A Safety and Tolerability Study of Nitazoxanide in HIV-HCV Treatment Failures

NCT01185028 | Completed Phase 1 Results

• 2 other identifiers: 10018310-CC-0183
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

Brief Summary

Background:

• Chronic hepatitis C (CHC) is a major health problem that particularly affects individuals with human immunodeficiency virus (HIV) infection, and can lead to cirrhosis and liver failure. Standard treatment for people with HIV and CHC is a 48-week course of pegylated-interferon alfa 2a (peg-IFN) and ribavirin (RBV), but better treatments are needed for those who either do not respond to the drugs or who relapse after treatment.
• Nitazoxanide has been approved by the Food and Drug Administration primarily to treat diarrhea caused by parasites, and it has been studied in the treatment of CHC infection. However, it has not been tested in persons infected with HIV and CHC co-infection. Researchers are interested in determining whether nitazoxanide is a safe and tolerable treatment for CHC in individuals with HIV. Objectives: \- To assess the safety and tolerability of using nitazoxanide to treat chronic hepatitis C infection in individuals with HIV who have not responded to standard treatment for hepatitis C. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with both HIV and chronic hepatitis C, and who have either not responded to or relapsed after previous hepatitis C treatment. Design:
• Participants will be screened with a physical examination and medical history; blood and urine tests; imaging studies; possible heart, lung, and psychological tests; and a liver biopsy if one has not been done in the past 3 years.
• Participants will receive nitazoxanide, the medication being studied, to take by mouth for 4 weeks, and will provide blood samples during this time.
• After 4 weeks, participants will receive the first dose of peg-IFN and RBV. Participants will have weekly injections of peg-IFN and continue to take nitazoxanide and RBV by mouth for 48 weeks. Individuals who are slow to respond to this combined CHC treatment (nitazoxanide, peg-IFN, and RBV) by week 12 will continue to have the combined treatment for an extended period, a total of 72 weeks.
• Participants will have study visits to provide blood samples and have other tests two times in the first month of combined treatment, and then at months 2, 3, 4, 7, 10, 13, 19; and month 25 only in participants slow to respond to combined treatment.
• Some participants who are on specific HIV treatment regimens may enroll in a substudy that will require three separate 12-hour visits for repeated blood samples and other tests during the initial 4-week nitazoxanide treatment.

Conditions

Hepatitis C Infection; HIV Infection

Keywords

Chronic HCV; HCV Treatment Nonresponders; HCV Treatment Relapsers; HIV-HCV Co-Infection; Nitazoxanide; Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  Adverse events determined and evaluated by patient reporting and the DAIDS toxicity table.

  1 year and 2 months

Secondary Outcomes (2)

• Sustained Viral Response Rate

  1 year and 2 mos

• Tolerability of Study Drug Measured as Discontinuation.

  1 year and 2 mos

Study Arms (1)

Nitazoxanide With Pegylated Interferon And Ribavirin

EXPERIMENTAL

Nitazoxanide 500mg po bid for 4 wks followed by peg-IFN/Ribavirin/nitazoxanide for 48 weeks

Drug: Nitazoxanide With Pegylated Interferon And Ribavirin

Interventions

Nitazoxanide With Pegylated Interferon And Ribavirin DRUG

Nitazoxanide 500mg po bid for 4 wks followed by peg-IFN/Ribavirin/nitazoxanide for 48 weeks

Nitazoxanide With Pegylated Interferon And Ribavirin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• A participant will be ineligible to participate on this study if any of the following criteria are met:
• A participant cannot be on other experimental therapies (including expanded access/compassionate use of antiretrovirals) for 28 days prior to Day -28 and during his/her participation in this protocol.
• Mixed genotypes (e.g., 1 \& 2, 1 \& 3,1 \& 4). Mixed genotype 1a/1b will be enrolled.
• Has any other known, or clinically suspected, cause of liver disease, including active hepatitis B.
• For participants with cirrhosis, a Child Turcotte Pugh score \> 7, or Child's B or C cirrhosis.
• Has a prothrombin time International Normalized Ratio (PT-INR) \> 2 and is not on chronic anti-coagulation medications, or has a history of hemophilia.
• Has had an organ transplantation other than cornea or hair.
• Has an estimated creatinine clearance (estimated glomerular flow rate) \< 50 mL/min.
• For a participant with higher than 20 ng/mL of alpha-fetoprotein, a negative ultrasound or computerized tomography scan to rule out hepatoma is required for enrollment.
• Has any neoplastic disease EXCEPT for (1) Kaposi's sarcoma not requiring systemic chemotherapy, (2) any non-metastatic skin cancer that has been resected or (3) non-metastatic cervical or anal cancer that has been resected.
• Has evidence of severe cardiac disease (greater than or equal to Grade 3 congestive cardiac failure, symptomatic coronary artery disease, significant arrhythmias, or uncontrolled hypertension) despite intervention or medical therapy.
• Has evidence of severe chronic pulmonary disease with functional impairment or a DLCO (diffusing capacity of the lung for carbon monoxide) less than or equal to 70% at baseline.
• Has a severe psychiatric disorder that would interfere with the adherence to protocol requirements, and that is not stably treated with risk of decompensation.
• Has evidence of autoimmune disorders including inflammatory bowel diseases, psoriasis, and optic neuritis.
• Has evidence of an uncontrolled seizure disorder defined as more than 1 episode of generalized seizure within the past year.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (4)

Family Medical and Counseling Services, SE

Washington D.C., District of Columbia, United States

Location

Unity Health Care/Walker Jones, NE

Washington D.C., District of Columbia, United States

Location

Whitman Walker Clinic, NW

Washington D.C., District of Columbia, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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

• Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002 Nov;36(5 Suppl 1):S35-46. doi: 10.1053/jhep.2002.36806.

  PMID: 12407575 BACKGROUND

• Staples CT Jr, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis. 1999 Jul;29(1):150-4. doi: 10.1086/520144.

  PMID: 10433578 BACKGROUND

MeSH Terms

Conditions

Hepatitis C; HIV Infections

Interventions

nitazoxanide; 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

Results Point of Contact

• Title: Dr. Shyam Kottilil
• Organization: NIAID/NIH

skottilil@niaid.nih.gov

301-435-0936

Study Officials

• Shyamasundaran Kotilil, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2010
• First Posted: August 19, 2010
• Study Start: August 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: October 5, 2021
• Results First Posted: May 15, 2013

Record last verified: 2013-05

Locations

US (4)