Intrahepatic HCV RNA and Telaprevir Kinetics in Hepatitis C Virus (HCV)

NCT00892697 | Completed Phase 2 Results DMC

• 1 other identifier: 0810010040
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine the decline of virus in the blood and liver in patients treated with telaprevir, pegylated interferon and ribavirin. Fine Needle Aspiration (FNA) procedure will be used to repeatedly sample the liver to enhance the understanding of how the virus decays in the liver in response to treatment with anti-viral compounds and the measurement of the concentration of the drugs in the liver. FNA is an alternative procedure to core needle biopsy in its ability to repeatedly sample the liver with significantly reduced morbidity.

Conditions

Hepatitis C

Keywords

hepatitis C; FNA; intrahepatic

Outcome Measures

Primary Outcomes (1)

• Intrahepatic and Plasma HCV Viral Kinetics

  Intrahepatic viral kinetics, plasma viral kinetics,

  Day-7, Day 1, Day 4,

Secondary Outcomes (1)

• Intrahepatic and Peripheral Pharmacokinetic Assessment of Telaprevir

  Day 1, Day 4, Day 15, Week 8

Study Arms (1)

Arm

EXPERIMENTAL

15 subjects will receive Telaprevir in combination with pegylated interferon alfa-2a and ribavirin

Drug: Telaprevir; Drug: Peginterferon alfa-2a; Drug: Ribavirin

Interventions

Telaprevir DRUG

Fifteen subjects will receive the same treatment: 12 weeks of telaprevir (750 mg q8h) with Peg-IFN- alfa-2a (Pegasys(R)) (180 mcg SQ qwk) and RBV (1200 mg per day if \>75 kg or 1000mg per day if \< 75 kg).

Arm

Peginterferon alfa-2a DRUG

Fifteen subjects will receive the same treatment: 12 weeks of telaprevir (750 mg q8h) with Peg-IFN- alfa-2a (Pegasys(R)) (180 mcg SQ qwk) and RBV (1200 mg per day if \>75 kg or 1000mg per day if \< 75 kg).

Arm

Ribavirin DRUG

Fifteen subjects will receive the same treatment: 12 weeks of telaprevir (750 mg q8h) with Peg-IFN- alfa-2a (Pegasys(R)) (180 mcg SQ qwk) and RBV (1200 mg per day if \>75 kg or 1000mg per day if \< 75 kg).

Arm

Eligibility Criteria

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

You may qualify if:

• Male and female subjects, 18-65 years of age, inclusive.
• Cases will be genotype 1 (confirmed by standard testing). Enrollment of controls will not be restricted by genotype.
• All patients must show evidence of chronic hepatitis C, confirmed by detectable plasma HCV RNA. Chronic disease status must be confirmed by at least one of the following standard criteria:
• Liver biopsy obtained within 24 months of study enrollment demonstrating absence of cirrhosis (stage 0-3) for cases. Enrollment of controls will not be restricted by stage of fibrosis.
• Judged to be in good health on the basis of medical history and physical examination (including vital signs and ECG), with any chronic medical conditions under stable medical control.
• Screening Visit laboratory values must be within the following:
• Laboratory variable: acceptable range
• Absolute neutrophil count: 1200/cmm³
• Platelet count: 90,000/cmm³
• Hemoglobin: within normal range
• HbsAg (screening visit only): seronegative
• HIV1 and 2 Ab (screening visit only): seronegative
• In addition, all other hematology and clinical chemistry must be within normal limits or show no clinically significant abnormalities.
• Subjects (or their female partners) must be not pregnant, planning to become pregnant within the next 72 weeks, or they must be permanently sterile or otherwise of non childbearing potential. They must also not be breastfeeding. If of child-bearing potential, subjects must agree to use 2 effective methods of contraception from screening through 6 months after the last dose of RBV. Male subjects who have a female partner of childbearing potential must agree to use 2 effective methods of contraception from Screening through 7 months after the last dose of RBV unless vasectomized.
• Female subjects must have a negative pregnancy test at all visits (screening and predose Day 1) before the first dose of study drugs.

You may not qualify if:

• Received more than 4 weeks of any approved or investigational drug or drug regimen for the treatment of hepatitis C.
• Any medical contraindications to Peg-IFN alpa-2a or RBV therapy, including any of the following:
• Abnormal thyroid stimulating hormone (TSH) levels or poorly controlled thyroid function
• Evidence of clinically significant cardiac dysfunction;
• History of psychiatric disorders determined by the investigator to contraindicate the use of IFN-based therapy;
• Antinuclear antibody (ANA) titer 1:320;
• History of hemoglobinopathies.
• Patients coinfected with either human immunodeficiency virus (HIV) or hepatitis B virus (HBV).
• Decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices.
• Diagnosed or suspected hepatocellular carcinoma. Alfa-fetoprotein (AFP) during screening must be less than 100 ng/mL.
• For cases, histologic evidence of hepatic cirrhosis on any liver biopsy
• o Most recent liver biopsy must be within 2 years prior to study screening.
• Has taken any of the prohibited medications within 28 days of initiation of therapy.
• A history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include but is not limited to a history of relevant drug or food allergies, history of cardiovascular or central nervous system disease, history or presence of clinically significant illness, or history of mental illness that may affect compliance with study requirements.
• Alcohol abuse or excessive use (in the opinion of the investigator, as judged by medical history) in the last 12 months.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Vertex Pharmaceuticals Incorporated: collaborator

Related Publications (2)

• Talal AH, Dimova RB, Zhang EZ, Jiang M, Penney MS, Sullivan JC, Botfield MC, Chakilam A, Sawant R, Cervini CM, Zeremski M, Jacobson IM, Kwong AD. Telaprevir-based treatment effects on hepatitis C virus in liver and blood. Hepatology. 2014 Dec;60(6):1826-37. doi: 10.1002/hep.27202. Epub 2014 Jul 31.

  PMID: 24811404 RESULT

• Zeremski M, Dimova RB, Benjamin S, Penney MS, Botfield MC, Talal AH. Intrahepatic and Peripheral CXCL10 Expression in Hepatitis C Virus-Infected Patients Treated With Telaprevir, Pegylated Interferon, and Ribavirin. J Infect Dis. 2015 Jun 1;211(11):1795-9. doi: 10.1093/infdis/jiu807. Epub 2014 Dec 15.

  PMID: 25512630 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

telaprevir; 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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Andrew Talal, MD
• Organization: University at Buffalo

ahtalal@buffalo.edu

716-888-4737

Study Officials

• Andrew H. Talal, MD, MPH

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: April 30, 2009
• First Posted: May 4, 2009
• Study Start: May 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 20, 2015
• Results First Posted: March 20, 2015

Record last verified: 2014-12