Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Ledipasvir and sofosbuvir is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) [see Dosage and Administration (2.2 and 2.3) and Clinical Studies (14) ]: genotype 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis genotype 1 infection with decompensated cirrhosis, for use in combination with ribavirin genotype 1 or 4… FDA label
Also known as LDV, Harvoni®, GS-7977, PSI-7977, GS-5885
LDV/SOF · 38 trials · 14 indications
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.
SVR12 was defined as HCV RNA level \< the lower limit of quantification (LLOQ, ie, \< 25 copies/mL) 12 weeks after last dose of study drug.
To evaluate the efficacy of treatment with ledipasvir (LDV)/sofosbuvir (SOF) FDC for 6 weeks in patients with acute genotype 1 HCV infection as measured by the proportion of subjects with sustained viral response (HCV RNA \< LLOQ TND) 12 weeks after discontinuation of therapy (SVR 12) using COBAS TaqMan Realtime PCR.
To evaluate the safety and tolerability of LDV/SOF FDC-containing regimens administered for up to 6 weeks in patients with acute genotype 1 HCV infection as measured by the frequency of AEs and SAEs assessed at end of treatment, 12 and 24 weeks after end of treatment.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG) was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal choline was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
MRS was analyzed in the LCmodel program and measured in 3 specific areas of brain (basal ganglia, frontal cortex, and dorsolateral prefrontal cortex). The cerebral metabolic signal myoinositol was analyzed. Spectroscopy results are expressed as metabolic ratio with creatine used as the control metabolite, so there are no units of measure.
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Memory T Score: visuospatial memory immediate total T score (BVMTTTs), visuospatial memory delayed T score (BVMTTDTS), verbal memory total T score (HVLTTTS), and verbal memory delayed T score (HVLTDTS). For this analysis, Memory T Score (total) ranged from 80 to 320, with higher scores indicating better memory.
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Attention Scaled Score: forward digit span scaled score (FSCORESS), backward digit span scaled score (BSCORESS), and symbol span total scaled score (SYMSPSS). For this analysis, Attention Scaled Score (total) ranged from 3 to 57, with higher scores indicating better working memory capacity and control.
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 1 Processing Speed score: symbol search total scaled score (SSSS) and trails A total raw score (TrailARS). For this analysis, Executive 1 Processing Speed score (total) ranged from 1 to 108, with lower scores indicating better executive control.
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Executive 2 Conceptual Shift and Initiation score: trails B raw score (TrailBRS), age \& education adjusted raw score (FASadj), color word interference score (time) (CWTrial3), and color word interference/shifting score (time) (CWTrial4). For this analysis, Executive 2 Conceptual Shift and Initiation score (total) ranged from 1 to 570, with lower scores indicating better executive control.
Neurocognitive function tests were administered by a licensed clinician. The sum of following neurocognitive test scores was used to determine the Motor score: dominant hand fine motor speed (time) (DomHtot) and non-dominant hand fine motor speed (time) (nonDOMHtot). For this analysis, Motor score (total) ranged from 20 to 600, with lower scores indicating better fine motor speed.
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized.
To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
To evaluate antiviral efficacy as measured by sustained virologic response (defined as HCV RNA \< lower limit of quantitation 24-weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin.
To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as plasma HCV RNA \< Lower Limit of Quantification (LLoQ) at 24 weeks post-treatment) of response guided therapy (RGT) with GS-5885 + GS-9451 + PEG/RBV, or GS-5885 + PEG/RBV.
To evaluate antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< Lower Limit of Quantification (LLoQ) 24 weeks post-treatment) of response guided therapy (RGT) with GS-9451 + GS-5885, with peginterferon alfa-2a (PEG) and ribavirin (RBV) in treatment-experienced subjects.
