Viral Kinetics in HCV Clearance in Subjects With Hemophilia (HCV/Hemophil)

Viral Kinetic Models of HCV Clearance in Hemophiliacs With Telaprevir

This study will examine viral dynamic responses in subjects with chronic hepatitis C and hemophilia when treated with pegylated interferon + ribavirin and telaprevir.

Study Overview

• Status: Completed
• Conditions: Hemophilia; Chronic Hepatitis C
• Intervention / Treatment: Drug: Ribavirin; Drug: Telaprevir; Drug: PegInterferon

Detailed Description

Previous clinical trials for treatment of chronic hepatitis C have excluded subjects with hemophilia from participating.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Physicians Company

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hemophilia A or B
2. HCV RNA positive (PCR or branched-chain DNA Methods), Genotype 1 (a/b, mixed and unknown subtype)
3. Chronic HCV infection evidenced by HCV serology, HCV RNA or liver enzyme abnormalities present at least 6 months prior to enrollment
4. Liver biopsy or non-invasive marker that permits fibrosis staging within 12 months of enrollment. If a biopsy was not performed within 1 year, non-invasive markers may be utilized during screening period. Cirrhosis is not an exclusion factor
5. Age ≥ 18 years
6. Prior HCV treatment naïve or experienced
7. HCV viral load detectable during screening period
8. Absence of exclusion criteria
9. Sexually active subjects (both male and female) must agree and commit to the use of a medically acceptable form of contraception for the duration of the study and for 6 months following the last dose of study medication. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices or properly used barrier contraception.

Exclusion Criteria:

1. Hemoglobin <11

2. Pregnancy (during screening period or any time during treatment)

   1. females, that are planning to become pregnant or are breastfeeding
   2. males, whose partner is pregnant or is planning to become pregnant
3. HIV Infection

4. Prior History of:

   1. Hepatitis B (HBsAG negative - must have documentation of negative results within one year prior to enrollment or during screening period if not performed in that time window
   2. Homozygotic alpha-1-anti-trypsin (a1AT) deficiency - documentation of a1AT level <80 (at anytime prior to screening). If <80, phenotype testing should not demonstrate zz phenotype. All other phenotypes are not exclusionary,
   3. History of Homozygotic Genetic Hemochromatosis (at anytime prior to enrollment) with evidence of iron overload requiring phlebotomy,
   4. Autoimmune markers (antinuclear antibody (ANA) and/or antismooth muscle antibody (ASMA)) >1:160.
   5. Any other significant liver disease or process (to be determined by the investigator). Non-alcoholic fatty-liver disease (NAFLD) is not an exclusion.
5. History of Decompensated liver disease evidenced by any prior history of hepatic encephalopathy (Grade 2 or higher), ascites, variceal bleeding; Platelet count < 100,000
6. Active thyroid disease (OK if on thyroid replacement with normal thyroid-stimulating hormone (TSH); if TSH abnormal must have normal free thyroid index)
7. Chronic renal insufficiency, defined as creatinine clearance < 50 ml/min. (estimated by Modification of Diet in Renal Disease (MDRD) formula)
8. Life-threatening disease processes that could preclude completion of trial in opinion of investigator.
9. Any condition which the investigator feels will preclude safe completion of the treatment regimen including severe psychiatric disorders, active alcohol or recreational drug abuse.
10. Inability to provide informed consent.
11. Use of systemic corticosteroids or immunomodulatory drugs within 1 month (Nasal steroids are permitted.)
12. Uncontrolled seizure disorder (in opinion of investigator)
13. Concurrent autoimmune processes with active disease that may be exacerbated by interferon-based therapies (e.g. Crohn's Disease, Rheumatoid arthritis) in the opinion of the investigator. Psoriasis permitted if controlled with topical medications at the time of study enrollment.
14. Use of prohibited medications (as described in the telaprevir package insert) within 14 days of the first dose of study medications

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lead-In; Kinetic assessment of response guided treatment per standard of care with PegInterferon + Ribavirin for 4 weeks followed by 12 weeks of PegInterferon + Ribavirin + Telaprevir followed by variable duration of PegInterferon + Ribavirin	Drug: Ribavirin; Drug: Telaprevir; Drug: PegInterferon
Active Comparator: No Lead-in; Kinetic assessment of response guided treatment per standard of care with PegInterferon + Ribavirin + Telaprevir for 12 weeks followed by variable duration of PegIntereron + Ribavirin	Drug: Ribavirin; Drug: Telaprevir; Drug: PegInterferon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sustained Virological Response at Week 12 (SVR12)	Viral kinetic assessment using SVR 12 to either "lead-in" 4 weeks with PegInterferon + Ribavirin or no lead-in, followed by response guided therapy of 24 or 48 weeks based on viral response to treatment. Standard of care treatment stopping rules will be followed with assessment of viral response at week 12 of treatment.	Post-treatment at week 12

Collaborators and Investigators

• Sponsor: Kenneth Sherman
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Genentech, Inc.; Vertex Pharmaceuticals Incorporated
• Investigators: Principal Investigator: Kenneth E Sherman, MD, PhD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: October 5, 2012
• First Submitted That Met QC Criteria: October 9, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Estimate): April 6, 2015
• Last Update Submitted That Met QC Criteria: March 26, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C; Hemophilia
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Hematologic Diseases; Liver Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Blood Coagulation Disorders; Hemophilia A; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: 12053004; R34HL109334 (U.S. NIH Grant/Contract)