Hepatitis CPhase 2HepCNCT00502788
Evaluating the Safety of Two Medications to Treat Hepatitis C in People With Thalassemia (The HepC Study)
A Phase 2 study testing Peginterferon Alfa-2a and Ribavirin and Ribavirin in people with Hepatitis C and Thalassemia, run by Carelon Research at 5 sites in 3 countries.
Trial summary
Hepatitis C is one of the most common causes of long-term liver disease in the United States. Ribavirin and peginterferon alfa-2a are two medications that are used to treat hepatitis C infection. Read more about this study
- Who is it for?
- Ages 18 to 44 years
- Conditions the study is for
- Hepatitis C, Thalassemia
- What is being tested?
- Peginterferon Alfa-2a and Ribavirin and Ribavirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 21 participants
- Where
- 5 sitesin 3 countries
- Study dates
- May 2003to Aug 2006
- Phase
- Phase 2
- 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 44 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of thalassemia
- Serum positive for hepatitis C virus RNA by polymerase chain reaction (PCR) test (using the Roche COBAS Amplicor hepatitis C virus test)
- Hepatitis B surface antigen (HBsAg) negative and HIV negative within the 12 months prior to study entry
- Liver biopsy showing histologic evidence of active hepatitis (i.e., at least grade 1 inflammation)
- Willing to use acceptable forms of contraception throughout the study
Who cannot join
- Baseline liver iron concentration greater than 40.00 mg/g dry weight (iron may be chelated and the individual re-screened). All people with liver iron levels greater than 20.00 mg/g dry weight will be permitted to enroll only if their ejection fraction is 55 or greater by echocardiography (ECHO).
- Currently participating in other interventional clinical studies
- Received interferon-alfa therapy within the 6 months prior to study entry
- Liver dysfunction, defined as international normalized ratio (INR) greater than 1.3, albumin less than or equal to 3.5g/dL, or serum bilirubin greater than 4.0 mg/dL that, in the opinion of the investigator, is not due to Gilbert's syndrome or thalassemia-related hemolysis
- Other causes of liver disease (e.g., hereditary hemochromatosis, presumed drug-associated liver disease, Wilson's disease, obesity [body mass index (BMI) greater than 30])
- Major psychiatric illness
Show all 29Show fewer
- Neutrophil count less than or equal to 1500/mm3
- Platelet count less than or equal to 80,000/mm3
- Active alcohol abuse within the 12 months prior to study entry
- Use of illicit drugs (e.g., heroin, cocaine, angel dust) within the 2 years prior to study entry
- Alpha-fetoprotein level greater than 200 ng/mL or evidence of a liver mass lesion by either ultrasound, CT scan, or MRI scan that is suspicious for hepatocellular cancer
- Kidney insufficiency, as defined by a clinically significant abnormal serum creatinine test and confirmed by a creatinine clearance rate of less than 50 mL/min based on 24-hour urine collection. People with an elevated serum creatinine level must undergo a creatinine clearance test.
- Diabetes that, in the opinion of the investigator, is not controlled by diet, an oral hypoglycemic agent, and/or insulin
- Received an organ, limb, or bone marrow transplant
- Requires the use of certain long-term medications such as immunosuppressive medications (e.g., corticosteroids, methotrexate, azathioprine)
- Active systemic autoimmune disorder (e.g., rheumatoid arthritis, systemic lupus)
- Diagnosis or treatment of cancer within the 5 years prior to study entry, except for localized squamous or basal cell cancers treated by local excision
- Any of the following pre-existing conditions that, in the opinion of the investigator, would prevent treatment with interferon and/or ribavirin:
- unstable heart disease that is not controlled by medication
- serious cerebrovascular disease
- serious lung disease
- History of a seizure disorder that has not been well-controlled by anti-seizure medications within the 2 years prior to study entry
- Pregnant or breastfeeding
- Male partners of women who are pregnant
- Any other condition that, in the opinion of the investigator, would prevent study participation
- Known hypersensitivity to any study drug or their components
- Past history of multiple sclerosis, transverse myelitis, optic neuritis, papilledema, chorioretinitis, uveitis, or increased ocular pressure/glaucoma
- Currently taking hematopoietic growth factors
- Currently taking ribavirin
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States3 sites
Weill Medical College of Cornell University
New York, New York, 10021
Children's Hospital and Research Center at Oakland
Oakland, California, 94609
Children's Hospital Philadelphia
Philadelphia, Pennsylvania, 19104
Canada1 site
Toronto General Hospital, Universty Health Network
Toronto, Ontario, M5G 2C4
About this study
Official title: Thalassemia Clinical Research Network - Hepatitis C Clinical Trial
Hepatitis C is one of the most common causes of long-term liver disease in the United States. Ribavirin and peginterferon alfa-2a are two medications that are used to treat hepatitis C infection. The purpose of this study is to evaluate the safety of these two medications in adults with hepatitis C and thalassemia, a type of blood disorder.
