Trial Outcomes & Findings for Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 4 or 5 HCV Infection (NCT NCT02081079)
NCT ID: NCT02081079
Last Updated: 2018-11-19
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
85 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2018-11-19
Participant Flow
Participants were enrolled at study sites in France. The first participant was screened on 07 March 2014. The last study visit occurred on 17 February 2015.
91 participants were screened.
Participant milestones
| Measure |
Genotype 4
Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet administered orally once daily for up to 12 weeks in participants with genotype 4 hepatitis C virus (HCV) infection
|
Genotype 5
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in participants with genotype 5 HCV infection
|
|---|---|---|
|
Overall Study
STARTED
|
44
|
41
|
|
Overall Study
COMPLETED
|
40
|
39
|
|
Overall Study
NOT COMPLETED
|
4
|
2
|
Reasons for withdrawal
| Measure |
Genotype 4
Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet administered orally once daily for up to 12 weeks in participants with genotype 4 hepatitis C virus (HCV) infection
|
Genotype 5
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in participants with genotype 5 HCV infection
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 4 or 5 HCV Infection
Baseline characteristics by cohort
| Measure |
Genotype 4: Treatment-naive
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 4 HCV infection
|
Genotype 4: Treatment-experienced
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 4 HCV infection
|
Genotype 5: Treatment-naive
n=21 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 5 HCV infection
|
Genotype 5: Treatment-experienced
n=20 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 5 HCV infection
|
Total
n=85 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
52 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
50 years
STANDARD_DEVIATION 8.8 • n=7 Participants
|
61 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
64 years
STANDARD_DEVIATION 8.6 • n=4 Participants
|
57 years
STANDARD_DEVIATION 10.8 • n=21 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
36 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
49 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
8 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
19 participants
n=5 Participants
|
17 participants
n=7 Participants
|
21 participants
n=5 Participants
|
20 participants
n=4 Participants
|
77 participants
n=21 Participants
|
|
Region of Enrollment
France
|
22 participants
n=5 Participants
|
22 participants
n=7 Participants
|
21 participants
n=5 Participants
|
20 participants
n=4 Participants
|
85 participants
n=21 Participants
|
|
HCV RNA
|
6.0 log10 copies/mL
STANDARD_DEVIATION 0.40 • n=5 Participants
|
6.3 log10 copies/mL
STANDARD_DEVIATION 0.48 • n=7 Participants
|
6.2 log10 copies/mL
STANDARD_DEVIATION 0.48 • n=5 Participants
|
6.6 log10 copies/mL
STANDARD_DEVIATION 0.39 • n=4 Participants
|
6.3 log10 copies/mL
STANDARD_DEVIATION 0.48 • n=21 Participants
|
|
HCV Genotype
Genotype 4
|
22 participants
n=5 Participants
|
22 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
44 participants
n=21 Participants
|
|
HCV Genotype
Genotype 5
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
21 participants
n=5 Participants
|
20 participants
n=4 Participants
|
41 participants
n=21 Participants
|
|
Cirrhosis Status
Absence
|
21 participants
n=5 Participants
|
13 participants
n=7 Participants
|
18 participants
n=5 Participants
|
14 participants
n=4 Participants
|
66 participants
n=21 Participants
|
|
Cirrhosis Status
Presence
|
1 participants
n=5 Participants
|
9 participants
n=7 Participants
|
3 participants
n=5 Participants
|
6 participants
n=4 Participants
|
19 participants
n=21 Participants
|
|
IL28b Status
CC
|
7 participants
n=5 Participants
|
1 participants
n=7 Participants
|
13 participants
n=5 Participants
|
6 participants
n=4 Participants
|
27 participants
n=21 Participants
|
|
IL28b Status
CT
|
11 participants
n=5 Participants
|
16 participants
n=7 Participants
|
7 participants
n=5 Participants
|
11 participants
n=4 Participants
|
45 participants
n=21 Participants
|
|
IL28b Status
TT
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
13 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: participants with genotype 4 or 5 HCV infection who were enrolled and received at least on 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 4: Treatment-naive
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 4 HCV infection
|
Genotype 4: Treatment-experienced
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 4 HCV infection
|
Genotype 5: Treatment-naive
n=21 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 5 HCV infection
|
Genotype 5: Treatment-experienced
n=20 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 5 HCV infection
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
|
95.5 percentage of participants
|
90.9 percentage of participants
|
95.2 percentage of participants
|
95.0 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: Safety Analysis Set: participants were enrolled and received at least 1 dose of study drug
Outcome measures
| Measure |
Genotype 4: Treatment-naive
n=44 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 4 HCV infection
|
Genotype 4: Treatment-experienced
n=41 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 4 HCV infection
|
Genotype 5: Treatment-naive
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 5 HCV infection
|
Genotype 5: Treatment-experienced
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 5 HCV infection
|
|---|---|---|---|---|
|
Percentage of Participants Who Permanently Discontinued LDV/SOF Due to an Adverse Event
|
0 percentage of participants
|
0 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 |
Genotype 4: Treatment-naive
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 4 HCV infection
|
Genotype 4: Treatment-experienced
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 4 HCV infection
