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LDV/SOF

Phase 3

Hepatitis C Virus Infection | Small molecule | Infectious Disease |Gilead Sciences, Inc.|Last Updated: Mar 6, 2020

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials13
Total Enrollment1,437
FDA Designations
No designations recorded
Clinical Trials (13)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02738333Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Participants With Chronic Genotype 2 HCV InfectionPHASE3 COMPLETED 239 — — Apr 12, 2016May 11, 2017Nov 16, 201837 Japan
NCT02613871Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Adults With Chronic HCV and HBV CoinfectionPHASE3 COMPLETED 111 — — Dec 22, 2015Nov 7, 2018Mar 6, 20208 Taiwan
NCT02487030Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination, With or Without Ribavirin, in Egyptian Adults With Chronic Genotype 4 HCV InfectionPHASE3 COMPLETED 255 — — Sep 7, 2015Feb 4, 2017Nov 16, 20184 Egypt
NCT02472886Safety and Efficacy of Ledipasvir/Sofosbuvir in Adults With Chronic HCV InfectionPHASE3 COMPLETED 153 — — Jun 17, 2015Jun 30, 2016Nov 16, 201820 Estonia, Russia
NCT03036839Ledipasvir/Sofosbuvir in Adults With Chronic Hepatitis C Virus (HCV) Infection Who Are on Dialysis for End Stage Renal DiseasePHASE2 COMPLETED 95 — — Jun 27, 2017Feb 14, 2019Mar 2, 202021 United States, Belgium +3
NCT02868242Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed Dose Combination in the Treatment of Hepatitis C Virus (HCV) Infection in Pediatric Participants Undergoing Cancer ChemotherapyPHASE2 COMPLETED 19 — — Aug 28, 2016Feb 3, 2019Mar 2, 20201 Egypt
NCT02350569Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation SettingPHASE2 COMPLETED 17 — — May 22, 2015Apr 22, 2016Nov 19, 20186 United States
NCT02413593Safety 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 InfectionPHASE2 COMPLETED 111 — — Apr 1, 2015Jan 1, 2016Nov 16, 201815 Canada
NCT02301936Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 or 24 Weeks in Genotype 1 or 4 HCV Infected Adults With Sickle Cell DiseasePHASE2 COMPLETED 10 — — Mar 2, 2015Apr 18, 2016Nov 19, 20181 United States
NCT02249182Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-InfectionPHASE2 COMPLETED 226 — — Nov 5, 2014Aug 24, 2018Mar 2, 202031 United States, Australia +2
NCT02251717Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination (FDC) for 12 or 24 Weeks in Kidney Transplant Recipients With Chronic HCV InfectionPHASE2 COMPLETED 114 — — Oct 14, 2014Jun 16, 2016Nov 19, 20185 Austria, France +2
NCT02219685Ledipasvir/Sofosbuvir Fixed-Dose Combination on Cerebral Metabolism and Neurocognition in Treatment-Naive and Treatment-Experienced Participants With Chronic Genotype 1 HCV InfectionPHASE2 COMPLETED 40 — — Aug 1, 2014Apr 1, 2016Nov 16, 20181 United States
NCT02226549Ledipasvir/Sofosbuvir Fixed-Dose Combination and Vedroprevir With or Without Ribavirin in Treatment-Experienced Participants With Chronic Genotype 1 HCV Infection and CirrhosisPHASE2 COMPLETED 47 — — Jul 1, 2014Feb 1, 2015Nov 16, 20181 United States
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Study Endpoints
Primary Endpoints
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Posttreatment Week 12

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Up to 12 weeks
Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug
First dose date up to 12 weeks
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Posttreatment Week 12

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.

Percentage of Participants Who Discontinued LDV/SOF Drug Due to an Adverse Event (AE)
12 weeks
Percentage of Participants Who Discontinued Study Drug Due to Any Adverse Event (AE)
Up to 12 weeks
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
First dose date up to Week 24
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event
Up to 4 weeks
For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF
Cohorts 1 and 2 (6 to < 18 years of age): predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10; Cohort 3 (3 to < 6 years of age): predose, 0.5, 2, 4, 8, and 12 hours postdose on Day 10

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase
Up to 24 weeks
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: NAA + NAAG
Baseline; Posttreatment Week 4

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.

Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Choline
Baseline; Posttreatment Week 4

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.

Change From Baseline in MRS Metabolic Ratio at 4 Weeks After Discontinuation of Therapy: Myoinositol
Baseline; Posttreatment Week 4

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.

Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Memory T Score
Baseline; Posttreatment Week 4

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.

Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Attention Scaled Score
Baseline; Posttreatment Week 4

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.

Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 1 Processing Speed
Baseline; Posttreatment Week 4

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.

Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Executive 2 Conceptual Shift and Initiation
Baseline; Posttreatment Week 4

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.

Change From Baseline in Neurocognitive Function at 4 Weeks After Discontinuation of Therapy: Motor
Baseline; Posttreatment Week 4

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.

Secondary Endpoints
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
Posttreatment Week 4
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
Posttreatment Week 24
Percentage of Participants With HCV RNA < LLOQ at Week 1
Week 1
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
LDV/SOF (Cohort 1)EXPERIMENTALLDV/SOF FDC for 12 weeks
SOF+RBV (Cohort 1)EXPERIMENTALSOF+RBV for 12 weeks
LDV/SOF (Cohort 2)EXPERIMENTALParticipants who are ineligible for or intolerant to RBV therapy will receive LDV/SOF FDC for 12 weeks.
LDV/SOFEXPERIMENTALLDV/SOF FDC for 12 weeks
LDV/SOF 8 wk TN (Cohort 1, Group 1)EXPERIMENTALLDV/SOF for 8 weeks (treatment-naive (TN))
LDV/SOF+RBV 8 wk TN (Cohort 1, Group 2)EXPERIMENTALLDV/SOF+RBV for 8 weeks (treatment-naive)
LDV/SOF 12 wk TN (Cohort 1, Group 3)EXPERIMENTALLDV/SOF for 12 weeks (treatment-naive)
LDV/SOF+RBV 12 wk TN (Cohort 1, Group 4)EXPERIMENTALLDV/SOF+RBV for 12 weeks (treatment-naive)
LDV/SOF+RBV 12 wk TE (Cohort 2)EXPERIMENTALTreatment-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)EXPERIMENTALLDV/SOF for 12 weeks (treatment-experienced)
LDV/SOF+RBV 12 wk TE (Cohort 3, Group 2)EXPERIMENTALLDV/SOF+RBV for 12 weeks (treatment-experienced)
LDV/SOF Coinfected with HIV-1EXPERIMENTALTreatment-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 RetreatmentEXPERIMENTALParticipants 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 for 8 weeksEXPERIMENTALTreatment-naive participants with genotype 1 without cirrhosis will receive LDV/SOF for 8 weeks
LDV/SOF for 12 weeksEXPERIMENTALTreatment-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 weeksEXPERIMENTALParticipants with compensated cirrhosis will receive LDV/SOF for 24 weeks
LDV/SOF+RBVEXPERIMENTALLDV/SOF FDC plus RBV for 12 weeks
LDV/SOF 12 weeksEXPERIMENTALTreatment-naive or treatment-experienced participants without cirrhosis will receive LDV/SOF for 12 weeks.
LDV/SOF 24 weeksEXPERIMENTALTreatment-experienced participants with cirrhosis will receive LDV/SOF for 24 weeks.
12 to < 18 Years OldEXPERIMENTALParticipants 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 OldEXPERIMENTALParticipants 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 OldEXPERIMENTALParticipants 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 wkEXPERIMENTALParticipants will receive LDV/SOF FDC for 12 weeks.
LDV/SOF 24 wkEXPERIMENTALParticipants will receive LDV/SOF FDC for 24 weeks.
PlaceboPLACEBO_COMPARATORParticipants will receive LDV/SOF placebo for 12 weeks.
Open-Label Treatment PhaseEXPERIMENTALFollowing Posttreatment Week 4, participants in the placebo group will be offered open-label treatment with LDV/SOF FDC for 12 weeks.
LDV/SOF+VDVEXPERIMENTALParticipants will receive LDV/SOF+VDV for 8 weeks.
LDV/SOF+VDV+RBVEXPERIMENTALParticipants will receive LDV/SOF+VDV+RBV for 8 weeks.
Interventions
NameTypeDescription
LDV/SOFDRUG90/400 mg FDC tablet administered orally once daily
SOFDRUG400 mg tablet administered orally once daily
RBVDRUGCapsules 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)
PlaceboDRUGTablet administered orally once daily
VDVDRUGVDV 80 mg tablet administered orally once daily
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Eligibility Criteria
Age Range20 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites37

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 ...

Countries:JapanTaiwanEgyptEstoniaRussiaUnited StatesBelgiumGermanyItalyCanadaAustraliaNew ZealandUnited KingdomAustriaFrance
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