Read the detailed description
Hepatitis C is an inflammation of the liver that is caused by infection with the hepatitis C virus. Over time, people may develop liver failure, liver cancer, or cirrhosis, a condition in which the liver may become permanently scarred. Ribavirin and peginterferon alfa-2a are two medications that are used to treat hepatitis C. Ribavirin stops the hepatitis C virus from spreading inside the body, and peginterferon alfa-2a decreases the amount of hepatitis C virus in the body. Individuals with thalassemia, an inherited blood disorder that can cause anemia, often receive regular blood transfusions as part of their treatment. These individuals may have an increased risk of developing hepatitis C as a result of blood transfusions received before routine hepatitis C blood screening was available. Treating thalassemia patients with standard hepatitis C therapy can be difficult because ribavirin can worsen anemia. However, omitting ribavirin then increases the risk of hepatitis C relapse following treatment. The purpose of this study is to evaluate the safety of ribavirin and peginterferon alfa-2a for treating hepatitis C in adults with thalassemia.
This study will enroll adults with thalassemia and long-term hepatitis C. Participants will attend study visits weekly for 4 weeks, every 2 weeks until Week 24, every 4 weeks until Week 48, and then every 6 weeks until Week 72. All participants will receive a peginterferon alfa-2a injection once a week and ribavirin daily. Participants with the hepatitis C genotype 1 will receive 48 weeks of treatment; participants with all other genotypes of the disease will receive 24 weeks of treatment. A liver biopsy will occur at baseline and Week 48. The following will occur at selected study visits: physical exam, blood and urine collection, hearing and vision screening, chest x-ray, heart rate monitoring, and questionnaires to assess hepatitis C symptoms, quality of life, and depression. Participants with liver iron levels greater than 20 mg/g will undergo an echocardiogram ultrasound test every 3 months to monitor the heart.
- Conditions
- Hepatitis C, Thalassemia
- Being tested
- Peginterferon Alfa-2a and Ribavirin, Ribavirin
- Medical subject headings
- Hepatitis C, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peginterferon Alfa-2a and RibavirinDrug
Also called Human recombinant E. Coli, Hoffmann-la Roche
Patients will be treated with alfa-2a and ribavirin as follows:
Peginterferon alfa-2a will be started as a dose of 180 ug subcutaneously once weekly.
RibavirinDrug
Ribavirin will be started at a dose of 800mg daily for those weighing less than or equal to 50 kg, 1000 mg daily for those with body weight 51 to 75 kg and 1200 mg daily for those with body weight > 75 kg. Ribavirin will be given orally in two divided doses. The lower dose has been included because potentially-eligible patients in the TCRN registry have a mean weight of 57 kg.
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of peginterferon alfa-2a and ribavirin in individuals with thalassemia (measured by changes in liver iron stores and development of iron overload-related complications)
Measured: Measured at Week 72
Secondary outcomes (10)
Mean change in hepatic iron concentration from baseline biopsy to follow-up biopsy; relationship of change to baseline level
Measured: Measured at Week 48
Transfusion frequency and volume required to maintain trough Hb 9.0-10.5 g/dL during treatment, as compared to that required in the 6 months prior to hepatitis C treatment
Measured: Measured at Week 72
Cumulate change in deferoxamine dose; evidence for deferoxamine toxicity during hepatitis C treatment
Measured: Measured at Week 72
Response rate (undetectable hepatitis C virus RNA)
Measured: Measured at Week 24 or 48
Sustained virologic response rate (undetectable hepatitis C virus RNA 24 weeks after the end of treatment) and its association with baseline hepatic iron concentration
Measured: Measured at Week 72
Rate of viral clearance from serum in the first 4 weeks of treatment, rate of early virologic response at week 12, and each rate's association with sustained virologic response
Measured: Measured at Week 72
Change in liver inflammation and fibrosis scores from baseline to 48 weeks
Measured: Measured at Week 48
Adverse events
Measured: Measured at Week 72
Cardiac adverse events, defined as either symptomatic left ventricular dysfunction requiring medication or pathologic arrhythmia requiring medication
Measured: Measured at Week 72
Quality of life
Measured: Measured at Week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2007 (estimated)
- Study startMay 2003
- Primary completionJun 2006
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis CStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Maureen Jonas, MD, Study chair, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00502788
- Sponsor's protocol ID
- 503
- Other IDs
- U01HL065238, U01HL065238-07
- Acronym
- HepC
- Status last verified
- Mar 2014
- First submitted
- 16 Jul 2007
- Last updated
- 4 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thalassemia Clinical Research Network - Hepatitis C Clinical Trial
- ClinicalTrials.gov ID
- NCT00502788
- Acronym / sponsor ID
- HepC / 503
- Conditions
- Hepatitis C, Thalassemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- May 2003
- Primary completion
- Jun 2006 (actual)
- Study completion
- Aug 2006 (actual)
- First posted
- 18 Jul 2007 (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.
Hepatitis C is one of the most common causes of long-term liver disease in the United States. Ribavirin and peginterferon alfa-2a are two medications that are used to treat hepatitis C infection. The purpose of this study is to evaluate the safety of these two medications in adults with hepatitis C and thalassemia, a type of blood disorder.
Detailed description
Hepatitis C is an inflammation of the liver that is caused by infection with the hepatitis C virus. Over time, people may develop liver failure, liver cancer, or cirrhosis, a condition in which the liver may become permanently scarred. Ribavirin and peginterferon alfa-2a are two medications that are used to treat hepatitis C. Ribavirin stops the hepatitis C virus from spreading inside the body, and peginterferon alfa-2a decreases the amount of hepatitis C virus in the body. Individuals with thalassemia, an inherited blood disorder that can cause anemia, often receive regular blood transfusions as part of their treatment. These individuals may have an increased risk of developing hepatitis C as a result of blood transfusions received before routine hepatitis C blood screening was available. Treating thalassemia patients with standard hepatitis C therapy can be difficult because ribavirin can worsen anemia. However, omitting ribavirin then increases the risk of hepatitis C relapse following treatment. The purpose of this study is to evaluate the safety of ribavirin and peginterferon alfa-2a for treating hepatitis C in adults with thalassemia.
This study will enroll adults with thalassemia and long-term hepatitis C. Participants will attend study visits weekly for 4 weeks, every 2 weeks until Week 24, every 4 weeks until Week 48, and then every 6 weeks until Week 72. All participants will receive a peginterferon alfa-2a injection once a week and ribavirin daily. Participants with the hepatitis C genotype 1 will receive 48 weeks of treatment; participants with all other genotypes of the disease will receive 24 weeks of treatment. A liver biopsy will occur at baseline and Week 48. The following will occur at selected study visits: physical exam, blood and urine collection, hearing and vision screening, chest x-ray, heart rate monitoring, and questionnaires to assess hepatitis C symptoms, quality of life, and depression. Participants with liver iron levels greater than 20 mg/g will undergo an echocardiogram ultrasound test every 3 months to monitor the heart.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 44 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Diagnosis of thalassemia
- Serum positive for hepatitis C virus RNA by polymerase chain reaction (PCR) test (using the Roche COBAS Amplicor hepatitis C virus test)
- Hepatitis B surface antigen (HBsAg) negative and HIV negative within the 12 months prior to study entry
- Liver biopsy showing histologic evidence of active hepatitis (i.e., at least grade 1 inflammation)
- Willing to use acceptable forms of contraception throughout the study
Key exclusion criteria (29 listed)
- Baseline liver iron concentration greater than 40.00 mg/g dry weight (iron may be chelated and the individual re-screened). All people with liver iron levels greater than 20.00 mg/g dry weight will be permitted to enroll only if their ejection fraction is 55 or greater by echocardiography (ECHO).
- Currently participating in other interventional clinical studies
- Received interferon-alfa therapy within the 6 months prior to study entry
- Liver dysfunction, defined as international normalized ratio (INR) greater than 1.3, albumin less than or equal to 3.5g/dL, or serum bilirubin greater than 4.0 mg/dL that, in the opinion of the investigator, is not due to Gilbert's syndrome or thalassemia-related hemolysis
- Other causes of liver disease (e.g., hereditary hemochromatosis, presumed drug-associated liver disease, Wilson's disease, obesity [body mass index (BMI) greater than 30])
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-2a and RibavirinAlso: Human recombinant E. Coli, Hoffmann-la RochePatients will be treated with alfa-2a and ribavirin as follows: Peginterferon alfa-2a will be started as a dose of 180 ug subcutaneously once weekly. | Drug | – |
| RibavirinRibavirin will be started at a dose of 800mg daily for those weighing less than or equal to 50 kg, 1000 mg daily for those with body weight 51 to 75 kg and 1200 mg daily for those with body weight > 75 kg. Ribavirin will be given orally in two divided doses. The lower dose has been included because potentially-eligible patients in the TCRN registry have a mean weight of 57 kg. | Drug | – |
Primary outcome
Safety of peginterferon alfa-2a and ribavirin in individuals with thalassemia (measured by changes in liver iron stores and development of iron overload-related complications)
Time frame: Measured at Week 72
10 secondary outcomes
Mean change in hepatic iron concentration from baseline biopsy to follow-up biopsy; relationship of change to baseline level
Time frame: Measured at Week 48
Transfusion frequency and volume required to maintain trough Hb 9.0-10.5 g/dL during treatment, as compared to that required in the 6 months prior to hepatitis C treatment
Time frame: Measured at Week 72
Cumulate change in deferoxamine dose; evidence for deferoxamine toxicity during hepatitis C treatment
Time frame: Measured at Week 72
Response rate (undetectable hepatitis C virus RNA)
Time frame: Measured at Week 24 or 48
Sustained virologic response rate (undetectable hepatitis C virus RNA 24 weeks after the end of treatment) and its association with baseline hepatic iron concentration
Time frame: Measured at Week 72
Rate of viral clearance from serum in the first 4 weeks of treatment, rate of early virologic response at week 12, and each rate's association with sustained virologic response
Time frame: Measured at Week 72
Change in liver inflammation and fibrosis scores from baseline to 48 weeks
Time frame: Measured at Week 48
Adverse events
Time frame: Measured at Week 72
Cardiac adverse events, defined as either symptomatic left ventricular dysfunction requiring medication or pathologic arrhythmia requiring medication
Time frame: Measured at Week 72
Quality of life
Time frame: Measured at Week 72
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2014.
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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.
Maureen Jonas, MD study chair
Boston Children's Hospital
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Peginterferon Alfa-2a and Ribavirin and Ribavirin in people with Hepatitis C and Thalassemia, run by Carelon Research at 5 sites in 3 countries.
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 29 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 4 Mar 2014. 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 United States, Canada, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety of peginterferon alfa-2a and ribavirin in individuals with thalassemia (measured by changes in liver iron stores and development of iron overload-related complications) (time frame: Measured at Week 72). 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 4 Mar 2014.