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

NCT00991289 | Completed Phase 2 Results DMC

• 3 other identifiers: A526910764ACTG A5269
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 18

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.

Conditions

HIV Infection; Hepatitis C Infection

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Complete Early Virologic Response (cEVR)

  Complete early virologic response (cEVR) was defined as undetectable HCV viral load (\<43 IU/ml) at week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).

  Week 16

• Percentage of Participants With Early Virologic Response (EVR)

  Early virologic response (EVR) was defined as undetectable HCV viral load (\<43 IU/ml) at Week 16 or at least a 2-log10 decrease in HCV viral load from study entry at Week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).

  Weeks 0, 16

Secondary Outcomes (9)

• Percentage of Participants With Sustained Virologic Response (SVR)

  24 weeks after treatment discontinuation

• Percentage of Participants With Rapid Virologic Response (RVR)

  Week 8

• Number of Participants With Adverse Events of Grade 2 or Higher

  From study entry to up to week 76

• Change in Hemoglobin Level From Study Entry

  Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76.

• Percent Change in Fasting Insulin Level From Study Entry

  Weeks 0, 16, 28, 52, and 76

Study Arms (1)

NTZ/PEG/RBV

EXPERIMENTAL

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.

Drug: Nitazoxanide (NTZ); Drug: Pegylated interferon alfa-2a (PEG); Drug: Ribavirin (RBV)

Interventions

Nitazoxanide (NTZ) DRUG

500 mg twice daily, taken orally with food

Also known as: Alinia

NTZ/PEG/RBV

Pegylated interferon alfa-2a (PEG) DRUG

180 micrograms via subcutaneous injection once weekly

Also known as: Pegasys

NTZ/PEG/RBV

Ribavirin (RBV) 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.

Also known as: Copegus

NTZ/PEG/RBV

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (18)

Alabama Therapeutics CRS

Birmingham, Alabama, 35294-2050, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, 94304-5350, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

New Jersey Medical School- Adult Clinical Research Ctr. CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

Columbia P&S CRS

New York, New York, 10032, United States

Location

Trillium Health ACTG CRS

Rochester, New York, 14607, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27514, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45267-0405, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, 23298, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (2)

• 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.

  PMID: 19135998 BACKGROUND

• 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.

  PMID: 17888524 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Hepatitis C

Interventions

nitazoxanide; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Marion Peters, MD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2009
• First Posted: October 8, 2009
• Study Start: January 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: January 1, 2012
• Last Updated: November 4, 2021
• Results First Posted: September 27, 2011

Record last verified: 2019-01

Locations

US (17); PR (1)