Hepatitis C, Chronic
Conditions
Keywords
HCV Genotype 1, Hepatitis C Virus Genotype 1, HCV, TVR
Brief summary
This is an open-label, multi center study of treatment-naive non-cirrhotic subjects with genotype 1 chronic Hepatitis C Virus. All subjects will receive telaprevir (TVR) in combination with sofosbuvir (SOF) for 12 weeks.
Detailed description
Starting on Day 1 and for up to 12 weeks, you will receive Telaprevir (TVR) and Sofosbuvir (SOF). You will take one (1) 400 mg tablet of SOF and 3 tablets (1125 mg each) of TVR. You should take these together by mouth every morning. You will take another 3 tablets (1125 mg each) of TVR by mouth 12 hours after you take your morning dose.
Interventions
DRUGTelaprevir and Sofosbuvir
All subjects will have time to read and discuss IRB approved consent form prior to any study procedures. Following proper consenting, subjects will undergo physical exam including ECG and bloodwork prior to baseline visit. Subjects will return for research visits (vitals, collection of AEs, bloodwork, drug accountability) on Day 3, Weeks 1, 2, 3, 4, 6, 8, 10 and 12 of treatment and 4, 12, and 24 weeks after end of treatment. PK samples will be collected at week 2 and week 10.
Sponsors
Vertex Pharmaceuticals Incorporated
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide informed consent * BMI (Body Mass Index) ≥ 18 kg/m2 * HCV RNA quantifiable at screening and \>1,000 IU/ml * HCV treatment Naïve * HCV genotype 1 * 7\. Confirmation of chronic HCV infection documented by either: A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or A liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection
Exclusion criteria
* Current or prior history of any of the following: Clinically-significant illness Cirrhosis 2. Screening ECG with clinically significant abnormalities 1. ALT \> 10 x the upper limit of normal (ULN) 2. AST \> 10 x ULN 3. Direct bilirubin \> 1.5 x ULN 4. Platelets \< 150,000/μL 5. HbA1c \> 7.5% 6. Creatinine clearance (CLcr) \< 60 mL /min, as calculated by the Cockcroft-Gault equation 7. Hemoglobin \< 11 g/dL for female subjects; \< 12 g/dL for male subjects. 8. Albumin \< 3.1 g/dL 9. INR \> 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR 4. Prior exposure to any approved or experimental HCV-specific direct-acting 5\. Pregnant or nursing female or male with pregnant female partner. 6\. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis). 7\. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events Leading to Discontinuation of Both Telaprevir and Sofosbuvir Among Subjects Treated With Telaprevir and Sofosbuvir | 12 weeks-January 3, 2014- April 10, 2014 | Study drug adherence and adverse events were collected on all enrolled subjects and graded using the DAIDS scale. Any adverse events leading to discontinuation of both Telaprevir and Sofosbuvir were collected and are hereby reported. |
| Safety of Telaprevir and Sofosbuvir When Dosed in Combination for 12 Weeks | 1/3/2014-4/10/2014 | The number of subjects who experienced Grade 3 anemia. Complete blood count was collected at baseline, week 2, week 4, week 8, week 12, week 18, and week 24. Incidence of moderate anemia (Grade 3) observed in the study treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize Steady State of Sofosbuvir Active SOF Metabolite, GS-331007 | 1/17/2014-3/26/2014 | Sparse Pharmokinetic blood samples were collected at Week 2 and Week 10 (prior to daily dose) in patients treated with Telaprevir and Sofosbuvir. |
| Proportion of Subjects Who Achieve Undetectable Hepatitis C Virus RNA at 12 Weeks After Completing Study Drug Regimen | 6/16/2014-7/2/2014 | Plasma HCV RNA levels were assessed using the COBAS TaqMan HCV RNA assay test (v2.0; Roche Diagnostics, Indianapolis, IN, USA; LLOQ=25 IU/mL;limit of detection =15 IU/mL) |
| Proportion of Subjects With Viral Relapse | 1/3/2014-9/8/2014 | Defined as Subjects who have undetectable HCV RNA at end of treatment, and confirmed detectable HCV RNA between end of treatment and SVR12 planned assessment time point. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Sustained Virologic Response at 4 Weeks After Completion of Last Dose | 4/22/2014-5/6/2014 | Subjects who complete assigned treatment and have undetectable HCV RNA at 12 weeks after the last planned dose of study treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Telaprevir and Sofosbuvir All subjects will receive Telaprevir twice a day, 1125mg capsule and Sofosbuvir 400 mg capsule once daily. Both will be given for 12 weeks.
