Nitazoxanide Plus Ribavirin and Peginterferon for Therapy of Treatment Naive HCV Genotype 1 and HIV Coinfected Subjects

NCT ID: NCT00991289

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2012-01-31

Brief Summary

Infection with hepatitis C virus (HCV) can cause liver scarring, or cirrhosis, and this usually occurs more rapidly among people infected with both HCV and human immunodeficiency virus (HIV). People infected with both HCV and HIV have poor response to the current HCV treatments. This phase II pilot study evaluated whether adding a new HCV medication improves response to the current standard HCV treatment with pegylated interferon and ribavirin in people with both HCV and HIV.

Detailed Description

Chronic hepatitis C virus (HCV) is a significant cause of liver scarring, or cirrhosis, and accounts for up to 30% of all liver transplants in the United States. People infected with HIV are at a high risk of coinfection with HCV, and the combination of these two infections appears to accelerate progression to cirrhosis. Current treatment for HCV infection includes a 48-week course of two medications taken together, peginterferon alfa-2a (PEG) and ribavirin (RBV). This combination is only effective in 14% to 29% of people infected with both HIV and HCV genotype 1 (the genotype most common in the United States). Further complicating treatment, antiretrovirals (which are used to treat HIV) and HCV medications can often have high toxicity when taken together, limiting dosing.

Nitazoxanide (NTZ) is a medication currently approved to treat intestinal infections that is being investigated for use in treating HCV. NTZ has few side effects and has been shown to increase effectiveness of HCV treatment when combined with PEG and RBV among HCV monoinfected people. This study will test whether adding NTZ to PEG+RBV regimen for people coinfected with HCV and HIV improves HCV treatment outcomes.

Participation in this study will last up to 76 weeks. At study entry, participants completed a brief physical exam, provided a urine sample for a routine safety test, provided a blood sample, and completed a pregnancy test. Participants then initiated NTZ, which they took twice a day with food for up to a year. After 4 weeks on NTZ, participants completed the second study visit, at which they completed the same assessments as at study entry and were asked about the medications they were taking. At this visit, participants initiated the other two study drugs, PEG and RBV. PEG was delivered via injection weekly and RBV was taken orally twice a day with dose dependent on participant's weight at entry.

Participants took NTZ, PEG and RBV together for up to 48 weeks. During this time, participants completed study visits every 4 weeks until Week 52 and then completed follow-up visits at Weeks 64 and 76. At these visits, participants completed the same assessments as at previous visits, and, at certain weeks, also fasted for 8 hours before blood draw. Additional blood samples were collected and stored at Weeks 4, 8, 16, 52 and 76 in order to do future testing.

Participants who did not achieve an early virologic response to the study treatment (at least a 2-log10 decrease in HCV viral load or undetectable HCV viral load at Week 16), or had detectable HCV viral load at Week 28), stopped study treatment and discontinued study early, at about 20 or 32 weeks, respectively.

Conditions

HIV Infection; Hepatitis C Infection

Keywords

Hepatitis C genotype 1; HCV treatment naive; HCV/HIV coinfection; Antiretroviral; Ribavirin; Pegylated Interferon alfa; Nitazoxanide

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NTZ/PEG/RBV

Participants received nitazoxanide (NTZ) alone for 4 weeks followed by 48 weeks of NTZ with pegylated interferon (PEG) and ribavirin (RBV). Participants who did not achieve early virologic response (EVR) at Week 16 or had detectable hepatitis C virus (HCV) viral load at Week 28 discontinued treatment.

Group Type: EXPERIMENTAL

Nitazoxanide (NTZ)

Intervention Type: DRUG

500 mg twice daily, taken orally with food

Pegylated interferon alfa-2a (PEG)

Intervention Type: DRUG

180 micrograms via subcutaneous injection once weekly

Ribavirin (RBV)

Intervention Type: DRUG

Weight-based dosing; 1,000 mg daily, taken orally, for people weighing less than 75 kg or 1,200 mg for people weighing at least 75 kg.

Interventions

Nitazoxanide (NTZ)

500 mg twice daily, taken orally with food

Intervention Type: DRUG

Pegylated interferon alfa-2a (PEG)

180 micrograms via subcutaneous injection once weekly

Intervention Type: DRUG

Ribavirin (RBV)

Weight-based dosing; 1,000 mg daily, taken orally, for people weighing less than 75 kg or 1,200 mg for people weighing at least 75 kg.

