Hepatitis C, Chronic
Conditions
Brief summary
The purpose of this open-label study is to assess the safety, tolerability, antiviral activity, genotype resistance associated with virological failure, pharmacokinetics and pharmacodynamics of two dose regimens of miravirsen in combination with telaprevir and ribavirin in subjects with hepatitis C virus genotype 1 infection who are null responder to pegylated-interferon alpha and ribavirin.
Interventions
Sponsors
Santaris Pharma A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of chronic hepatitis C genotype 1 infection * BMI 18 and 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects with a Sustained Virological Response at 24 weeks after the end of therapy. | 42 weeks |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of subjects with a Sustained Virological Response at 12 and 48 weeks after the end of therapy. | 66 Weeks |
| The proportion of subjects with undetectable HCV RNA levels at end of treatment. | 18 weeks |
| Change in HCV RNA levels from baseline throughout the study. | 66 Weeks |
| The proportion of subjects who experience virological failure throughout the study. | 66 Weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Urine pharmacokinetics for miravirsen levels will be determined. | Up to 16 Weeks | Urine pharmacokinetics (AUC, Cmax, tmax) for miravirsen levels will be measured in a subset of subjects for up to 24 hours after the last dose of miravirsen. |
| Plasma pharmacokinetics (AUC, Cmax, tmax) for miravirsen, telaprevir, and ribavirin levels will be determined. | 31 Weeks | A single sample will be collected at select study visits for all subjects through Week 31. A subset of subjects will participate in extended PK sampling for up to 5 hours at select study visits and for up to 24 hours after the last dose of miravirsen. |
| Viral resistance analysis at baseline and throughout the study. | 66 Weeks | 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. |
Countries
Puerto Rico, United States
Outcome results
None listed