Telaprevir and Sofosbuvir: All subjects will have an ECG performed. Then they will receive Telaprevir twice a day, 1125mg capsule and Sofosbuvir 400 mg capsule once daily. Both will be given for 12 weeks. In addition, PK samples will be collected at week 2 and week 10. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Telaprevir and Sofosbuvir |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 51 years |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Frequency of Adverse Events Leading to Discontinuation of Both Telaprevir and Sofosbuvir Among Subjects Treated With Telaprevir and Sofosbuvir
Study drug adherence and adverse events were collected on all enrolled subjects and graded using the DAIDS scale. Any adverse events leading to discontinuation of both Telaprevir and Sofosbuvir were collected and are hereby reported.
Time frame: 12 weeks-January 3, 2014- April 10, 2014
Population: Non-cirrhotic Hepatitis C Genotype 1 infected subjects, naive to previous Hepatitis C treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telaprevir and Sofosbuvir | Frequency of Adverse Events Leading to Discontinuation of Both Telaprevir and Sofosbuvir Among Subjects Treated With Telaprevir and Sofosbuvir | 0 participants |
Primary
Safety of Telaprevir and Sofosbuvir When Dosed in Combination for 12 Weeks
The number of subjects who experienced Grade 3 anemia. Complete blood count was collected at baseline, week 2, week 4, week 8, week 12, week 18, and week 24. Incidence of moderate anemia (Grade 3) observed in the study treatment period.
Time frame: 1/3/2014-4/10/2014
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telaprevir and Sofosbuvir | Safety of Telaprevir and Sofosbuvir When Dosed in Combination for 12 Weeks | 1 participants |
Secondary
Characterize Steady State of Sofosbuvir Active SOF Metabolite, GS-331007
Sparse Pharmokinetic blood samples were collected at Week 2 and Week 10 (prior to daily dose) in patients treated with Telaprevir and Sofosbuvir.
Time frame: 1/17/2014-3/26/2014
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Telaprevir and Sofosbuvir | Characterize Steady State of Sofosbuvir Active SOF Metabolite, GS-331007 | Pre-Dose Trough Level Metabolite GS-331007 Wk 2 | 593 ng/mL | Standard Deviation 181 |
| Telaprevir and Sofosbuvir | Characterize Steady State of Sofosbuvir Active SOF Metabolite, GS-331007 | Pre-Dose Trough Level GS-331007 Wk 10 | 619 ng/mL | Standard Deviation 216 |
Secondary
Proportion of Subjects Who Achieve Undetectable Hepatitis C Virus RNA at 12 Weeks After Completing Study Drug Regimen
Plasma HCV RNA levels were assessed using the COBAS TaqMan HCV RNA assay test (v2.0; Roche Diagnostics, Indianapolis, IN, USA; LLOQ=25 IU/mL;limit of detection =15 IU/mL)
Time frame: 6/16/2014-7/2/2014
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telaprevir and Sofosbuvir | Proportion of Subjects Who Achieve Undetectable Hepatitis C Virus RNA at 12 Weeks After Completing Study Drug Regimen | 19 participants |
Secondary
Proportion of Subjects With Viral Relapse
Defined as Subjects who have undetectable HCV RNA at end of treatment, and confirmed detectable HCV RNA between end of treatment and SVR12 planned assessment time point.
Time frame: 1/3/2014-9/8/2014
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telaprevir and Sofosbuvir | Proportion of Subjects With Viral Relapse | 1 participants |
Other Pre-specified
Number of Subjects With Sustained Virologic Response at 4 Weeks After Completion of Last Dose
Subjects who complete assigned treatment and have undetectable HCV RNA at 12 weeks after the last planned dose of study treatment
Time frame: 4/22/2014-5/6/2014
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telaprevir and Sofosbuvir | Number of Subjects With Sustained Virologic Response at 4 Weeks After Completion of Last Dose | 19 participants |