|
Genotype 5: Treatment-naive
n=21 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 5 HCV infection
|
Genotype 5: Treatment-experienced
n=20 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 5 HCV infection
|
|---|---|---|---|---|
|
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4
|
95.5 percentage of participants
|
90.9 percentage of participants
|
95.2 percentage of participants
|
95.0 percentage of participants
|
|
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR24
|
95.5 percentage of participants
|
90.9 percentage of participants
|
95.2 percentage of participants
|
95.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to posttreatment Week 24Population: Full Analysis Set
Virologic failure was defined as either: * 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); or * Relapse: * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment
Outcome measures
| Measure |
Genotype 4: Treatment-naive
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 4 HCV infection
|
Genotype 4: Treatment-experienced
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 4 HCV infection
|
Genotype 5: Treatment-naive
n=21 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 5 HCV infection
|
Genotype 5: Treatment-experienced
n=20 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 5 HCV infection
|
|---|---|---|---|---|
|
Percentage of Patients With Virologic Failure
On-treatment Virologic Failure
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Patients With Virologic Failure
Relapse
|
4.5 percentage of participants
|
9.1 percentage of participants
|
4.8 percentage of participants
|
5.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline; Weeks 2, 4, 8, and 12Population: Full Analysis Set
Outcome measures
| Measure |
Genotype 4: Treatment-naive
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 4 HCV infection
|
Genotype 4: Treatment-experienced
n=22 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 4 HCV infection
|
Genotype 5: Treatment-naive
n=21 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-naive participants with genotype 5 HCV infection
|
Genotype 5: Treatment-experienced
n=20 Participants
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in treatment-experienced participants with genotype 5 HCV infection
|
|---|---|---|---|---|
|
Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12
Change at Week 8
|
-4.88 log10 IU/mL
Standard Deviation 0.401
|
-5.18 log10 IU/mL
Standard Deviation 0.484
|
-5.07 log10 IU/mL
Standard Deviation 0.474
|
-5.45 log10 IU/mL
Standard Deviation 0.387
|
|
Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12
Change at Week 2
|
-4.65 log10 IU/mL
Standard Deviation 0.397
|
-4.77 log10 IU/mL
Standard Deviation 0.495
|
-4.97 log10 IU/mL
Standard Deviation 0.479
|
-4.94 log10 IU/mL
Standard Deviation 0.477
|
|
Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12
Change at Week 4
|
-4.86 log10 IU/mL
Standard Deviation 0.396
|
-5.17 log10 IU/mL
Standard Deviation 0.490
|
-5.07 log10 IU/mL
Standard Deviation 0.474
|
-5.39 log10 IU/mL
Standard Deviation 0.381
|
|
Change From Baseline in HCV RNA at Weeks 2, 4, 8, and 12
Change at Week 12
|
-4.88 log10 IU/mL
Standard Deviation 0.401
|
-5.18 log10 IU/mL
Standard Deviation 0.484
|
-5.07 log10 IU/mL
Standard Deviation 0.474
|
-5.45 log10 IU/mL
Standard Deviation 0.387
|
Adverse Events
Genotype 4
Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths
Genotype 5
Serious events: 1 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Genotype 4
n=44 participants at risk
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in participants with genotype 4 HCV infection
|
Genotype 5
n=41 participants at risk
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in participants with genotype 5 HCV infection
|
|---|---|---|
|
Psychiatric disorders
Depression
|
0.00%
0/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
2.4%
1/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
Other adverse events
| Measure |
Genotype 4
n=44 participants at risk
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in participants with genotype 4 HCV infection
|
Genotype 5
n=41 participants at risk
LDV/SOF (90/400 mg) FDC tablet administered orally once daily for up to 12 weeks in participants with genotype 5 HCV infection
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
6.8%
3/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
2.4%
1/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.8%
3/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Diarrhoea
|
9.1%
4/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Nausea
|
9.1%
4/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
2.4%
1/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
General disorders
Asthenia
|
22.7%
10/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
39.0%
16/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
General disorders
Fatigue
|
20.5%
9/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
9.8%
4/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Injury, poisoning and procedural complications
Wound
|
6.8%
3/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
0.00%
0/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.3%
1/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
4/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
2.4%
1/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.3%
1/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Nervous system disorders
Dizziness
|
0.00%
0/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
7.3%
3/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Nervous system disorders
Headache
|
25.0%
11/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
26.8%
11/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
4/44 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants were randomized and received at least 1 dose of study drug
|
4.9%
2/41 • Up to 12 weeks plus 30 days
Safety Analysis Set: participants 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