Evaluating the Safety of Two Medications to Treat Hepatitis C in People With Thalassemia (The HepC Study)

Hepatitis C Clinical Trial

— HepC  

Official title:

Thalassemia Clinical Research Network - Hepatitis C Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00502788
• Other study ID #: 503
• Secondary ID: U01HL065238U01HL
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2007
• Last updated: March 3, 2014
• Start date: May 2003
• Est. completion date: August 2006

Study information

• Verified date: March 2014
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 44 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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:

1. unstable heart disease that is not controlled by medication

2. serious cerebrovascular disease

3. 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Thalassemia

Intervention

Drug:
• Peginterferon Alfa-2a and Ribavirin
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.
• Ribavirin
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.

Locations

Country	Name	City	State
Canada	Toronto General Hospital, Universty Health Network	Toronto	Ontario
United Kingdom	University College London	London
United States	Weill Medical College of Cornell University	New York	New York
United States	Children's Hospital and Research Center at Oakland	Oakland	California
United States	Children's Hospital Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
New England Research Institutes	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 at Week 72	Yes
Secondary	Mean change in hepatic iron concentration from baseline biopsy to follow-up biopsy; relationship of change to baseline level		Measured at Week 48	Yes
Secondary	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 at Week 72	Yes
Secondary	Cumulate change in deferoxamine dose; evidence for deferoxamine toxicity during hepatitis C treatment		Measured at Week 72	Yes
Secondary	Response rate (undetectable hepatitis C virus RNA)		Measured at Week 24 or 48	Yes
Secondary	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 at Week 72	Yes
Secondary	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 at Week 72	Yes
Secondary	Change in liver inflammation and fibrosis scores from baseline to 48 weeks		Measured at Week 48	Yes
Secondary	Adverse events		Measured at Week 72	Yes
Secondary	Cardiac adverse events, defined as either symptomatic left ventricular dysfunction requiring medication or pathologic arrhythmia requiring medication		Measured at Week 72	Yes
Secondary	Quality of life		Measured at Week 72	No