Hepatitis C, ChronicPhase 3NCT00441584
The Effects of PegIntron Plus Rebetol in Subjects With Chronic Hepatitis C Not Responding to Pegasys (Study P03833)
A Phase 3 study testing PegIntron (peginterferon alfa-2b) and Rebetol (ribavirin) in people with Hepatitis C, Chronic, run by Merck Sharp & Dohme LLC.
Trial summary
This is an uncontrolled, non-randomized, open-label, multinational study designed to evaluate the efficacy and safety of PegIntron plus Rebetol in subjects with chronic hepatitis C. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- PegIntron (peginterferon alfa-2b) and Rebetol (ribavirin)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- No sites listed yet
- Study dates
- Jul 2005to Jun 2008
- 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
- Subject must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
- Subject must be 18-70 years of age of either sex and of any race.
- Subject must be diagnosed with chronic hepatitis C genotype 1 (confirmation by biopsy not required). (Liver function tests (LFTs) can be normal or elevated.)
- Female subjects cannot be pregnant or breastfeeding and must be either postmenopausal, surgically sterile or using 2 methods of birth control. While abstinence from sexual activity is the only certain method to prevent pregnancy, female patients of childbearing potential who are or who anticipate the possibility of becoming sexually active with a male partner must use a combination of the following 2 methods:
- Contraceptive pill or intrauterine device (IUD) or depot hormonal preparation (ring, injection, implant), and
- A barrier method of contraception such as diaphragm, sponge with spermicide, condom, or a method of birth control considered acceptable by the study physician.
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- Contraceptive measures will be reviewed with female subjects at each visit. Dual methods of contraception must be used for 6 months after treatment discontinuation.
- Female subjects of childbearing potential must have a negative serum pregnancy test at screen phase and during the study.
- Confirmation by the principal investigator or a sub-investigator that sexually active male subjects are practicing a method of contraception considered acceptable (vasectomy, condom plus spermicide, plus relationship with a female partner who practices an acceptable method of contraception). Contraception must be used during the treatment period and for seven months after the completion of therapy, including condom use by male subjects with pregnant partners.
- Subject must be free of any clinically significant disease that would interfere with study evaluations.
- Subject must understand, be able to and agree to adhere to the dosing and visit schedules.
- Compensated liver disease with the following minimum hematologic and biochemical criteria at the Day 1 visit within normal limits:
- Hemoglobin values equal to or greater than 12 g/dL for females and 13 g/dL for males
- White blood cell (WBC) count equal to or greater than 3,000/cu mm
- Neutrophil count equal to or greater than 1,500/cu mm
- Platelet count equal to or greater than 80,000/cu mm
- Direct bilirubin within normal limits
- Indirect bilirubin within normal limits (unless non-hepatitis related factors such as Gilbert's disease explain an indirect bilirubin rise). In such cases indirect bilirubin should be less than or equal to 3.0 mg/dL (less than or equal to 51.3 µmol/L)
- Albumin within normal limits
- Serum creatinine within normal limits
- Subject must be a non-responder, defined as having received and not having responded to a prior treatment consisting of one course of Pegasys 180 mcg QW in combination with ribavirin 1000-1200 mg daily, with or without amantadine, for a minimum of 12 weeks and:
- Subject must be found to be hepatitis C virus (HCV)-ribonucleic acid (RNA) positive with less than a 2-log drop at 12 weeks of treatment, or
- is polymerase chain reaction (PCR)-positive at End Of Treatment, whether End Of Treatment happened at week 48 or earlier
- Subject must be off Pegasys/ribavirin at least 12 weeks prior to screen.
- Subject must have had no other treatment with any interferon except Pegasys.
- Subject must neither have received nor currently be on any other treatment for his chronic hepatitis C disease, except for amantadine.
- When available, historical liver biopsy with pathology report of the subject must confirm that the histological diagnosis is consistent with chronic hepatitis C.
- Subject must have a value of thyroid stimulating hormone within normal limits (whether euthyroid or requiring thyroid medications).
- Antinuclear antibodies must be less than or equal to 1:320.
- If abdominal imaging has been performed within 1 year prior to screen, it must not show evidence of focal mass suggestive of hepatoma and/or ascites.
- For subjects with a history of diabetes or hypertension, clearance from an ophthalmologist has to be obtained prior to treatment start.
Who cannot join
- Subject is a female who is pregnant or breastfeeding, or who intends to become pregnant during the study.
- Subject has used any investigational product within 30 days prior to enrollment or is currently involved in another clinical trial.
- Subjects weighing over 125 kg.
