Study in HCV-Infected Patients to Determine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of JNJ-47910382

A Phase Ib, Randomized, Double-Blind, Placebo-Controlled Trial in Caucasian Genotype 1 Chronic HCV-Infected Subjects to Determine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Repeated Doses of JNJ-47910382 Given in Different Doses and Dose Regimens

The purpose of this study is to determine the safety, tolerability, pharmacokinetics (what the body does to the medication) and antiviral activity of JNJ-47910382 when administered in different dosing regimens in Caucasian genotype-1 chronic HCV-infected patients.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis C Infection
• Intervention / Treatment: Drug: Placebo; Drug: JNJ-47910382

Detailed Description

This is a Phase Ib, double-blind (neither physician nor patient knows the treatment that the patient receives), randomized (the study drug is assigned by chance), placebo-controlled study in treatment-naïve (someone who has never used drugs for HCV infection), Caucasian genotype 1 chronic HCV-infected patients. The study consists of a screening period, a 9-day treatment period (with 5 days of actual medication intake) and a 4-week follow-up period. The patients will be divided over 4 panels of 10 patients each that will be initiated sequentially. In each panel patients will receive JNJ-47910382 or placebo during 5 consecutive days. JNJ-47910382 or placebo will be administered once daily or twice daily. Within each panel, 5 patients of genotype-1a and 5 patients of genotype-1b will be enrolled. Patients will be randomly assigned to receive active treatment or placebo in such a way that 4 patients of each genotype receive active treatment and 1 subject of each genotype receives placebo. The pharmacokinetic profile of JNJ-47910382 will be assessed in each panel. HCV RNA kinetics (HCV RNA level) and HCV resistance will be studied and biomarkers at the messenger RNA (mRNA), protein and cell level will be explored. The entire study duration for each participant will be approximately four weeks.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany
  • Kiel, Germany
  • Mainz, Germany
  • Münster, Germany
  • Tübingen, Germany
  • Ulm, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic (diagnosis of hepatitis C more than or 6 months before the screening period) HCV infection. Geno- and subtype should be determined or confirmed at screening, and should be 1a or 1b
• Never received (Peg) IFN, RBV or any other approved or investigational antiviral treatment for chronic HCV infection
• HCV RNA level of >100,000 IU/mL at screening (as assessed by standard quantitative in vitro nucleic acid amplification assay)
• Patients having good accessible veins

Exclusion Criteria:

• Evidence of liver cirrhosis or decompensated liver disease
• Patient coinfected with HIV-1 or HIV-2, or hepatitis A or B virus infection, or active tuberculosis at study screening
• Patient infected/coinfected with non-genotype-1 HCV at study screening
• Patient with any cardiac disease at screening, or any active clinically significant disease, or medical history or physical examination findings during screening
• Patient having uncontrolled/unstable disease such as diabetes, epilepsy, a manifest psychiatric disease, thyroid disease or disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel I; Patients will be randomized to receive JNJ-47910382 at a dose of 30 mg or placebo as monotherapy once daily for 5 days.	Drug: Placebo; Form=suspension, route=oral.; Drug: JNJ-47910382; Type=exact number, unit=mg, number=30, 90, 300, 400 or 450, form=suspension, route=oral. Study drug will be administered once or twice daily
Experimental: Panel II; Patients will be randomized to receive JNJ-47910382 at a dose of 90 mg or placebo as monotherapy once daily for 5 days.	Drug: Placebo; Form=suspension, route=oral.; Drug: JNJ-47910382; Type=exact number, unit=mg, number=30, 90, 300, 400 or 450, form=suspension, route=oral. Study drug will be administered once or twice daily
Experimental: Panel III; Patients will be randomized to receive JNJ-47910382 at a dose of 300 mg or placebo as monotherapy once daily for 5 days.	Drug: Placebo; Form=suspension, route=oral.; Drug: JNJ-47910382; Type=exact number, unit=mg, number=30, 90, 300, 400 or 450, form=suspension, route=oral. Study drug will be administered once or twice daily
Experimental: Panel IV; Patients will be randomized to receive JNJ-47910382 at a dose of 400 or 450 mg once daily or 300 mg twice daily (morning dose only on Day 5) or placebo as monotherapy for 5 days.	Drug: Placebo; Form=suspension, route=oral.; Drug: JNJ-47910382; Type=exact number, unit=mg, number=30, 90, 300, 400 or 450, form=suspension, route=oral. Study drug will be administered once or twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of pharmacokinetics of JNJ-47910382	The pharmacokinetics of JNJ-47910382 after 5 consecutive days of administration in chronic HCV-genotype-1 infected patients in different doses and dose regimens will be determined.	Up to 9 Days
Evaluation of the intrinsic antiviral activity of JNJ-47910382	Evaluation of the intrinsic antiviral activity of different doses and dose regimens of JNJ-47910382 in chronic HCV-genotype-1 infected subjects, as measured by the HCV RNA decrease from baseline (Day 1) over time.	Up to 4 weeks
Number of participants with adverse events as a measure of safety and tolerability		Up to 4 weeks

Collaborators and Investigators

• Sponsor: Janssen R&D Ireland

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimate): July 27, 2012

Study Record Updates

• Last Update Posted (Estimate): May 12, 2014
• Last Update Submitted That Met QC Criteria: May 9, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Chronic hepatitis C virus infection; JNJ-47910382; Non-structural protein 5A (NS5A) inhibitor; Caucasian genotype-1
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: CR100760; 47910382HPC1002 (Other Identifier: Janssen R&D Ireland); 2011-005110-10 (EudraCT Number)