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NCT01962441

SOF (Sovaldi®) +RBV for 16 or 24 Weeks and SOF+RBV+Peg-IFN for 12 Weeks in Adults With Genotype 2 or 3 Chronic HCV Infection

Completed Phase 3 Results posted Last updated 20 June 2017
What this trial tests

Phase 3 trial testing SOF in Hepatitis C in 601 participants. Completed in 7 July 2016.

Timeline
24 September 2013
Primary endpoint
7 January 2015
7 July 2016

Quick facts

Lead sponsorGilead Sciences
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment601
Start date24 September 2013
Primary completion7 January 2015
Estimated completion7 July 2016
Sites78 locations across New Zealand, United Kingdom, Canada, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Hepatitis C. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) Primary · 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.

GroupValue95% CI
SOF+RBV 16 Weeks71.9
SOF+RBV 24 Weeks85.4
SOF+RBV+Peg-IFN 12 Weeks92.9
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event Primary · Up to 24 weeks
GroupValue95% CI
SOF+RBV 16 Weeks1.5
SOF+RBV 24 Weeks1.5
SOF+RBV+Peg-IFN 12 Weeks1.5
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) Secondary · Posttreatment Weeks 4 and 24

SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.

SVR4
GroupValue95% CI
SOF+RBV 16 Weeks73.0
SOF+RBV 24 Weeks85.9
SOF+RBV+Peg-IFN 12 Weeks95.9
SVR24
GroupValue95% CI
SOF+RBV 16 Weeks71.9
SOF+RBV 24 Weeks84.4
SOF+RBV+Peg-IFN 12 Weeks93.4
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 Secondary · Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Week 1
GroupValue95% CI
SOF+RBV 16 Weeks14.8
SOF+RBV 24 Weeks20.1
SOF+RBV+Peg-IFN 12 Weeks25.9
Week 2
GroupValue95% CI
SOF+RBV 16 Weeks53.3
SOF+RBV 24 Weeks53.5
SOF+RBV+Peg-IFN 12 Weeks67.0
Week 4
GroupValue95% CI
SOF+RBV 16 Weeks86.6
SOF+RBV 24 Weeks91.9
SOF+RBV+Peg-IFN 12 Weeks97.4
Week 8
GroupValue95% CI
SOF+RBV 16 Weeks99.5
SOF+RBV 24 Weeks99.5
SOF+RBV+Peg-IFN 12 Weeks99.5
Week 12
GroupValue95% CI
SOF+RBV 16 Weeks100.0
SOF+RBV 24 Weeks98.5
SOF+RBV+Peg-IFN 12 Weeks100.0
Week 16
GroupValue95% CI
SOF+RBV 16 Weeks99.0
SOF+RBV 24 Weeks99.5
Week 20
GroupValue95% CI
SOF+RBV 24 Weeks99.5
Week 24
GroupValue95% CI
SOF+RBV 24 Weeks100.0
HCV RNA at Weeks 1, 2, 4, 8, and 12 Secondary · Weeks 1, 2, 4, 8, and 12
Week 1
GroupValue95% CI
SOF+RBV 16 Weeks2.13± 0.658
SOF+RBV 24 Weeks2.08± 0.749
SOF+RBV+Peg-IFN 12 Weeks1.81± 0.576
Week 2
GroupValue95% CI
SOF+RBV 16 Weeks1.44± 0.436
SOF+RBV 24 Weeks1.45± 0.487
SOF+RBV+Peg-IFN 12 Weeks1.32± 0.342
Week 4
GroupValue95% CI
SOF+RBV 16 Weeks1.19± 0.156
SOF+RBV 24 Weeks1.21± 0.287
SOF+RBV+Peg-IFN 12 Weeks1.16± 0.085
Week 8
GroupValue95% CI
SOF+RBV 16 Weeks1.15± 0.021
SOF+RBV 24 Weeks1.15± 0.100
SOF+RBV+Peg-IFN 12 Weeks1.15± 0.000
Week 12
GroupValue95% CI
SOF+RBV 16 Weeks1.15± 0.000
SOF+RBV 24 Weeks1.17± 0.318
SOF+RBV+Peg-IFN 12 Weeks1.15± 0.000
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12 Secondary · Baseline; Weeks 1, 2, 4, 8, and 12
Week 1
GroupValue95% CI
SOF+RBV 16 Weeks-4.18± 0.559
SOF+RBV 24 Weeks-4.15± 0.664
SOF+RBV+Peg-IFN 12 Weeks-4.46± 0.556
Week 2
GroupValue95% CI
SOF+RBV 16 Weeks-4.86± 0.661
SOF+RBV 24 Weeks-4.78± 0.714
SOF+RBV+Peg-IFN 12 Weeks-4.96± 0.661
Week 4
GroupValue95% CI
SOF+RBV 16 Weeks-5.11± 0.671
SOF+RBV 24 Weeks-5.02± 0.735
SOF+RBV+Peg-IFN 12 Weeks-5.12± 0.699
Week 8
GroupValue95% CI
SOF+RBV 16 Weeks-5.16± 0.684
SOF+RBV 24 Weeks-5.08± 0.708
SOF+RBV+Peg-IFN 12 Weeks-5.12± 0.691
Week 12
GroupValue95% CI
SOF+RBV 16 Weeks-5.15± 0.686
SOF+RBV 24 Weeks-5.05± 0.788
SOF+RBV+Peg-IFN 12 Weeks-5.12± 0.691
Percentage of Participants Experiencing On-Treatment Virologic Failure Secondary · Up to 24 weeks

