Trial Outcomes & Findings for Efficacy and Safety of Sofosbuvir/Ledipasvir ± Ribavirin in Japanese Participants With Chronic Genotype 1 HCV Infection (NCT NCT01975675)
NCT ID: NCT01975675
Last Updated: 2018-11-16
Results Overview
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
341 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2018-11-16
Participant Flow
Participants were enrolled study sites in Japan. The first participant was screened on 15 October 2013. The last study visit occurred on 22 August 2014.
421 participants were screened.
Participant milestones
| Measure |
LDV/SOF (Treatment Naive)
Treatment-naive participants received ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg fixed-dose combination (FDC) tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus ribavirin (RBV) tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
83
|
83
|
88
|
87
|
|
Overall Study
COMPLETED
|
83
|
82
|
88
|
87
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
LDV/SOF (Treatment Naive)
Treatment-naive participants received ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg fixed-dose combination (FDC) tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus ribavirin (RBV) tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|---|---|
|
Overall Study
Death
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Efficacy and Safety of Sofosbuvir/Ledipasvir ± Ribavirin in Japanese Participants With Chronic Genotype 1 HCV Infection
Baseline characteristics by cohort
| Measure |
LDV/SOF (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF (Treatment Experienced)
n=88 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
n=87 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
Total
n=341 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
59 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
59 years
STANDARD_DEVIATION 10.3 • n=7 Participants
|
61 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
59 years
STANDARD_DEVIATION 8.7 • n=4 Participants
|
59 years
STANDARD_DEVIATION 9.4 • n=21 Participants
|
|
Age, Customized
< 65 years
|
60 participants
n=5 Participants
|
55 participants
n=7 Participants
|
51 participants
n=5 Participants
|
63 participants
n=4 Participants
|
229 participants
n=21 Participants
|
|
Age, Customized
≥ 65 years
|
23 participants
n=5 Participants
|
28 participants
n=7 Participants
|
37 participants
n=5 Participants
|
24 participants
n=4 Participants
|
112 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
199 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
142 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
83 participants
n=5 Participants
|
83 participants
n=7 Participants
|
88 participants
n=5 Participants
|
87 participants
n=4 Participants
|
341 participants
n=21 Participants
|
|
Hepatitis C Virus (HCV) RNA
|
6.6 log10 IU/mL
STANDARD_DEVIATION 0.48 • n=5 Participants
|
6.6 log10 IU/mL
STANDARD_DEVIATION 0.54 • n=7 Participants
|
6.6 log10 IU/mL
STANDARD_DEVIATION 0.55 • n=5 Participants
|
6.5 log10 IU/mL
STANDARD_DEVIATION 0.54 • n=4 Participants
|
6.6 log10 IU/mL
STANDARD_DEVIATION 0.53 • n=21 Participants
|
|
HCV RNA Category
< 800,000 IU/mL
|
6 participants
n=5 Participants
|
8 participants
n=7 Participants
|
10 participants
n=5 Participants
|
13 participants
n=4 Participants
|
37 participants
n=21 Participants
|
|
HCV RNA Category
≥ 800,000 IU/mL
|
77 participants
n=5 Participants
|
75 participants
n=7 Participants
|
78 participants
n=5 Participants
|
74 participants
n=4 Participants
|
304 participants
n=21 Participants
|
|
IL28b Status
CC
|
53 participants
n=5 Participants
|
46 participants
n=7 Participants
|
33 participants
n=5 Participants
|
33 participants
n=4 Participants
|
165 participants
n=21 Participants
|
|
IL28b Status
CT
|
29 participants
n=5 Participants
|
31 participants
n=7 Participants
|
49 participants
n=5 Participants
|
51 participants
n=4 Participants
|
160 participants
n=21 Participants
|
|
IL28b Status
TT
|
1 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
3 participants
n=4 Participants
|
16 participants
n=21 Participants
|
|
Cirrhosis Status
No
|
70 participants
n=5 Participants
|
71 participants
n=7 Participants
|
60 participants
n=5 Participants
|
64 participants
n=4 Participants
|
265 participants
n=21 Participants
|
|
Cirrhosis Status
Yes
|
13 participants
n=5 Participants
|
12 participants
n=7 Participants
|
28 participants
n=5 Participants
|
23 participants
n=4 Participants
|
76 participants
n=21 Participants
|
|
Response to Prior HCV Treatment
Nonresponder
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
29 participants
n=5 Participants
|
28 participants
n=4 Participants
|
NA participants
n=21 Participants
|
|
Response to Prior HCV Treatment
Relapse/Breakthrough
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
44 participants
n=5 Participants
|
44 participants
n=4 Participants
|
NA participants
n=21 Participants
|
|
Response to Prior HCV Treatment
IFN Intolerant
|
NA participants
n=5 Participants
|
NA participants
n=7 Participants
|
15 participants
n=5 Participants
|
15 participants
n=4 Participants
|
