NCT01958281

Brief Summary

The primary objectives of this study are to evaluate the safety and efficacy of sofosbuvir (SOF) plus ribavirin (RBV) for 24 weeks and ledipasvir/sofosbuvir (LDV/SOF) for 12 weeks, and to evaluate the steady state pharmacokinetics (PK) of SOF and its metabolites and LDV in participants with genotype (GT) 1, 3, or 4 hepatitis C virus (HCV) infection who have chronic renal insufficiency (impaired kidney function).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Oct 2013

Typical duration for phase_2

Geographic Reach
3 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 6, 2013

Completed
1 day until next milestone

Study Start

First participant enrolled

October 7, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 9, 2013

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 18, 2017

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 19, 2017

Completed
10 months until next milestone

Results Posted

Study results publicly available

August 8, 2018

Completed
Last Updated

August 8, 2018

Status Verified

July 1, 2018

Enrollment Period

3.8 years

First QC Date

October 6, 2013

Results QC Date

July 13, 2018

Last Update Submit

July 13, 2018

Conditions

HCV Infection

Outcome Measures

Primary Outcomes (14)

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

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

    Posttreatment Week 12

  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events

    Up to 24 weeks plus 30 days

  • Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

    Treatment-emergent laboratory abnormalities were defined as values that increased by at least 1 toxicity grade from baseline at any time postbaseline up to the date of last dose of study drug plus 30 days.

    Up to 24 weeks plus 30 days

  • Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities

    Up to 24 weeks plus 30 days

  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities

    Up to 24 weeks plus 30 days

  • Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

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

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

  • PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

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

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

  • PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

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

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

  • PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Cmax is defined as the maximum concentration of drug.

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

  • PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Cmax is defined as the maximum concentration of drug.

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

  • PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Cmax is defined as the maximum concentration of drug.

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

  • PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

  • PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

  • PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Secondary Outcomes (21)

  • 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 Overall Virologic Failure

    Up to Posttreatment Week 24

  • PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

  • PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

  • +16 more secondary outcomes

Study Arms (3)

SOF 200 mg + RBV 200 mg (Cohort 1)

EXPERIMENTAL

Participants with genotype 1 or 3 HCV infection will receive SOF 200 mg (2 × 100 mg tablets) plus RBV once daily for 24 weeks.

Drug: SOFDrug: RBV

SOF 400 mg + RBV 200 mg (Cohort 2)

EXPERIMENTAL

Participants with genotype 1 or 3 HCV infection will receive SOF 400 mg (4 × 100 mg tablets or 1 × 400 mg tablet) plus RBV once daily for 24 weeks.

Drug: SOFDrug: RBV

LDV/SOF (Cohort 3)

EXPERIMENTAL

Participants with genotype 1 or 4 HCV infection will receive LDV/SOF once daily for 12 weeks.

Drug: LDV/SOF

Interventions

SOFDRUG

Tablet(s) administered orally once daily

Also known as: Sovaldi®, GS-7977
SOF 200 mg + RBV 200 mg (Cohort 1)SOF 400 mg + RBV 200 mg (Cohort 2)
RBVDRUG

200 mg tablet administered orally once daily

SOF 200 mg + RBV 200 mg (Cohort 1)SOF 400 mg + RBV 200 mg (Cohort 2)
LDV/SOFDRUG

90/400 mg fixed-dose combination (FDC) tablet administered orally once daily

Also known as: Harvoni®
LDV/SOF (Cohort 3)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Cohorts 1 and 2: chronic genotype 1 or 3 HCV infection
  • Cohort 3: chronic genotype 1 or 4 HCV infection
  • HCV RNA ≥ 10\^4 IU/mL at screening
  • Screening labs within defined thresholds
  • Cirrhosis determination at screening

You may not qualify if:

  • Females who are pregnant or nursing or males who have a pregnant partner
  • Prior null response to pegylated interferon (Peg-IFN)+RBV therapy (Cohorts 1 and 2) or for individuals with cirrhosis, prior treatment failure with IFN-based therapy not resulting from treatment intolerance (Cohort 3)
  • Current of prior history of hepatic decompensation
  • Infection with hepatitis B virus (HBV) or HIV
  • History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with individual's treatment and/or adherence to the protocol

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Unknown Facility

San Francisco, California, 94115, United States

Location

Unknown Facility

Miami, Florida, 33134, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Detroit, Michigan, 48202, United States

Location

Unknown Facility

Rochester, New York, 14642, United States

Location

Unknown Facility

San Antonio, Texas, 78215, United States

Location

Unknown Facility

Seattle, Washington, 98104, United States

Location

Unknown Facility

Grafton, Auckland, 1142, New Zealand

Location

Unknown Facility

Christchurch, 8011, New Zealand

Location

Unknown Facility

San Juan, 00927, Puerto Rico

Location

Related Publications (4)

  • Gane EJ, Robson RA, Bonacini M, Maliakkal B, Kirby B, Liu L, et al. Safety, Antiviral Efficacy, and Pharmacokinetics of Sofosbuvir in Patients With Severe Renal Impairment [Poster 966]. The 65th Annual meeting of the American Association for the Study of Liver Diseases: The Liver Meeting (AASLD); 2014 November 07-11; Boston, MA.

    BACKGROUND

  • Martin P, Gane E, Ortiz-Lasanta G, Liu L, Sajwani K, Kirby B, et al. Safety and Efficacy of Treatment With Daily Sofosbuvir 400 mg + Ribavirin 200 mg for 24 Weeks in Genotype 1 or 3 HCV-Infected Patients With Severe Renal Impairment [Poster 1128]. American Association for the Study of Liver Diseases (AASLD); 2015 November 13-17; San Francisco, CA.

    BACKGROUND

  • Lawitz E, Landis CS, Maliakkal BJ, Bonacini M, Ortiz-Lasanta G, Zhang J, et al. Safety and Efficacy of Treatment with Once- Daily Ledipasvir/Sofosbuvir (90/400 mg) for 12 Weeks in Genotype 1 HCV-Infected Patients with Severe Renal Impairment [Abstract 1587]. The Liver Meeting® 2017 - The 68th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2017 20-24 October; Washington, D. C.

    BACKGROUND

  • Lawitz E, Landis CS, Flamm SL, Bonacini M, Ortiz-Lasanta G, Huang J, Zhang J, Kirby BJ, De-Oertel S, Hyland RH, Osinusi AO, Brainard DM, Robson R, Maliakkal BJ, Gordon SC, Gane EJ. Sofosbuvir plus ribavirin and sofosbuvir plus ledipasvir in patients with genotype 1 or 3 hepatitis C virus and severe renal impairment: a multicentre, phase 2b, non-randomised, open-label study. Lancet Gastroenterol Hepatol. 2020 Oct;5(10):918-926. doi: 10.1016/S2468-1253(19)30417-0. Epub 2020 Jun 10.

    PMID: 32531259DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvirledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine MonophosphateUracil NucleotidesPyrimidine NucleotidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleotidesNucleic Acids, Nucleotides, and NucleosidesRibonucleotides

Results Point of Contact

Title
Gilead Clinical Study Information Center
Organization
Gilead Sciences
GileadClinicalTrials@gilead.com
1-833-445-3230 (GILEAD-0)

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 6, 2013

First Posted

October 9, 2013

Study Start

October 7, 2013

Primary Completion

July 18, 2017

Study Completion

October 19, 2017

Last Updated

August 8, 2018

Results First Posted

August 8, 2018

Record last verified: 2018-07

Locations

NZ(2)PR(1)US(7)