Trial Outcomes & Findings for Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination Tablet With Ribavirin for 12 Weeks in Treatment-naive Adults With Chronic HCV Genotype 3 Infection (NCT NCT02413593)
NCT ID: NCT02413593
Last Updated: 2018-11-16
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
111 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2018-11-16
Participant Flow
Participants were enrolled at study sites in Canada. The first participant was screened on 15 April 2015. The last study visit occurred on 08 January 2016.
127 participants were screened.
Participant milestones
| Measure |
LDV/SOF+RBV
Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Overall Study
STARTED
|
111
|
|
Overall Study
COMPLETED
|
107
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
LDV/SOF+RBV
Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination Tablet With Ribavirin for 12 Weeks in Treatment-naive Adults With Chronic HCV Genotype 3 Infection
Baseline characteristics by cohort
| Measure |
LDV/SOF+RBV
n=111 Participants
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Age, Continuous
|
48 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
111 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
78 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
HCV Genotype
Genotype 3 (no confirmed subtype)
|
3 Participants
n=5 Participants
|
|
HCV Genotype
Genotype 3a
|
105 Participants
n=5 Participants
|
|
HCV Genotype
Genotype 3b
|
3 Participants
n=5 Participants
|
|
Cirrhosis Status
Absent
|
70 Participants
n=5 Participants
|
|
Cirrhosis Status
Present
|
39 Participants
n=5 Participants
|
|
Cirrhosis Status
Missing
|
2 Participants
n=5 Participants
|
|
IL28b Status
CC
|
40 Participants
n=5 Participants
|
|
IL28b Status
CT
|
56 Participants
n=5 Participants
|
|
IL28b Status
TT
|
13 Participants
n=5 Participants
|
|
IL28b Status
Missing
|
2 Participants
n=5 Participants
|
|
HCV RNA
|
6.2 log10 IU/mL
STANDARD_DEVIATION 0.66 • n=5 Participants
|
|
HCV RNA Category
< 800,000 IU/mL
|
35 Participants
n=5 Participants
|
|
HCV RNA Category
≥ 800,000 IU/mL
|
76 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: all enrolled participants who 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 |
LDV/SOF+RBV
n=111 Participants
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
|
89.2 percentage of participants
Interval 81.9 to 94.3
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: Safety Analysis Set
Outcome measures
| Measure |
LDV/SOF+RBV
n=111 Participants
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
|
0.9 percentage of participants
|
SECONDARY outcome
Timeframe: Posttreatment Week 4Population: Full Analysis Set
SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.
Outcome measures
| Measure |
LDV/SOF+RBV
n=111 Participants
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
|
91.9 percentage of participants
Interval 85.2 to 96.2
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 4, 8, and 12Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
LDV/SOF+RBV
n=111 Participants
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8 and 12
Week 1
|
20.7 percentage of participants
Interval 13.6 to 29.5
|
|
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8 and 12
Week 2
|
64.9 percentage of participants
Interval 55.2 to 73.7
|
|
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8 and 12
Week 4
|
97.3 percentage of participants
Interval 92.3 to 99.4
|
|
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8 and 12
Week 8
|
100.0 percentage of participants
Interval 96.7 to 100.0
|
|
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8 and 12
Week 12
|
99.1 percentage of participants
Interval 95.0 to 100.0
|
SECONDARY outcome
Timeframe: Baseline; Weeks 1, 2, 4, 8, and 12Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
LDV/SOF+RBV
n=111 Participants
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
Change at Week 1
|
-4.33 log10 IU/mL
Standard Deviation 0.572
|
|
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
Change at Week 2
|
-4.85 log10 IU/mL
Standard Deviation 0.659
|
|
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
Change at Week 4
|
-5.05 log10 IU/mL
Standard Deviation 0.664
|
|
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
Change at Week 8
|
-5.06 log10 IU/mL
Standard Deviation 0.664
|
|
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12
Change at Week 12
|
-5.06 log10 IU/mL
Standard Deviation 0.669
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 12Population: 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+RBV
n=111 Participants
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Percentage of Participants With Virologic Failure
|
7.2 percentage of participants
|
Adverse Events
LDV/SOF+RBV
Serious events: 4 serious events
Other events: 89 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LDV/SOF+RBV
n=111 participants at risk
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.90%
1/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.90%
1/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer
|
0.90%
1/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Psychiatric disorders
Homicidal ideation
|
0.90%
1/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Psychiatric disorders
Suicidal ideation
|
0.90%
1/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Vascular disorders
Hypertensive crisis
|
0.90%
1/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
Other adverse events
| Measure |
LDV/SOF+RBV
n=111 participants at risk
LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
5.4%
6/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Gastrointestinal disorders
Diarrhoea
|
9.9%
11/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
22.5%
25/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Gastrointestinal disorders
Vomiting
|
6.3%
7/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
General disorders
Fatigue
|
51.4%
57/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Infections and infestations
Nasopharyngitis
|
7.2%
8/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.3%
7/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Nervous system disorders
Dizziness
|
11.7%
13/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
36.0%
40/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Psychiatric disorders
Depression
|
5.4%
6/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Psychiatric disorders
Insomnia
|
17.1%
19/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Psychiatric disorders
Irritability
|
9.9%
11/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.2%
8/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.4%
6/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.4%
6/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.3%
7/111 • Baseline to 30 days after last dose of study drug (up to 12 weeks plus 30 days)
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.3%
7/111 • Baseline to 30 days after last dose of study drug (up to 12 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