Boceprevir Drug Combination for Hepatitis C Treatment in People With and Without HIV

NCT01443923 | Terminated Phase 4 Results

• 2 other identifiers: 11025311-I-0253
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

Background: \- Standard treatment for the hepatitis C virus (HCV) is a combination of the drugs peg-IFN and ribavirin. However, this treatment is not very effective in people with a serious type of HCV (HCV genotype 1) and also in people who have human immunodeficiency virus (HIV) coinfection. Researchers want to add a new drug, boceprevir to see if it can improve treatment results in people with both HCV genotype 1 and HIV. Boceprevir used in combination with peg-IFN and ribavirin has been recently approved for the treatment of people with HCV genotype 1 infection only, and is currently being studied in those with HIV and HCV. Objectives: \- To test boceprevir, peg-IFN, and ribavirin as a treatment for HCV genotype 1 in people with HCV monoinfection compared to those with both HIV and HCV infections. Eligibility:

• Individuals at least 18 years of age who have HCV genotype 1 infection, and have not received interferon treatment for HCV
• Half of the study participants will also have HIV infection. Design:
• Participants will be screened with a medical history and physical exam. They will also have blood and urine tests.
• Participants will also have heart and liver function tests, and answer questions about mood and depression.
• Those in the study will receive ribavirin tablets to take twice a day, and peg-IFN to inject under the skin weekly.
• Two weeks after starting treatment, participants will have blood tests to study the treatment.
• Four weeks after starting treatment, participants will start taking boceprevir three times a day.
• Participants will have regular study visits with blood samples and other tests. The length of therapy will depend on the level of virus detected in the blood at several clinic visits. Those who do not respond well to the medicines at 12 weeks will stop treatment. The full length of treatment is 48 weeks.

Conditions

Hepatitis; HIV/AIDS

Keywords

Hepatitis; Immunological Response; Virological Response; Resistance Mutations; Viral Kinetics; Hepatitis C; HCV

Outcome Measures

Primary Outcomes (1)

• Efficacy, Defined as Sustained Viral Response (SVR) Six Months After the End of Specified Treatment.

  6 months post treatment

Secondary Outcomes (4)

• Change in Early HCV Viral Load Kinetics Between Mono and Co-infected Subjects

  Day 0, Day 7

• Safety and Treatment Outcome Measures Stratified by ESA Use

  6 months

• Proportion of Subjects Who Are Receiving HAART Who Remain With an HIV RNA & lt; 400 Copies/mL and Those With HIV RNA & gt; 400 Copies/mL at End of Treatment

  End of Treatment

• Efficacy (SVR) Rates as Predicted by Viral Response at the End of the 4-week lead-in Therapy With PEG/RBV and Comparison Between HCV Monoinfected and HIV/HCV Coinfected Subjects

  6 months post treatment

Study Arms (2)

1-HCV

ACTIVE COMPARATOR

Hepatitis C Mono-infected

Drug: Boceprevir; Drug: Peg-Interferon-alfa 2B; Drug: Ribavirin

2 HCV/HIV

ACTIVE COMPARATOR

Hepatitis C and HIV co-Infected

Drug: Boceprevir; Drug: Peg-Interferon-alfa 2B; Drug: Ribavirin

Interventions

Boceprevir DRUG

1-HCV; 2 HCV/HIV

Peg-Interferon-alfa 2B DRUG

1-HCV; 2 HCV/HIV

Ribavirin DRUG

1-HCV; 2 HCV/HIV

Eligibility Criteria

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

You may qualify if:

• To be eligible for participation on this protocol, a participant must satisfy all of the following conditions:
• Be greater than or equal to18 years old and have an identifiable primary care provider.
• Have documented chronic HCV infection by demonstration of a positive test for hepatitis C antibody and HCV RNA of 2,000 IU/mL or greater.
• Infected with HCV GT-1 virus.
• If coinfected, have either documentation of HIV-1 infection by licensed enzyme-linked immunosorbent assay (ELISA) confirmed by a Western Blot or history of HIV RNA of 1,000 copies/mL or greater.
• If coinfected, must meet one of the following prior to enrollment:
• If on a stable non-NNRTI or non-PI antiretroviral regimen that HAS NOT changed within the past 6 months, must have an HIV-1 VL of less than 400 copies/mL for at least 3 months; or
• If on a current antiretroviral regimen that HAS changed within the past 6 months, have an HIV-1 VL of less than 50 copies/mL for at least 3 months; or
• Be a long-term nonprogressor as documented in the medica record.
• Have histopathologic features consistent with chronic HCV infection at the time of enrollment. A liver biopsy within 3 years (36 calendar months) prior to screening may be used as the baseline biopsy. Participants can opt out of a liver biopsy if they had one more than 3 years prior and have a contraindication, such as receipt of chronic anticoagulation therapy. Participants with decompensated liver disease are excluded from the study.
• Are na(SqrRoot) ve to prior IFN-based treatment for HCV.
• Have CD4 cell counts greater than or equal to 100 cells/mm(3).
• Willing to have genetic testing.
• Not pregnant or breastfeeding. Serum pregnancy test must be negative at screening for female participants.
• Agree not to become pregnant if a female of childbearing potential while on the study and for at least 6 months after stopping RBV. Because of the potential teratogenic effects of RBV treatment, subjects and their partners must remain abstinent or use two methods of birth control, which may be selected from the following list (oral contraceptive concentrations are decreased, and may not be effective when used during BOC treatment and, therefore, are not included in this list):

You may not qualify if:

• A participant will be ineligible to participate on this study if any of the following criteria are met:
• Use of other experimental therapies (including expanded access/compassionate use of HIV antiretrovirals) within 30 days or 5 half-lives (whichever is longer), prior to enrollment.
• Current use of an efavirenz-based (or other NNRTI) or protease inhibitor HIV antiretroviral regimen.
• Use of any of the following medications within 6 weeks prior to enrollment.
• Alfuzosin (Uroxatral )
• Alprazolam (Xanax )
• Atorvastatin (Lipitor )
• AZT or zidovudine (Retrovir )
• Carbamazepine (Tegretol )
• Cisapride (Propulsid )
• Colchicine (Colcrys ) - If patient has renal or hepatic impairment.
• DDI or didanosine (Videx )
• d4T or stavudine (Zerit )
• Delaviridine (Rescriptor )
• Digoxin (Lanoxin )

Sponsors & Collaborators

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

Study Sites (2)

Unity Health Care, Inc./DC General

Washington D.C., District of Columbia, 20002, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. doi: 10.7326/0003-4819-144-10-200605160-00004.

  PMID: 16702586 BACKGROUND

• Kim WR. The burden of hepatitis C in the United States. Hepatology. 2002 Nov;36(5 Suppl 1):S30-4. doi: 10.1053/jhep.2002.36791.

  PMID: 12407574 BACKGROUND

• Congote LF, Trachewsky D. Qualitative changes in nuclear RNA from rat kidney cortex after aldosterone treatment. Biochem Biophys Res Commun. 1972 Jan 31;46(2):957-63. doi: 10.1016/s0006-291x(72)80234-1. No abstract available.

  PMID: 5057920 BACKGROUND

MeSH Terms

Conditions

Hepatitis; Acquired Immunodeficiency Syndrome; Hepatitis C

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; Ribavirin

Condition Hierarchy (Ancestors)

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

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 Kottilil, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: September 30, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 13, 2015
• Results First Posted: July 13, 2015

Record last verified: 2015-07

Locations

US (2)