| Arm | Type | Description |
|---|---|---|
| LDV/SOF (Cohort 1) | EXPERIMENTAL | LDV/SOF FDC for 12 weeks |
| SOF+RBV (Cohort 1) | EXPERIMENTAL | SOF+RBV for 12 weeks |
| LDV/SOF (Cohort 2) | EXPERIMENTAL | Participants who are ineligible for or intolerant to RBV therapy will receive LDV/SOF FDC for 12 weeks. |
| LDV/SOF | EXPERIMENTAL | LDV/SOF FDC for 12 weeks |
| LDV/SOF 8 wk TN (Cohort 1, Group 1) | EXPERIMENTAL | LDV/SOF for 8 weeks (treatment-naive (TN)) |
| LDV/SOF+RBV 8 wk TN (Cohort 1, Group 2) | EXPERIMENTAL | LDV/SOF+RBV for 8 weeks (treatment-naive) |
| LDV/SOF 12 wk TN (Cohort 1, Group 3) | EXPERIMENTAL | LDV/SOF for 12 weeks (treatment-naive) |
| LDV/SOF+RBV 12 wk TN (Cohort 1, Group 4) | EXPERIMENTAL | LDV/SOF+RBV for 12 weeks (treatment-naive) |
| LDV/SOF+RBV 12 wk TE (Cohort 2) | EXPERIMENTAL | Treatment-experienced (TE) participants who completed treatment in Gilead sponsored study GS-US-334-0138 or in Cohort 1 of this study and did not achieve SVR12 will receive LDV/SOF+RBV for 12 weeks. |
| LDV/SOF 12 wk TE (Cohort 3, Group 1) | EXPERIMENTAL | LDV/SOF for 12 weeks (treatment-experienced) |
| LDV/SOF+RBV 12 wk TE (Cohort 3, Group 2) | EXPERIMENTAL | LDV/SOF+RBV for 12 weeks (treatment-experienced) |
| LDV/SOF Coinfected with HIV-1 | EXPERIMENTAL | Treatment-naive participants with genotype 1 HCV infection without cirrhosis and who are coinfected with HIV-1 will receive LDV/SOF FDC for 8 weeks. |
| LDV/SOF+RBV Retreatment | EXPERIMENTAL | Participants with genotype 1 or 3 HCV infection who failed to achieve SVR12 in Gilead Study GS-US-334-0119 will receive LDV/SOF FDC + RBV for 12 weeks. |
| LDV/SOF 12 Weeks | EXPERIMENTAL | LDV/SOF for 12 weeks |
| Retreatment Substudy | EXPERIMENTAL | LDV/SOF plus RBV for 24 weeks |
| LDV/SOF (treatment naive) | EXPERIMENTAL | Treatment-naive participants will receive LDV/SOF for 12 weeks. |
| LDV/SOF+RBV (treatment naive) | EXPERIMENTAL | Treatment-naive participants will receive LDV/SOF plus RBV for 12 weeks. |
| LDV/SOF (treatment experienced) | EXPERIMENTAL | Treatment-experienced participants will receive LDV/SOF for 12 weeks. |
| LDV/SOF+RBV (treatment experienced) | EXPERIMENTAL | Treatment-experienced participants will receive LDV/SOF plus RBV for 12 weeks. |
| LDV/SOF 8 Week | EXPERIMENTAL | Participants will receive LDV/SOF FDC for 8 weeks. |
| LDV/SOF+RBV 8 Week | EXPERIMENTAL | Participants will receive LDV/SOF FDC plus RBV for 8 weeks. |
| LDV/SOF 12 Week | EXPERIMENTAL | Participants will receive LDV/SOF FDC for 12 weeks. |
| LDV/SOF+RBV 12 Weeks | EXPERIMENTAL | Participants will receive LDV/SOF FDC plus RBV for 12 weeks. |
| LDV/SOF 24 Weeks | EXPERIMENTAL | Participants will receive LDV/SOF FDC for 24 weeks. |
| LDV/SOF+RBV 24 Weeks | EXPERIMENTAL | Participants will receive LDV/SOF FDC plus RBV for 24 weeks. |
| LDV/SOF FDC | OTHER | Ledipasvir/Sofosbuvir fixed dose combination (FDC) tablet (LDV 90 mg/SOF 400 mg) once daily |
| LDV/SOF for 8 weeks | EXPERIMENTAL | Treatment-naive participants with genotype 1 without cirrhosis will receive LDV/SOF for 8 weeks |
| LDV/SOF for 12 weeks | EXPERIMENTAL | Treatment-experienced participants with genotype 1 and treatment-naive or treatment-experienced participants with genotype 2 (Taiwan only), 4, 5 and 6 without cirrhosis will receive LDV/SOF for 12 weeks |
| LDV/SOF for 24 weeks | EXPERIMENTAL | Participants with compensated cirrhosis will receive LDV/SOF for 24 weeks |
| LDV/SOF+RBV | EXPERIMENTAL | LDV/SOF FDC plus RBV for 12 weeks |
| 12 to < 18 Years Old | EXPERIMENTAL | Participants between 12 to \< 18 years of age weighing ≥ 45 kg will receive LDV/SOF FDC (90/400 mg tablet or 4 x 22.5 mg/100 mg tablets or 8 x 11.25/50 mg granules based on swallowability assessment during screening). Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment. United Kingdom: * HCV genotypes (GT) 1, 4, 5, or 6 treatment-naive (TN) with or without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 treatment-experienced (TE) without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks * HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks United States/Australia/New Zealand: * HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks * HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks * HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks |
| 6 to < 12 Years Old | EXPERIMENTAL | Participants between 6 to \< 12 years of age weighing ≥ 17 kg and \< 45 kg will receive LDV/SOF FDC (45/200 mg as 2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules based on swallowability assessment during screening). Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment. United Kingdom: * HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks * HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks United States/Australia/New Zealand: * HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks * HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks * HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks |
| 3 to < 6 Years Old | EXPERIMENTAL | Participants between 3 to \< 6 years of age weighing ≥ 17 kg will receive LDV/SOF FDC (45/200 mg granules as 4 x 11.25/50 mg packets) and participants weighing \< 17 kg will receive LDV/SOF FDC (33.75/150 mg oral granules as 3 x 11.25/50 mg packets). Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment. United Kingdom: * HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks * HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks United States/Australia/New Zealand: * HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks * HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks * HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks * HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks |
| LDV/SOF 12 wk | EXPERIMENTAL | Participants will receive LDV/SOF FDC for 12 weeks. |
| LDV/SOF 24 wk | EXPERIMENTAL | Participants will receive LDV/SOF FDC for 24 weeks. |
| LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1) | EXPERIMENTAL | Participants who previously received ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) for ≥ 12 weeks without achieving sustained virologic response at 12 weeks following treatment (SVR12) will receive LDV/SOF+RBV for 24 weeks. |
| LDV/SOF+RBV 12 Weeks (Cohort 1 Group 2) | EXPERIMENTAL | Participants who previously received a sofosbuvir-based regimen without achieving SVR12 were initially enrolled to receive LDV/SOF+RBV for 12 weeks (excluding participants who previously received LDV/SOF+RBV for ≥ 12 weeks). Participants who did not achieve sustained virologic response at 12 weeks were then moved to Cohort 1 Group 1. |
| LDV/SOF 12 Weeks GT2 (Cohort 2 Group 1) | EXPERIMENTAL | Participants with genotype 2 (GT2) HCV infection will receive LDV/SOF FDC for 12 weeks. |
| LDV/SOF 8 Weeks GT2 (Cohort 2 Group 2) | EXPERIMENTAL | Participants with GT2 HCV infection will receive LDV/SOF FDC for 8 weeks. |
| LDV/SOF 12 Weeks GT1/GT2/GT4 (Cohort 3 Group 1) | EXPERIMENTAL | Participants with genotypes 1 (GT1), 2 (GT2), or 4 (GT4) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC for 12 weeks. |
| LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2) | EXPERIMENTAL | Participants with genotype 3 (GT3) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC plus RBV for 12 weeks. |
| SOF/VEL+VOX 6 Weeks GT1 (Cohort 4) | EXPERIMENTAL | Treatment-naive participants with GT1 HCV infection without cirrhosis will receive VOX only on Day 1 followed by sofosbuvir/velpatasvir (SOF/VEL) + voxilaprevir (VOX) for 6 weeks. |
| SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1) | EXPERIMENTAL | Treatment-naive participants with GT1 HCV infection without cirrhosis will receive SOF/VEL+VOX for 4 weeks. |
| SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2) | EXPERIMENTAL | Treatment-naive participants with GT1 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks. |
| SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3) | EXPERIMENTAL | Treatment-naive participants with GT3 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks. |
| SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4) | EXPERIMENTAL | Treatment-experienced participants with GT1 HCV infection with cirrhosis who were previously treated with pegylated interferon (Peg-IFN)+RBV will receive SOF/VEL+VOX for 6 weeks. |
| SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5) | EXPERIMENTAL | Treatment-experienced participants with GT3 HCV infection with cirrhosis who were previously treated with Peg-IFN+RBV will receive SOF/VEL+VOX for 6 weeks. |
| SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6) | EXPERIMENTAL | Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with non-structural protein (NS3/4A) protease inhibitor (PI) will receive SOF/VEL+VOX for 6 weeks. |
| SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7) | EXPERIMENTAL | Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with direct-acting antivirals (DAA) will receive SOF/VEL+VOX for 6 weeks. |
| SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8) | EXPERIMENTAL | Treatment-experienced participants with GT3 HCV infection with or without cirrhosis who were previously treated with DAA will receive SOF/VEL+VOX for 8 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive LDV/SOF placebo for 12 weeks. |
| Open-Label Treatment Phase | EXPERIMENTAL | Following Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks. |
| LDV/SOF+VDV | EXPERIMENTAL | Participants will receive LDV/SOF+VDV for 8 weeks. |
| LDV/SOF+VDV+RBV | EXPERIMENTAL | Participants will receive LDV/SOF+VDV+RBV for 8 weeks. |
| LDV/SOF+RBV 12 weeks (Group 1) | EXPERIMENTAL | Participants who failed a prior SOF+RBV ± pegylated interferon (Peg-IFN) regimen will receive LDV/SOF FDC plus RBV for 12 weeks. |
| LDV/SOF 24 weeks (Group 2) | EXPERIMENTAL | Participants who failed a prior LDV/SOF ± RBV regimen will receive LDV/SOF FDC for 24 weeks. |
| LDV/SOF+RBV 24 weeks (Group 3) | EXPERIMENTAL | Participants with advanced compensated or decompensated cirrhosis who failed a prior SOF+RBV regimen will receive LDV/SOF FDC plus RBV for 24 weeks. |
| LDV/SOF GT 1 or 4 | EXPERIMENTAL | Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks. |
| SOF+RBV 12 wks GT 2 | EXPERIMENTAL | Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks. |
| SOF+RBV 24 wks GT 3 | EXPERIMENTAL | Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks. |
| Genotype 4 | EXPERIMENTAL | LDV/SOF for up to 12 weeks in treatment-naive and treatment-experienced participants with genotype 4 hepatitis C virus (HCV) infection |
| Genotype 5 | EXPERIMENTAL | LDV/SOF for up to 12 weeks in treatment-naive and treatment-experienced participants with genotype 5 hepatitis C virus (HCV) infection |
| Cohort A, Group 1 (12 wk): CPT Class B (7-9) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class B (CPT score 7-9) |
| Cohort A, Group 1 (24 wk): CPT Class B (7-9) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class B (CPT score 7-9) |
| Cohort A, Group 2 (12 wk): CPT Class C (10-12) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class C (CPT score 10-12) |
| Cohort A, Group 2 (24 wk): CPT Class C (10-12) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class C (CPT score 10-12) |
| Cohort B, Group 3 (12 wk): F0-F3 Fibrosis | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with Fibrosis Stage F0-F3 |
| Cohort B, Group 3 (24 wk): F0-F3 Fibrosis | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with Fibrosis Stage F0-F3 |
| Cohort B, Group 4 (12 wk): CPT Class A (5-6) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with CPT Class A (CPT score 5-6) |
| Cohort B, Group 4 (24 wk): CPT Class A (5-6) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with CPT Class A (CPT score 5-6) |
| Cohort B, Group 5 (12 wk): CPT Class B (7-9) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class B (CPT score 7-9) |
| Cohort B, Group 5 (24 wk): CPT Class B (7-9) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class B (CPT score 7-9) |
| Cohort B, Group 6 (12 wk): CPT Class C (10-12) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class C (CPT score 10-12) |
| Cohort B, Group 6 (24 wk): CPT Class C (10-12) | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class C (CPT score 10-12) |
| Cohort B, Group 7 (12 wk): FCH | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with FCH |
| Cohort B, Group 7 (24 wk): FCH | EXPERIMENTAL | LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with FCH |
| LDV/SOF + GS-9669 250 mg | EXPERIMENTAL | Participants will receive LDV/SOF plus GS-9669 250 mg for 8 weeks. |
| LDV/SOF + GS-9669 500 mg | EXPERIMENTAL | Participants will receive LDV/SOF plus GS-9669 500 mg (2 x 250 mg) for 8 weeks. |
| LDV/SOF + RBV | EXPERIMENTAL | Placebo to match SOF/LDV FDC plus placebo to match RBV for 12 weeks, followed by LDV/SOF FDC plus RBV for 12 weeks. |
| Cohort 1,Group 1: LDV/SOF + RBV 12 wk (GT1 SOF retreatment) | EXPERIMENTAL | LDV/SOF + RBV for 12 weeks in participants with genotype 1 HCV infection and who failed to achieve sustained virologic response (SVR) in a previous Gilead sofosbuvir study |
| Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment) | EXPERIMENTAL | SOF + PEG + RBV for 12 weeks in participants with genotype 2 or 3 HCV infection and who failed to achieve SVR in a previous Gilead sofosbuvir study |
| Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, liver disease) | EXPERIMENTAL | LDV/SOF+RBV for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis |
| Cohort 2,Group 2: LDV/SOF+GS-9669 12wk (GT1 TE, liver disease) | EXPERIMENTAL | LDV/SOF + GS-9669 for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis |
| Cohort 2,Group 3: LDV/SOF 12 wk (GT3 TN) | EXPERIMENTAL | LDV/SOF for 12 weeks in treatment-naive participants with genotype 3 HCV infection |
| Cohort 2,Group 4: LDV/SOF+RBV 12 wk (GT3 TN) | EXPERIMENTAL | LDV/SOF + RBV for 12 weeks in treatment-naive participants with genotype 3 HCV infection |
| Cohort 2,Group 5: LDV/SOF 12 wk (GT6 TE/TN) | EXPERIMENTAL | LDV/SOF for 12 weeks in treatment-naive or treatment-experienced participants with genotype 6 HCV infection |
| Cohort 2,Group 6: LDV/SOF+RBV 12 wk (GT3 TE) | EXPERIMENTAL | LDV/SOF + RBV for 12 weeks in treatment-experienced participants with genotype 3 HCV infection |
| Cohort 3,Group 1: LDV/SOF 12 wk (GT1 cirrhotic CPT B) | EXPERIMENTAL | LDV/SOF for 12 weeks in participants with genotype 1 HCV infection and Child-Pugh Turcotte (CPT) B cirrhosis |
| Cohort 4,Group 1: SOF+VEL 25mg 8 wk (GT3 TN noncirrhotic) | EXPERIMENTAL | SOF+VEL (25 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection |
| Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic) | EXPERIMENTAL | SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection |
| Cohort 4,Group 3: SOF+VEL 100mg 8 wk (GT3 TN noncirrhotic) | EXPERIMENTAL | SOF+VEL (100 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection |
| Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic) | EXPERIMENTAL | SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection |
| Cohort 5,Group 1: LDV/SOF + RBV 24 wk (SOF retreatment) | EXPERIMENTAL | LDV/SOF+RBV for 24 weeks in participants with genotype 1, 2, 3, or 6 HCV infection and who failed to achieve SVR in a previous Gilead sofosbuvir study |
| Cohort 6,Group 1: LDV/SOF 12 wk (GT1, HBV coinfection) | EXPERIMENTAL | LDV/SOF for 12 weeks in participants with genotype 1 HCV and hepatitis B virus (HBV) coinfection |
| LDV/SOF 8 Weeks (TN) | EXPERIMENTAL | Treatment-naive (TN) participants will be randomized to receive LDV/SOF for 8 weeks. |
| LDV/SOF+RBV 8 Weeks (TN) | EXPERIMENTAL | Treatment-naive participants will be randomized to receive LDV/SOF plus RBV for 8 weeks. |
| LDV/SOF 12 Weeks (TN) | EXPERIMENTAL | Treatment-naive participants will be randomized to receive LDV/SOF for 12 weeks. |
| LDV/SOF 12 Weeks (TE) | EXPERIMENTAL | Treatment-experienced (TE) participants (had virologic failure following prior therapy with a protease-inhibitor \[PI\]+pegylated interferon \[PEG\]+RBV regimen) will be randomized to receive LDV/SOF for 12 weeks. |
| LDV/SOF+RBV 12 Weeks (TE) | EXPERIMENTAL | Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) will be randomized to receive LDV/SOF plus RBV for 12 weeks. |
| Arm 1 | ACTIVE_COMPARATOR | GS-5885, GS-9451, tegobuvir (GS-9190), and Copegus® for 24 weeks |
| Arm 2 | ACTIVE_COMPARATOR | GS-5885, GS-9451, tegobuvir (GS-9190), and a placebo matching ribavirin for 24 weeks |
| Arm 3 | ACTIVE_COMPARATOR | GS-5885, GS-9451, a placebo matching tegobuvir, and Copegus® for 24 weeks |
| Cohort 1 | ACTIVE_COMPARATOR | GS-5885 (3 mg), once daily or matching placebo, once daily |
| Cohort 2 | ACTIVE_COMPARATOR | GS-5885 (10 mg), once daily or matching placebo, once daily |
| Cohort 3 | ACTIVE_COMPARATOR | GS-5885 (30 mg), once daily or matching placebo, once daily |
| Cohort 4 | ACTIVE_COMPARATOR | GS-5885 ( up to 90 mg), once daily or matching placebo, once daily |