Intervention Type: DRUG

Other Intervention Names

Alinia; Pegasys; Copegus

Eligibility Criteria

Inclusion Criteria

• HIV-1 infection
• Documentation of hepatitis C virus (HCV) genotype 1 infection prior to entry
• Chronic HCV infection for at least 180 days
• CD4+ cell count greater than 200 cells/mm3 obtained within 90 days prior to study entry
• Detectable HCV viral load obtained within 90 days prior to study entry
• Any change in antiretroviral (ARV) regimen, including initiation of antiretroviral therapy (ART), a switch in ART regimen, or a discontinuation of ART, had to have occurred more than 60 days prior to study entry. Breaks in therapy for a maximum of 14 days total during the 60-day period were allowed. Participants not on ART should have had no plans to initiate therapy during the first 24 weeks after study entry. Participants who did start ART did not have to discontinue study treatment. Participants on ART should have planned to remain on the same therapy for at least 12 weeks after study entry. Changes in formulation or dosage were permitted.
• Certain laboratory values obtained within 42 days prior to study entry
• Agreement to use contraception, if participating in sexual activity that could lead to pregnancy, for the duration of study and for 6 months afterward
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase less than or equal to five times the upper limit of normal (ULN)
• Hemoglobin >=11 g/dl for men and >=10 g/dl for women

Exclusion Criteria

• Use of the ARV didanosine (ddI)
• Receipt of any interferon
• Receipt of any therapy for HCV, including ribavirin (RBV) or experimental treatment
• Decompensated cirrhosis
• Currently active or other known causes of significant liver disease, including chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, or homozygous alpha-1 antitrypsin deficiency
• Pregnancy or breastfeeding
• Men with pregnant sexual partners or men planning pregnancy with any sexual partner during treatment or for 24 weeks after treatment completion
• Uncontrolled or active depression, other psychiatric disorder, or any hospitalization within the past 52 weeks that, in the opinion of the site investigator, would prevent participation
• Prior suicide attempt
• Active thyroid disease (use of thyroid hormone replacement therapy permitted if thyroid stimulating hormone [TSH] or free thyroxine [T4] in the normal range)
• History of autoimmune processes, including Crohn's disease, ulcerative colitis, severe psoriasis, or rheumatoid arthritis, that may be exacerbated by interferon use
• Systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry
• Serious illness, including malignancy or active coronary artery disease, within 24 weeks prior to study entry
• Chronic medical condition that, in the site investigator's opinion, might preclude completion of the protocol
• Presence of acute or active opportunistic infections within 24 weeks prior to study entry
• Evidence of hepatocellular carcinoma (HCC) or alpha-fetoprotein level of greater than 50 ng/ml unless an imaging procedure (e.g., computed tomography [CT] scan or magnetic resonance imaging [MRI]) showed no evidence of a hepatic tumor. Each may have been obtained up to 24 weeks before study entry.
• History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency toward hemolysis
• History of major organ transplantation with an existing functional graft
• Known allergy, sensitivity, or any hypersensitivity to components of study drugs or their formulations
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marion Peters, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

Alabama Therapeutics CRS

Birmingham, Alabama, United States

UCLA CARE Center CRS

Los Angeles, California, United States

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, United States

UCSD Antiviral Research Center CRS

San Diego, California, United States

Ucsf Hiv/Aids Crs

San Francisco, California, United States

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, United States

New Jersey Medical School- Adult Clinical Research Ctr. CRS

Newark, New Jersey, United States

Weill Cornell Chelsea CRS

New York, New York, United States

Columbia P&S CRS

New York, New York, United States

Trillium Health ACTG CRS

Rochester, New York, United States

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Cincinnati Clinical Research Site

Cincinnati, Ohio, United States

MetroHealth CRS

Cleveland, Ohio, United States

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, United States

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, United States

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, United States

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB. Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin. Gastroenterology. 2009 Mar;136(3):856-62. doi: 10.1053/j.gastro.2008.11.037. Epub 2008 Nov 19.

Reference Type: BACKGROUND

PMID: 19135998 (View on PubMed)

Korba BE, Montero AB, Farrar K, Gaye K, Mukerjee S, Ayers MS, Rossignol JF. Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antiviral Res. 2008 Jan;77(1):56-63. doi: 10.1016/j.antiviral.2007.08.005. Epub 2007 Sep 4.

Reference Type: BACKGROUND

PMID: 17888524 (View on PubMed)

Other Identifiers

10764

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5269

Identifier Type: OTHER

Identifier Source: secondary_id

A5269

Identifier Type: -

Identifier Source: org_study_id