Miravirsen Study in Null Responder to Pegylated Interferon Alpha Plus Ribavirin Subjects With Chronic Hepatitis C

A Phase 2, Open-Label, Clinical Trial of Miravirsen Sodium in Null Responder to Pegylated-Interferon Alpha Plus Ribavirin Subjects With Chronic Hepatitis C (CHC) Virus Genotype 1 Infection

The purpose of this open-label study is to assess the safety, antiviral activity, and pharmacokinetics of 9 subcutaneous injections of miravirsen monotherapy (5 weekly doses over 5 weeks, followed by a further 4 doses once every other week over 7 weeks) over a total of 12 weeks of treatment. The subjects enrolled in this study are chronically infected with HCV genotype 1 and are null responders to treatment with peg IFNα/RBV therapy.

Study Overview

• Status: Unknown
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Miravirsen sodium

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigation de Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of chronic hepatitis C
• HCV genotype 1
• BMI 18-38 kg/m2
• Null responder to pegylated interferon alpha and ribavirin

Exclusion Criteria:

• Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
• Significant liver disease in addition to hepatitis C
• Decompensated liver disease medical history or current clinical features
• Histologic evidence of hepatic cirrhosis
• Concurrent clinically significant medical diagnosis (other than CHC)
• Concurrent social conditions (e.g. drugs of abuse, alcohol excess, poor living accommodation)
• Clinically significant illness within 30 days preceding entry into the study
• Participated in an investigational drug study within 30 days or 5 half-lives, whichever is longer, prior to the start of study medication
• History of clinically significant allergic drug reactions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Miravirsen sodium; Miravirsen will be dosed as single subcutaneous injections. Subjects will receive 5 weekly doses at 7 mg/kg then 4 every other week doses at 5 mg/kg.	Drug: Miravirsen sodium; Subcutaneous injection; Other Names: SPC3649

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of subjects with sustained virological response 24 weeks after the end of therapy.	36 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of subjects with a sustained virological response 12 and 48 weeks after the end of therapy.	60 weeks
The proportion of subjects with undetectable HCV RNA levels at the end of treatment.	12 weeks
Change in HCV RNA levels from baseline throughout the study.	60 weeks
The proportion of subjects who experience virological failure throughout the study.	60 weeks
Safety will be assessed by evaluation of adverse events, physical examinations, vital signs, 12-lead ECGs, and laboratory assessments (clinical chemistry, hematology, urinalysis).	60 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral resistance analysis at baseline and throughout the study.	The miR-122 seed sites in HCV RNA from subjects at baseline and following viral breakthrough or relapse will be subjected to genotypic sequence analysis.	60 weeks
Plasma pharmacokinetics	Plasma PK for miravirsen levels will be determined for up to 2 hours post-dose on Day 1, up to 24 hours post-dose on Days 29 and 84, and pre-dose for all other treatment period visits. Additionally, plasma PK will be evaluated at all follow-up visits through Week 28.	28 weeks
Urine pharmacokinetics		Up to 24 hours post-dose on Day 29 and Day 84

Collaborators and Investigators

• Sponsor: Santaris Pharma A/S
• Investigators: Principal Investigator: Maribel Rodriguez-Torres, MD, Fundacion de Investgacion de Diego

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Anticipated): January 1, 2014
• Study Completion (Anticipated): April 1, 2014

Study Registration Dates

• First Submitted: November 12, 2012
• First Submitted That Met QC Criteria: November 12, 2012
• First Posted (Estimate): November 16, 2012

Study Record Updates

• Last Update Posted (Estimate): January 6, 2014
• Last Update Submitted That Met QC Criteria: January 3, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Chronic hepatitis C; Hepatitis C; Antisense; miR-122 antagonist; host factor
• 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: SPC3649-207