On-treatment virologic failure was defined as: * 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)

GroupValue95% CI
SOF+RBV 16 Weeks0
SOF+RBV 24 Weeks1.5
SOF+RBV+Peg-IFN 12 Weeks0
Percentage of Participants Experiencing Viral Relapse Secondary · Up to Posttreatment Week 24

Viral relapse is defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement.

GroupValue95% CI
SOF+RBV 16 Weeks26.7
SOF+RBV 24 Weeks12.3
SOF+RBV+Peg-IFN 12 Weeks4.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 24 weeks plus 30 days (Randomized Period) Up to 12 additional weeks plus 30 days (Retreatment Period). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Randomized Period: SOF+RBV 16 Weeks
Serious: 8/196 (4%)
Deaths: 0/196
Randomized Period: SOF+RBV 24 Weeks
Serious: 10/199 (5%)
Deaths: 0/199
Randomized Period: SOF+RBV+Peg-IFN 12 Weeks
Serious: 12/197 (6%)
Deaths: 0/197
Retreatment Period: SOF+RBV+Peg-IFN 12 Weeks
Serious: 1/30 (3%)
Deaths: 0/30

Serious adverse events (31 terms)

ReactionSystemRandomized Period: SOF+RBV…Randomized Period: SOF+RBV…Randomized Period: SOF+RBV…Retreatment Period: SOF+RB…
Acute coronary syndromeCardiac disorders
Atrial fibrillationCardiac disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
PancreatitisGastrointestinal disorders
VomitingGastrointestinal disorders
Chest painGeneral disorders
CellulitisInfections and infestations
PneumoniaInfections and infestations
Respiratory tract infectionInfections and infestations
Subcutaneous abscessInfections and infestations
OverdoseInjury, poisoning and procedural complications
Snake biteInjury, poisoning and procedural complications
Haemoglobin decreasedInvestigations
ArthritisMusculoskeletal and connective tissue disorders
Flank painMusculoskeletal and connective tissue disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Adenocarcinoma of colonNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Loss of consciousnessNervous system disorders
SyncopeNervous system disorders
Alcohol abusePsychiatric disorders
Alcohol withdrawal syndromePsychiatric disorders
DepressionPsychiatric disorders
Other adverse events (49 terms — click to expand)

