history of autoimmune disease
- Alcoholic liver disease
- Metabolic disease
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-2bAlso: PegIntron, Pegylated Alfa-2b, SCH 054031Peginterferon alfa-2b, 50 μg, weekly, SC, for a period of 3 years. | Biological | Arm A - PegIntron |
| Observation (no treatment)No treatment was given to participants enrolled in the control arm (Arm B). | Other | Arm B - Control |
Primary outcome
Number of Participants With the Development of Hepatocellular Carcinoma (HCC)
Time frame: During 3 years of treatment and 2 years of follow-up
Participants were tested for focal lesions by liver ultrasound and for AFP levels every 6 months the during study (treatment and follow-up). The development of hepatocellular carcinoma was determined by: 1. the appearance of a focal lesion detected by liver ultrasound with metastases confirmed by fine needle biopsy, or 2. the appearance of a focal lesion detected by ultrasound + alphafetoprotein (AFP) levels in blood >400 ng/mL.
4 secondary outcomes
Number of Participants With Development of Hepatic Decompensation
Time frame: Baseline, During 3 years of treatment and 2 years of follow-up
Survival Time of Participants
Time frame: During 3 years of treatment and 2 years of follow-up
Number of Patients With a Virological Response Rate
Time frame: Baseline and every year during 3 years of treatment
Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)
Time frame: Baseline and at 18 months of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Peginterferon alfa-2b and Observation (no treatment) in people with Carcinoma, Hepatocellular, run by Merck Sharp & Dohme LLC.
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 23 inclusion and 18 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 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 18 Apr 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?
Number of Participants With the Development of Hepatocellular Carcinoma (HCC) (time frame: During 3 years of treatment and 2 years of follow-up). 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 7 Apr 2017.