NA participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Treatment-naive participants in the Full Analysis Set (randomized, received at least 1 dose of study drug, and had chronic genotype 1 (1a, 1b, or mixed 1a/1b) HCV infection) without cirrhosis were analyzed.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Outcome measures
| Measure |
LDV/SOF (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF (Treatment Naive)
n=70 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
n=71 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), Treatment-naive, Noncirrhotic Participants
|
—
|
100.0 percentage of participants
|
97.2 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Outcome measures
| Measure |
LDV/SOF (Treatment Experienced)
n=88 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
n=87 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12)
|
100.0 percentage of participants
|
100.0 percentage of participants
|
96.4 percentage of participants
|
100.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
Outcome measures
| Measure |
LDV/SOF (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF (Treatment Naive)
n=171 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
n=170 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
|
—
|
0 percentage of participants
|
1.8 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Posttreatment Weeks 4 and 24Population: Full Analysis Set
SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Outcome measures
| Measure |
LDV/SOF (Treatment Experienced)
n=88 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
n=87 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4
|
100.0 percentage of participants
|
100.0 percentage of participants
|
96.4 percentage of participants
|
100.0 percentage of participants
|
|
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR24
|
100.0 percentage of participants
|
100.0 percentage of participants
|
96.4 percentage of participants
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 24Population: Full Analysis Set
Virologic failure was defined as On-treatment virologic failure: * 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) Virologic relapse: \- Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.
Outcome measures
| Measure |
LDV/SOF (Treatment Experienced)
n=88 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Naive)
n=83 Participants
Treatment-naive participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
LDV/SOF+RBV (Treatment Experienced)
n=87 Participants
Treatment-experienced participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|---|---|
|
Percentage of Participants Experiencing Virologic Failure
On-treatment virologic failure
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Experiencing Virologic Failure
Virologic relapse
|
0 percentage of participants
|
0 percentage of participants
|
1.2 percentage of participants
|
0 percentage of participants
|
Adverse Events
LDV/SOF
Serious events: 3 serious events
Other events: 77 other events
Deaths: 0 deaths
LDV/SOF+RBV
Serious events: 2 serious events
Other events: 90 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LDV/SOF
n=171 participants at risk
Participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV
n=170 participants at risk
Participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
0.59%
1/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
0.59%
1/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.58%
1/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
0.00%
0/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.58%
1/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
0.00%
0/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
0.58%
1/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
0.00%
0/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
Other adverse events
| Measure |
LDV/SOF
n=171 participants at risk
Participants received LDV/SOF 90/400 mg FDC tablet once daily for up to 12 weeks.
|
LDV/SOF+RBV
n=170 participants at risk
Participants received LDV/SOF 90/400 mg FDC tablet once daily, plus RBV tablets (600 to 1000 mg daily based on weight) in a divided daily dose for up to 12 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.8%
3/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
13.5%
23/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Nausea
|
2.9%
5/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
5.3%
9/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Stomatitis
|
3.5%
6/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
5.9%
10/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
General disorders
Malaise
|
5.3%
9/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
5.3%
9/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Infections and infestations
Nasopharyngitis
|
29.2%
50/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
23.5%
40/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Nervous system disorders
Headache
|
7.0%
12/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
8.8%
15/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.5%
6/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
7.6%
13/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.9%
5/171 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
8.2%
14/170 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug
|
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