Trial Outcomes & Findings for Ledipasvir/Sofosbuvir Fixed-Dose Combination With Ribavirin or GS-9669 in Subjects With Chronic Genotype 1 HCV Infection (NCT NCT01984294)
NCT ID: NCT01984294
Last Updated: 2018-11-19
Results Overview
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) 12 weeks following the last dose of study drug.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
101 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2018-11-19
Participant Flow
Participants were enrolled at a total of 1 study site in the United States. The first participant was screened on 29 October 2013. The last study visit occurred on 18 July 2014.
117 participants were screened.
Participant milestones
| Measure |
LDV/SOF+RBV
Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg fixed-dose combination (FDC) tablet once daily plus ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Overall Study
STARTED
|
35
|
32
|
34
|
|
Overall Study
COMPLETED
|
31
|
29
|
27
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
7
|
Reasons for withdrawal
| Measure |
LDV/SOF+RBV
Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg fixed-dose combination (FDC) tablet once daily plus ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Overall Study
Randomized but Never Treated
|
0
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
4
|
2
|
6
|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
Baseline Characteristics
Ledipasvir/Sofosbuvir Fixed-Dose Combination With Ribavirin or GS-9669 in Subjects With Chronic Genotype 1 HCV Infection
Baseline characteristics by cohort
| Measure |
LDV/SOF+RBV
n=35 Participants
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
57 years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
57 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
57 years
STANDARD_DEVIATION 8.2 • n=4 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
4 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
32 participants
n=5 Participants
|
32 participants
n=7 Participants
|
28 participants
n=5 Participants
|
92 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian/ Alaska Native
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
14 participants
n=5 Participants
|
13 participants
n=7 Participants
|
12 participants
n=5 Participants
|
39 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
21 participants
n=5 Participants
|
19 participants
n=7 Participants
|
21 participants
n=5 Participants
|
61 participants
n=4 Participants
|
|
HCV Genotype
Genotype 1a
|
21 participants
n=5 Participants
|
20 participants
n=7 Participants
|
21 participants
n=5 Participants
|
62 participants
n=4 Participants
|
|
HCV Genotype
Genotype 1b
|
14 participants
n=5 Participants
|
12 participants
n=7 Participants
|
12 participants
n=5 Participants
|
38 participants
n=4 Participants
|
|
IL28b Status
CC
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
IL28b Status
CT
|
16 participants
n=5 Participants
|
23 participants
n=7 Participants
|
19 participants
n=5 Participants
|
58 participants
n=4 Participants
|
|
IL28b Status
TT
|
14 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
24 participants
n=4 Participants
|
|
HCV RNA
|
6.0 log10 IU/mL
STANDARD_DEVIATION 0.50 • n=5 Participants
|
6.1 log10 IU/mL
STANDARD_DEVIATION 0.63 • n=7 Participants
|
6.0 log10 IU/mL
STANDARD_DEVIATION 0.57 • n=5 Participants
|
6.0 log10 IU/mL
STANDARD_DEVIATION 0.56 • n=4 Participants
|
|
HCV RNA Category
< 800,000 IU/mL
|
14 participants
n=5 Participants
|
9 participants
n=7 Participants
|
12 participants
n=5 Participants
|
35 participants
n=4 Participants
|
|
HCV RNA Category
≥ 800,000 IU/mL
|
21 participants
n=5 Participants
|
23 participants
n=7 Participants
|
21 participants
n=5 Participants
|
65 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: participants were randomized and received at least one dose of study drug.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) 12 weeks following the last dose of study drug.
Outcome measures
| Measure |
LDV/SOF+RBV
n=35 Participants
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
|
88.6 percentage of participants
|
90.6 percentage of participants
|
81.8 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 8 weeksPopulation: Safety Analysis Set: participants were randomized and received at least one dose of study drug.
Outcome measures
| Measure |
LDV/SOF+RBV
n=35 Participants
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Percentage of Participants Permanently Discontinuing Any Study Drug Due to an Adverse Event
|
0 percentage of participants
|
3.1 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Posttreatment Weeks 2, 4, 8, and 24Population: Full Analysis Set
SVR2, SVR4, SVR8, and SVR24 was defined as HCV RNA \< LLOQ at 2, 4, 8, and 24 weeks following the last dose of study drug, respectively.
Outcome measures
| Measure |
LDV/SOF+RBV
n=35 Participants
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Percentage of Participants With Sustained Virologic Response at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24)
SVR8
|
88.6 percentage of participants
|
90.6 percentage of participants
|
81.8 percentage of participants
|
|
Percentage of Participants With Sustained Virologic Response at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24)
SVR2
|
100.0 percentage of participants
|
100.0 percentage of participants
|
97.0 percentage of participants
|
|
Percentage of Participants With Sustained Virologic Response at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24)
SVR4
|
91.4 percentage of participants
|
90.6 percentage of participants
|
84.8 percentage of participants
|
|
Percentage of Participants With Sustained Virologic Response at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24)
SVR24
|
88.6 percentage of participants
|
90.6 percentage of participants
|
81.8 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 8 weeksPopulation: Full Analysis Set
On-treatment virologic failure was defined as * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
Outcome measures
| Measure |
LDV/SOF+RBV
n=35 Participants
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Percentage of Participants Experiencing On-treatment Virologic Failure
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 24Population: Full Analysis Set
Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) at end of treatment, but did not achieve an SVR.
Outcome measures
| Measure |
LDV/SOF+RBV
n=35 Participants
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) in a divided daily dose for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 Participants
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Percentage of Participants Experiencing Viral Relapse
|
11.4 percentage of participants
|
9.4 percentage of participants
|
18.2 percentage of participants
|
Adverse Events
LDV/SOF+RBV
Serious events: 0 serious events
Other events: 24 other events
Deaths: 0 deaths
LDV/SOF+GS-9669 250 mg
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
LDV/SOF+GS-9669 500 mg
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LDV/SOF+RBV
n=35 participants at risk
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 participants at risk
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 participants at risk
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.1%
1/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.1%
1/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
Other adverse events
| Measure |
LDV/SOF+RBV
n=35 participants at risk
LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks
|
LDV/SOF+GS-9669 250 mg
n=32 participants at risk
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (1 x 250 mg) tablet once daily for 8 weeks
|
LDV/SOF+GS-9669 500 mg
n=33 participants at risk
LDV/SOF 90/400 mg FDC tablet plus GS-9669 (2 x 250 mg) tablets once daily for 8 weeks
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
11.4%
4/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
15.6%
5/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
9.1%
3/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
8.6%
3/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.2%
2/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
21.2%
7/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain
|
2.9%
1/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.1%
2/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Constipation
|
8.6%
3/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.2%
2/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.0%
1/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.1%
2/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Fatigue
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.2%
2/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.0%
1/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Influenza like illness
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.1%
1/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.0%
1/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Asthenia
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Chills
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Pyrexia
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
5/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.2%
2/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
9.1%
3/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.1%
2/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.2%
2/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.0%
1/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
14.3%
5/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.2%
2/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
21.2%
7/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Dizziness
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.1%
1/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Insomnia
|
8.6%
3/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.0%
1/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.6%
3/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.1%
1/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.0%
1/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.7%
2/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
3.1%
1/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.9%
1/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.1%
2/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
|
Vascular disorders
Hot flush
|
0.00%
0/35 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/32 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
6.1%
2/33 • Up to 8 weeks plus 30 days
Safety Analysis Set
|
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