Adaptive-design Dose Finding Study to Assess the Antiviral Efficacy and Safety of NIM811 Administered in Combination With Standard of Care (SOC) in Relapsed Hepatitis C Virus 1 (HCV-1) Infected Patients

A Randomized, Adaptive-design, Dose-finding Study to Assess the Antiviral Efficacy and Safety of NIM811 Administered in Combination With the Standard of Care (SOC) in Relapsed Patients Infected With HCV Genotype-1

This is a study designed to identify a dose of NIM811 that has a good safety profile, is well tolerated when co-administered with SOC, and provides a clinically meaningful effect in viral load reduction compared to SOC alone. This information will be used to support doses selected for future studies.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Genotype-1 Relapse
• Intervention / Treatment: Drug: NIM811; Drug: Placebo BID + SOC

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Clayton, New South Wales, Australia
      • Novartis Investigative Site
    • Westmead, New South Wales, Australia
      • Novartis Investigative Site
  • South Australia
    • Wentworthville, South Australia, Australia
      • Novartis Investigative Site
• Belgium
  • Brussels, Belgium
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Germany
  • Frankfurt, Germany
    • Novartis Investigative Site
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Fundacion De Investigacion de Diego
• Spain
  • Barcelona, Spain
    • Novartis Investigative Site
  • Sevilla, Spain
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan
    • Novartis Investigative Site
  • ROC
    • Taipei, ROC, Taiwan
      • Novartis Investigative Site
• United States
  • California
    • San Diego, California, United States, 92105
      • Research and Education Inc.
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
    • Sarasota, Florida, United States, 34243
      • University Hepatitis Center
    • Tampa, Florida, United States, 33607
      • West Wind'r Research & Development LLC
  • Texas
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

• chronic hepatitis C genotype-1
• HCV-RNA should be ≥ 4 x 105 IU/mL at screening
• Recipient of prior long acting interferon and ribavirin treatment for at least 12 weeks, with documented negative serum HCV RNA on treatment, who subsequently becomes serum HCV RNA positive after stopping treatment ("relapser"). Patients must have been off all treatment for at least 3 months prior to start of study (Visit

Exclusion criteria:

• Use of any HCV treatment ≤ 3months prior to study start
• Prior receipt of any investigational anti-HCV therapy which is not IFN or RBV
• Women of child-bearing potential unless they are post-menopausal or use predefined acceptable methods of contraception
• Pregnant or breastfeeding women
• Evidence of cirrhosis, hepatic decompensation, other than HCV liver disease, HBV or HIV infection
• Specified abnormalities in lab values of amongst others hemoglobin, WBC, ANC, platelets
• History of treatment for depression
• Steroid/immunosuppression drug use 3 months prior to study start Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo BID + SOC; Placebo BID + SOC (PEG IFN and RBV)
Experimental: NIM811	Drug: NIM811; BID in various doses (between 100 mg - 600 mg bid) + SOC (PEG IFN and RBV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability of NIM811 dosed daily for 4 weeks in combination with SOC	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To identify a dose of NIM811 which is safe and tolerated and produces in combination with SOC a clinically meaningful improvement over SOC monotherapy in antiviral response Time Frame: 4 weeks	12 weeks
To assess the percentage of patients achieving rapid virologic response (RVR) in patients treated with NIM811 in combination with SOC	4 weeks
To explore the pharmacokinetics and pharmacodynamics of NIM811 given in combination with SOC in patients with chronic hepatitis C genotype-1	3 weeks, 5 weeks
To evaluate the effect of NIM811 given in combination with SOC in patients with chronic hepatitis C genotype-1 on sustained virologic response 12 weeks after cessation of treatment (SVR12)	12 weeks after cessation of treatment

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Lawitz E, Godofsky E, Rouzier R, Marbury T, Nguyen T, Ke J, Huang M, Praestgaard J, Serra D, Evans TG. Safety, pharmacokinetics, and antiviral activity of the cyclophilin inhibitor NIM811 alone or in combination with pegylated interferon in HCV-infected patients receiving 14 days of therapy. Antiviral Res. 2011 Mar;89(3):238-45. doi: 10.1016/j.antiviral.2011.01.003. Epub 2011 Jan 19.

Helpful Links

• Results for CNIM811B2202 from the Novartis Clinical Trials website

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: September 22, 2009
• First Submitted That Met QC Criteria: September 22, 2009
• First Posted (Estimate): September 23, 2009

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: HCV; chronic hepatitis C; chronic hepatitis; relapser; NIM811; chronic hepatitis C genotype-1; HCV-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; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: CNIM811B2202; EUDRACT number: 2009-009995-11