| Cohort 5 | ACTIVE_COMPARATOR | GS-5885 (up to 90 mg), once daily or matching placebo, once daily |
| Cohort 6 (optional) | ACTIVE_COMPARATOR | GS-5885 (up to 90 mg), once daily or matching placebo, once daily |
| Name | Type | Description |
|---|---|---|
| LDV/SOF | DRUG | 90/400 mg FDC tablet administered orally once daily |
| SOF | DRUG | 400 mg tablet administered orally once daily |
| RBV | DRUG | Capsules administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, \> 60 kg to ≤ 80 kg = 800 mg, and \> 80 kg = 1000 mg) |
| LDV/SOF FDC | DRUG | Ledipasvir/Sofosbuvir fixed dose combination (FDC) tablet (LDV 90 mg/SOF 400 mg) once daily |
| SOF/VEL | DRUG | 400/100 mg FDC tablet administered orally once daily |
| VOX | DRUG | 100 mg tablet administered orally once daily with food |
| Placebo | DRUG | Tablet administered orally once daily |
| VDV | DRUG | VDV 80 mg tablet administered orally once daily |
| GS-9669 | DRUG | GS-9669 tablet(s) administered orally once daily |
| Placebo to match LDV/SOF | DRUG | Placebo to match LDV/SOF administered orally once daily |
| Placebo to match RBV | DRUG | Placebo to match RBV administered orally in a divided daily dose |
| Peg-IFN | DRUG | pegylated interferon (Peg-IFN) 180 µg administered subcutaneously once weekly |
| VEL | DRUG | Velpatasvir (VEL) tablet(s) administered orally once daily |
| GS-5885 tablet | DRUG | GS-5885 tablet, 90 mg, QD |
| GS-9451 tablet | DRUG | GS-9451 tablet, 200 mg QD |
| tegobuvir capsule | DRUG | tegobuvir capsule, 30 mg BID |
| ribavirin tablet | DRUG | ribavirin tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID) |
| placebo matching ribavirin tablet | DRUG | placebo matching ribavirin tablet, BID |
| placebo matching tegobuvir capsule | DEVICE | placebo matching tegobuvir capsule, BID |
| GS-5885 | DRUG | Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD |
| GS-9451 | DRUG | Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD |
| tegobuvir | DRUG | tegobuvir 30 mg BID |
| placebo to match tegobuvir | DRUG | tegobuvir placebo BID |
| Ribavirin | DRUG | Ribavirin (Copegus®) BID (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) divided BID |
| peginterferon alfa-2a | BIOLOGICAL | (solution for injection) 180 µg/week |
| GS-9451 Placebo | DRUG | Placebo to match GS-9451 QD |
Key Inclusion Criteria: * Chronic genotype 2 HCV-infected males and non-pregnant/non-lactating females * Aged 20 years or older * Treatment naive or treatment experienced * At least 20 subjects will have Child-Pugh-A compensated cirrhosis. In Cohort 2, participants must be ineligible or intolerant ...
LDV/SOF is a fixed-dose combination antiviral therapy developed by Gilead Sciences for the treatment of hepatitis C virus infection. It is studied across several HCV populations, including acute hepatitis C, chronic genotype 4 HCV, chronic HCV infection, and chronic hepatitis C. LDV/SOF is a small molecule therapy given as a fixed-dose combination.
LDV/SOF is developed by Gilead Sciences, Inc., which trades under the ticker GILD. Gilead is the sponsor of the clinical trial program evaluating the fixed-dose combination across hepatitis C virus infection populations, including chronic HCV, genotype 4 HCV, and patients with end stage renal disease on dialysis.
LDV/SOF is in clinical development, with Phase 2 and Phase 3 trials conducted in hepatitis C virus infection. The program includes 13 completed trials with no active trials currently listed, and a total enrollment of 2,058 participants across the studied HCV populations.
Completed LDV/SOF trials include NCT03036839 in adults with chronic HCV on dialysis for end stage renal disease, NCT02868242 in pediatric participants undergoing cancer chemotherapy, NCT02738333 in chronic genotype 2 HCV, and NCT02613871 in adults with chronic HCV and HBV coinfection. All four listed trials are completed.
LDV/SOF is used for hepatitis C virus infection, including acute hepatitis C, chronic genotype 4 HCV, chronic HCV infection, chronic hepatitis C, and HCV infection. Its clinical program covers adults on dialysis for end stage renal disease, pediatric patients undergoing cancer chemotherapy, and adults with chronic HCV and HBV coinfection.