ReactionSystemRandomized Period: SOF+RBV…Randomized Period: SOF+RBV…Randomized Period: SOF+RBV…Retreatment Period: SOF+RB…
FatigueGeneral disorders
HeadacheNervous system disorders
InsomniaPsychiatric disorders
NauseaGastrointestinal disorders
Influenza like illnessGeneral disorders
RashSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
Dyspnoea exertionalRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
IrritabilityPsychiatric disorders
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
AnxietyPsychiatric disorders
Depressed moodPsychiatric disorders
DizzinessNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
Pruritus generalisedSkin and subcutaneous tissue disorders
Back painMusculoskeletal and connective tissue disorders
Sleep disorderPsychiatric disorders
NasopharyngitisInfections and infestations
AnaemiaBlood and lymphatic system disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
AstheniaGeneral disorders
Upper respiratory tract infectionInfections and infestations
Dizziness posturalNervous system disorders
DysgeusiaNervous system disorders
LethargyNervous system disorders
Memory impairmentNervous system disorders

Most-reported serious reactions: Acute coronary syndrome, Atrial fibrillation, Abdominal pain, Nausea, Pancreatitis, Vomiting, Chest pain, Cellulitis.

Data from ClinicalTrials.gov NCT01962441 adverse events section.

Sponsor's own description

This study will assess the efficacy, safety, and tolerability of 16 or 24 weeks of sofosbuvir (Sovaldi®; SOF) + ribavirin (RBV), and 12 weeks of SOF+RBV+ pegylated interferon (Peg-IFN) in treatment-naive and treatment-experienced adults with chronic genotype 3 hepatitis C virus (HCV) infection, and treatment-experienced adults with cirrhosis and chronic genotype 2 HCV infection.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. PHYLOSCANNER: Inferring Transmission from Within- and Between-Host Pathogen Genetic Diversity.
    Wymant C, Hall M, Ratmann O, Bonsall D, et al · · 2018 · cited 141× · PMID 29186559 · DOI 10.1093/molbev/msx304
  2. Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus.
    Ansari MA, Pedergnana V, L C Ip C, Magri A, et al · · 2017 · cited 121× · PMID 28394351 · DOI 10.1038/ng.3835
  3. Interferon lambda 4 impacts the genetic diversity of hepatitis C virus.
    Ansari MA, Aranday-Cortes E, Ip CL, da Silva Filipe A, et al · · 2019 · cited 33× · PMID 31478835 · DOI 10.7554/elife.42463
  4. Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure.
    Smith DA, Fernandez-Antunez C, Magri A, Bowden R, et al · · 2021 · cited 16× · PMID 34671027 · DOI 10.1038/s41467-021-25649-6
  5. Impact of Interferon Lambda 4 Genotype on Interferon-Stimulated Gene Expression During Direct-Acting Antiviral Therapy for Hepatitis C.
    Ramamurthy N, Marchi E, Ansari MA, Pedergnana V, et al · · 2018 · cited 16× · PMID 29534310 · DOI 10.1002/hep.29877
  6. Impact of virus subtype and host <i>IFNL4</i> genotype on large-scale RNA structure formation in the genome of hepatitis C virus.
    Simmonds P, Cuypers L, Irving WL, McLauchlan J, et al · · 2020 · cited 7× · PMID 32747607 · DOI 10.1261/rna.075465.120
  7. Genome-wide association and gene-virus interaction study of liver disease in hepatitis C virus-infected patients
    Quistrebert J, Chai H, Chen Y, Ramamurthy N, et al · · 2025 · DOI 10.1101/2025.10.12.25337816
  8. Interplay of host and viral genetic variations in modulating antibody responses to genotype 3a hepatitis C virus: Implications for vaccine design.
    Wang Z, Humphreys I, Quistrebert J, Chai H, et al · · 2025 · PMID 41076628 · DOI 10.1016/j.celrep.2025.116418

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing