Peginterferon Alpha-2a and Ribavirin to Treat Hepatitis C in HIV-infected Patients

NCT00085917 | Completed Phase 2 Results

• 2 other identifiers: 04018704-I-0187
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Peginterferon alpha-2a is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2a. This compound stays in the blood longer than unmodified interferon alpha-2a, causing a higher blood concentration and thus maintaining greater activity against the hepatitis C virus. HIV-infected patients 18 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2-1/2 year study. Candidates are screened with a medical history and physical examination, blood and urine tests, eye examination, chest x-ray, electrocardiogram (EKG), liver ultrasound, and pregnancy test in women who are able to become pregnant. If a recent liver biopsy is not available, this test is done to determine the type and severity of liver disease. The patient is given a sedative before the procedure. Then, the skin in the area over the biopsy site is numbed with a local anesthetic and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. Participants begin treatment with injections under the skin of peginterferon alpha-2a and ribavirin pills by mouth on study day 0. Peginterferon is given either once or twice a week for 4 weeks and then once a week for 44 weeks. Ribavirin is given daily. In addition, patients continue to take all other medications prescribed by their doctor. Clinic visits are scheduled for the following procedures:

• Days 1, 3, 4, 7, 10 and weeks 2, 3, and 4 - Blood tests for safety measures and to measure blood levels of HIV and HCV.
• Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection. In addition, eye examinations are done every 3 months, and pregnancy and thyroid function tests are done several times during the treatment period.
• Week 48 or end of treatment - Treatment stops after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients return to the clinic for a chest x-ray, EKG, blood tests, and abdominal ultrasound. Patients are hospitalized for a repeat liver biopsy.
• Weeks 52, 56, 64 and 72 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection, and a urine pregnancy test in women.

Conditions

Hepatitis C; HIV Infections

Keywords

Pegasys; Ribavirin; Early Virological Response; Hepatitis C; HIV

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sustained Virologic Response (SVR)

  SVR \[ Sustained virological response\] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment.

  72 weeks

Secondary Outcomes (2)

• Number of Participants With Normalization of Liver Enzymes

  week 24, week 48, week 72

• Number of Participants With Adverse Events

  48 weeks

Study Arms (2)

Standard dose arm

ACTIVE COMPARATOR

Pegylated interferon alfa -2a STANDARD DOSE Pegasys 180ug/week

Drug: standard dose pegylated interferon alfa -2a and ribavirin

Double dose arm

EXPERIMENTAL

Double dose pegylated interferon with weight based Ribavirin

Drug: Double dose pegylated interferon with weight based Ribavirin

Interventions

Double dose pegylated interferon with weight based Ribavirin DRUG

pegylated interferon alfa -2a 180ug/twice weekly and weight based ribavirin for 4 weeks then pegylated interferon alfa -2a 180ug/ weekly for the remainder of the treatment

Also known as: Pegasys

Double dose arm

standard dose pegylated interferon alfa -2a and ribavirin DRUG

pegylated interferon alfa -2a 180ug weekly and weight based ribavirin for duration of the treatment

Also known as: pegasys

Standard dose arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to18 years.
• Documentation of HIV-1 infection by licensed ELISA test and confirmed by a Western Blot.
• Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody and on HCV RNA level of 2000 or greater.
• Histopathologic features consistent with chronic hepatitis C on liver biopsy at the time of enrollment. A liver biopsy done for a subject within a year prior to his or her participation may be used as the baseline biopsy.
• Patients with CD4+ cell count greater than 200 cells/mm3 or CD4+ cell percentage greater than 14%.
• Ability to sign informed consent and willingness to comply with the study requirements and clinic policies.
• Serum phosphorus greater than or equal to 2.2 mg/dL and less than or equal to 4.4 (normal range NIH 2.3-4.3 mg/dL).
• Neutrophil count greater than or equal to 1000 cells/mm3.
• Platelets greater than or equal to 50,000/ mm3.
• Hemoglobin greater than or equal to 10.5 mg/dL.
• ALT less than 7 X the NIH upper limit of normal.
• Serum lipase less than 1.5 X the NIH upper limit of normal.
• Not pregnant or breast-feeding. Pregnancy test must be negative within two weeks prior to dosing with study medications.
• If the patient is able to become pregnant then she must use two effective methods of contraception during the study. Effective contraceptive methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter metabolism of hormonal contraception. This is advised on the basis of using ribavirin, which may have a potential teratogenic effect in pregnant women.
• Need to have a primary doctor outside of OP8 or as part of the OP8 training clinic who will be taking care of the patients for their HIV infection and liver disease.

You may not qualify if:

• Patient should not be on other experimental therapies during their participation in this protocol.
• Patients should not have used interferon or peginterferon previously for the treatment of hepatitis C
• Liver histology which, in the opinion of Clinical center pathologist, is consistent with any other co-existent cause of chronic liver disease as defined as chronic hepatitis B with positive HBSag, autoimmune hepatitis with a positive ANA greater than 1 unit or positive anti mitochondrial antibody greater than 1 unit, cholestatic disease with persistent elevation of Alkaline phosphatase, primary biliary cirrhosis or sclerosing cholangitis, Wilson's disease, alpha-1-antitrypsin deficiency, steatohepatitis (alcohol or non alcoholic) with marked steatosis, many Mallory bodies, or extensive zone 3 periportal fibrosis.
• Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC X 100%) of greater than 50% and (2) presence of 3+ or more stainable Iron on liver biopsy according to the study pathologist or a history of previous phlebotomy for Iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. Those who have compound heterozygosity to C282Y and H63D are also not eligible.
• Child Turcotte Pugh score greater than 7.
• PT-INR greater than 2 or history of hemophilia.
• Organ transplant recipient.
• Creatinine clearance less than 50 mL/min.
• Elevated alpha-fetoprotein level (greater than 100 ng/mL).
• Coexisting neoplastic disease except for Kaposi's Sarcoma, any non-metastatic skin cancer that has been resected, non-metastatic cervical or anal cancer that has been resected.
• Severe cardiac or pulmonary decompensation.
• Severe psychiatric disorder that would interfere with the adherence to protocol requirements.
• Preexisting autoimmune disorders including inflammatory bowel diseases, psoriasis, and optic neuritis.
• Preexisting uncontrolled seizure disorder.
• Preexisting pancreatitis.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am. 1994 Sep;23(3):437-55.

  PMID: 7989088 BACKGROUND

• Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, Hollinger FB, Gitnick G, Knodell RG, Perrillo RP, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med. 1992 Dec 31;327(27):1906-11. doi: 10.1056/NEJM199212313272703.

  PMID: 1454085 BACKGROUND

• Koretz RL, Abbey H, Coleman E, Gitnick G. Non-A, non-B post-transfusion hepatitis. Looking back in the second decade. Ann Intern Med. 1993 Jul 15;119(2):110-5. doi: 10.7326/0003-4819-119-2-199307150-00003.

  PMID: 8512159 BACKGROUND

MeSH Terms

Conditions

Hepatitis C; HIV Infections

Interventions

peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Small number of enrolled participants

Results Point of Contact

• Title: John Tierney
• Organization: RCHSPB

john.tierney@nih.gov

301-451-5136

Study Officials

• Shyam Kottilil

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 16, 2004
• First Posted: June 17, 2004
• Study Start: June 1, 2004
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: June 27, 2011
• Results First Posted: June 15, 2011

Record last verified: 2011-06

Locations

US (1)