- Subject has any of the following causes for the liver disease based on subject history or biopsy (where applicable) other than chronic hepatitis C, including but not limited to:
- Hemochromatosis
- Alpha-1 antitrypsin deficiency
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- Wilson's disease
- Autoimmune hepatitis
- Alcoholic liver disease
- Non-alcoholic steatohepatitis (NASH)
- Drug-related liver disease
- Subject has any clinically significant deviation from normal in the physical examination, chest x-ray, or electrocardiogram (ECG) that, in the investigator's judgment, may interfere with the study evaluation or affect subject safety.
- Subject is in a situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
- Subject is part of the staff or a family member of the staff personnel directly involved with this study.
- Subject is a previously untreated subject.
- Subject has been treated with Pegasys + less than 1000 mg of ribavirin (instead of with 1000-1200 mg of ribavirin).
- Subject has been discontinued from Pegasys treatment at any week due to an adverse event.
- Subject is co-infected with human immunodeficiency virus (HIV) and/or hepatitis B virus (HBV).
- Subject is suspected to be hypersensitive to interferon alpha or Peg-Intron or ribavirin.
- Subject has previously received interferon, (except for the Pegasys flat dose 180 mcg QW for at least 12 weeks), thymosin or Cell Cept treatment or any other drug intended to treat chronic hepatitis C.
- Subject has had organ transplants other than cornea and hair transplant.
- Subject has a history of hepatocellular carcinoma or any other malignancy (except basal cell carcinoma) within the last 5 years or a suspected diagnosis of hepatocellular carcinoma or other malignancy, or an active malignancy.
- Known coagulation diseases such as hemophilia; hemoglobin diseases (e.g. thalassemia).
- Subject has glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Subject has an evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy.
- Subject has any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study as followed below:
- Preexisting psychiatric condition, especially moderate to severe depression, or a history of severe psychiatric disorder, such as psychosis, suicidal ideation, or suicide attempts. Severe depression includes the following:
- Hospitalization for depression
- Electroconvulsive therapy for depression, or
- Depression causing a prolonged absence from work or significantly altering daily functions.
- Subjects with mild depression may be considered for entry into the study provided that a pre-treatment assessment demonstrates that the subject's emotional status is clinically stable, in which case a management plan must be formulated for the subject; this management plan will become a part of the subject's medical record.
- Craniocerebral trauma, which is not a concussion, or active seizure disorders requiring medication.
- Clinically significant ECG abnormalities and/or cardiovascular dysfunction within 6 previous months (e.g., angina, congestive heart failure, recent myocardial infarction, or significant arrhythmia).
- Chronic lung disease (e.g., chronic obstructive lung disease)
- Poorly controlled diabetes mellitus: HbA1C more than or equal to 8.5%
- Immune-mediated disease (e.g., inflammatory bowel disease [Crohn's disease, ulcerative colitis], idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis)
- Clinical gout
- Creatinine clearance less than or equal to 50 mL/min
- any medical condition which may require use of chronic systemic steroids
- Subject is or was a substance abuser, such as alcohol (80 g/day or more), methadone, intravenous (IV), oral or inhaled drugs. To be considered for inclusion, the subject must have abstained and agree to abstain from using any of the above for at least 6 months. Subjects treated with buprenorphine (Subutex) who have been stable for 6 months may be included.
About this study
Official title: Efficacy and Safety of PEG-Intron Plus Rebetol in Subjects With Chronic Hepatitis C Genotype 1 Non Responder to Pegasys
This is an uncontrolled, non-randomized, open-label, multinational study designed to evaluate the efficacy and safety of PegIntron plus Rebetol in subjects with chronic hepatitis C. The study is designed to determine the proportion of chronic hepatitis C genotype 1 subjects who did not respond to previous treatment with Pegasys 180µg QW plus ribavirin, that will achieve sustained virological response (SVR) when treated with PegIntron plus Rebetol.
- Conditions
- Hepatitis C, Chronic
- Being tested
- PegIntron (peginterferon alfa-2b), Rebetol (ribavirin)
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegIntron (peginterferon alfa-2b)Biological
Also called SCH 54031, PEG-Intron, PegIntron, ViraferonPeg, peginterferon alfa-2b
Powder for injection in vial or Redipen (50, 80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 48 weeks
Rebetol (ribavirin)Drug
Also called SCH 18908, Rebetol, REBETOL, ribavirin
200 mg capsules, oral, weight based dose of 800-1400 mg, daily for up to 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| PegIntron plus Rebetol | Experimental | PegIntron 1.5 μg/kg/week plus Rebetol 800-1400 mg/day administered for 48 weeks Receives: Biological: PegIntron (peginterferon alfa-2b); Drug: Rebetol (ribavirin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Who Have Achieved Sustained Virological Response (SVR) at 24 Weeks Post End of Treatment
Sustained virologic response is defined as a plasma HCV RNA level below Lower Level of Quantitation at 24 weeks post-treatment, which is < 30 IU/mL in this study.
Measured: Up to 48 weeks of treatment plus 24 weeks follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2007 (estimated)
- Study startJul 2005
- Primary completionJun 2008
- Study completionJun 2008
Why it stopped: Subject accrual was prematurely terminated due slow enrollment.
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 Hepatitis C, ChronicStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Integrated Therapeutics Group
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441584
- Sponsor's protocol ID
- P03833
- Other IDs
- ESPECIAL
- Status last verified
- Mar 2017
- First submitted
- 28 Feb 2007
- Last updated
- 5 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 5 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of PEG-Intron Plus Rebetol in Subjects With Chronic Hepatitis C Genotype 1 Non Responder to Pegasys
- ClinicalTrials.gov ID
- NCT00441584
- Acronym / sponsor ID
- P03833
- Conditions
- Hepatitis C, Chronic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Subject accrual was prematurely terminated due slow enrollment.
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- Integrated Therapeutics Group
- Study start
- Jul 2005
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 1 Mar 2007 (estimated)
- Results
- Posted 4 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an uncontrolled, non-randomized, open-label, multinational study designed to evaluate the efficacy and safety of PegIntron plus Rebetol in subjects with chronic hepatitis C. The study is designed to determine the proportion of chronic hepatitis C genotype 1 subjects who did not respond to previous treatment with Pegasys 180µg QW plus ribavirin, that will achieve sustained virological response (SVR) when treated with PegIntron plus Rebetol.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PegIntron plus Rebetol | Experimental | Biological: PegIntron (peginterferon alfa-2b), Drug: Rebetol (ribavirin)PegIntron 1.5 μg/kg/week plus Rebetol 800-1400 mg/day administered for 48 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Subject must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
- Subject must be 18-70 years of age of either sex and of any race.
- Subject must be diagnosed with chronic hepatitis C genotype 1 (confirmation by biopsy not required). (Liver function tests (LFTs) can be normal or elevated.)
- Female subjects cannot be pregnant or breastfeeding and must be either postmenopausal, surgically sterile or using 2 methods of birth control. While abstinence from sexual activity is the only certain method to prevent pregnancy, female patients of childbearing potential who are or who anticipate the possibility of becoming sexually active with a male partner must use a combination of the following 2 methods:
- Contraceptive measures will be reviewed with female subjects at each visit. Dual methods of contraception must be used for 6 months after treatment discontinuation.
Key exclusion criteria (40 listed)
- Subject is a female who is pregnant or breastfeeding, or who intends to become pregnant during the study.
- Subject has used any investigational product within 30 days prior to enrollment or is currently involved in another clinical trial.
- Subjects weighing over 125 kg.
- Subject has any of the following causes for the liver disease based on subject history or biopsy (where applicable) other than chronic hepatitis C, including but not limited to:
- Subject has any clinically significant deviation from normal in the physical examination, chest x-ray, or electrocardiogram (ECG) that, in the investigator's judgment, may interfere with the study evaluation or affect subject safety.
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 |
|---|---|---|
| PegIntron (peginterferon alfa-2b)Also: SCH 54031, PEG-Intron, PegIntron, ViraferonPeg, peginterferon alfa-2bPowder for injection in vial or Redipen (50, 80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 48 weeks | Biological | PegIntron plus Rebetol |
| Rebetol (ribavirin)Also: SCH 18908, Rebetol, REBETOL, ribavirin200 mg capsules, oral, weight based dose of 800-1400 mg, daily for up to 48 weeks | Drug | PegIntron plus Rebetol |
Primary outcome
Number of Subjects Who Have Achieved Sustained Virological Response (SVR) at 24 Weeks Post End of Treatment
Time frame: Up to 48 weeks of treatment plus 24 weeks follow up
Sustained virologic response is defined as a plasma HCV RNA level below Lower Level of Quantitation at 24 weeks post-treatment, which is < 30 IU/mL in this study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 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 PegIntron (peginterferon alfa-2b) and Rebetol (ribavirin) in people with Hepatitis C, Chronic, 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 31 inclusion and 40 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 5 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 4 Aug 2009). 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 Subjects Who Have Achieved Sustained Virological Response (SVR) at 24 Weeks Post End of Treatment (time frame: Up to 48 weeks of treatment plus 24 weeks 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 5 Apr 2017.