Trial Outcomes & Findings for Sofosbuvir (GS-7977) in Combination With PEG and Ribavirin for 12 Weeks in Treatment Experienced Subjects With Chronic HCV Infection Genotype 2 or 3 (NCT NCT01808248)
NCT ID: NCT01808248
Last Updated: 2014-09-12
Results Overview
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, \< 15 IU/mL) at 12 weeks after stopping study treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
47 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2014-09-12
Participant Flow
Participants were enrolled at a single site in the United States. The first participant was screened on 18 February 2013. The last participant observation occurred on 06 December 2013.
56 participants were screened; 47 participants were enrolled and treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Participant milestones
| Measure |
SOF+PEG+RBV
Sofosbuvir (SOF) 400 mg tablet once daily + peginterferon alfa 2a (PEG) 180 μg subcutaneous injection once weekly + weight-based ribavirin (RBV; 1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
|
|---|---|
|
Overall Study
STARTED
|
47
|
|
Overall Study
Completed Posttreatment Week 12 Visit
|
45
|
|
Overall Study
COMPLETED
|
42
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
SOF+PEG+RBV
Sofosbuvir (SOF) 400 mg tablet once daily + peginterferon alfa 2a (PEG) 180 μg subcutaneous injection once weekly + weight-based ribavirin (RBV; 1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
|
|---|---|
|
Overall Study
Lack of Efficacy
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Sofosbuvir (GS-7977) in Combination With PEG and Ribavirin for 12 Weeks in Treatment Experienced Subjects With Chronic HCV Infection Genotype 2 or 3
Baseline characteristics by cohort
| Measure |
Genotype 2
n=23 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 hepatitis C virus (HCV) infection.
|
Genotype 3
n=24 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 6.1 • n=5 Participants
|
54 years
STANDARD_DEVIATION 6.9 • n=7 Participants
|
56 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
22 participants
n=5 Participants
|
23 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Liver Cirrhosis
No
|
9 participants
n=5 Participants
|
12 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Liver Cirrhosis
Yes
|
14 participants
n=5 Participants
|
12 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
IL28b Status
CC
|
10 participants
n=5 Participants
|
7 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
IL28b Status
CT
|
10 participants
n=5 Participants
|
15 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
IL28b Status
TT
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
HCV RNA (log10 IU/mL)
|
6.4 log10 IU/mL
STANDARD_DEVIATION 0.66 • n=5 Participants
|
6.0 log10 IU/mL
STANDARD_DEVIATION 0.62 • n=7 Participants
|
6.2 log10 IU/mL
STANDARD_DEVIATION 0.66 • n=5 Participants
|
|
HCV RNA Category
< 6 log10 IU/mL
|
4 participants
n=5 Participants
|
13 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
HCV RNA Category
≥ 6 log10 IU/mL
|
19 participants
n=5 Participants
|
11 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Response to prior HCV treatment
Nonresponse
|
2 participants
n=5 Participants
|
5 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Response to prior HCV treatment
Relapse/Breakthrough
|
21 participants
n=5 Participants
|
19 participants
n=7 Participants
|
40 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: participants with genotype 2 or 3 HCV infection who were enrolled and received at least 1 dose of study drug
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, \< 15 IU/mL) at 12 weeks after stopping study treatment.
Outcome measures
| Measure |
Genotype 2
n=23 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.
|
Genotype 3
n=24 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
|
95.7 percentage of participants
|
83.3 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: Safety Analysis Set: participants enrolled and received at least 1 dose of study drug
The percentage of participants discontinuing any study drug due to an adverse event was summarized.
Outcome measures
| Measure |
Genotype 2
n=47 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.
|
Genotype 3
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
|
|---|---|---|
|
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
|
8.5 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Posttreatment Weeks 4 and 24Population: Full Analysis Set
SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Outcome measures
| Measure |
Genotype 2
n=23 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.
|
Genotype 3
n=24 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4
|
95.7 percentage of participants
|
87.5 percentage of participants
|
|
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR24
|
95.7 percentage of participants
|
83.3 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 12 weeksPopulation: Full Analysis Set
On-treatment virologic failure was defined as: 1. Viral breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or 2. Viral rebound: \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or 3. Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment
Outcome measures
| Measure |
Genotype 2
n=23 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.
|
Genotype 3
n=24 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
|
|---|---|---|
|
Percentage of Participants Experiencing On-treatment Virologic Failure
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 24Population: Participants in the Full Analysis Set with available data were analyzed.
Viral relapse was defined as having HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at the end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.
Outcome measures
| Measure |
Genotype 2
n=22 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.
|
Genotype 3
n=23 Participants
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
|
|---|---|---|
|
Percentage of Participants Experiencing Viral Relapse
|
0 percentage of participants
|
8.7 percentage of participants
|
Adverse Events
SOF+PEG+RBV
Serious events: 4 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SOF+PEG+RBV
n=47 participants at risk
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.1%
1/47 • Up to 12 weeks plus 30 days
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
2.1%
1/47 • Up to 12 weeks plus 30 days
|
|
Hepatobiliary disorders
Cholecystitis
|
2.1%
1/47 • Up to 12 weeks plus 30 days
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
2.1%
1/47 • Up to 12 weeks plus 30 days
|
|
Infections and infestations
Sepsis
|
2.1%
1/47 • Up to 12 weeks plus 30 days
|
Other adverse events
| Measure |
SOF+PEG+RBV
n=47 participants at risk
SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
29.8%
14/47 • Up to 12 weeks plus 30 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
23.4%
11/47 • Up to 12 weeks plus 30 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.9%
7/47 • Up to 12 weeks plus 30 days
|
|
Gastrointestinal disorders
Nausea
|
17.0%
8/47 • Up to 12 weeks plus 30 days
|
|
Gastrointestinal disorders
Diarrhoea
|
10.6%
5/47 • Up to 12 weeks plus 30 days
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
6.4%
3/47 • Up to 12 weeks plus 30 days
|
|
General disorders
Influenza like illness
|
55.3%
26/47 • Up to 12 weeks plus 30 days
|
|
General disorders
Fatigue
|
31.9%
15/47 • Up to 12 weeks plus 30 days
|
|
Infections and infestations
Upper respiratory tract infection
|
8.5%
4/47 • Up to 12 weeks plus 30 days
|
|
Infections and infestations
Sinusitis
|
6.4%
3/47 • Up to 12 weeks plus 30 days
|
|
Metabolism and nutrition disorders
Decreased appetitie
|
8.5%
4/47 • Up to 12 weeks plus 30 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.4%
3/47 • Up to 12 weeks plus 30 days
|
|
Nervous system disorders
Headache
|
14.9%
7/47 • Up to 12 weeks plus 30 days
|
|
Nervous system disorders
Dizziness
|
8.5%
4/47 • Up to 12 weeks plus 30 days
|
|
Psychiatric disorders
Insomnia
|
12.8%
6/47 • Up to 12 weeks plus 30 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.5%
4/47 • Up to 12 weeks plus 30 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.9%
7/47 • Up to 12 weeks plus 30 days
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
6.4%
3/47 • Up to 12 weeks plus 30 days
|
|
Vascular disorders
Hypertension
|
10.6%
5/47 • Up to 12 weeks plus 30 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER