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Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 or 24 Weeks in Genotype 1 or 4 HCV Infected Adults With Sickle Cell Disease

Phase 2
Completed
Conditions
Hepatitis C Virus Infection
Interventions
Drug: LDV/SOF
Registration Number
NCT02301936
Lead Sponsor
Gilead Sciences
Brief Summary

The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) administered for 12 or 24 weeks in adults with genotype 1 or 4 hepatitis C virus (HCV) infection with sickle cell disease (SCD).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
Inclusion Criteria
  • Chronic genotype 1 or 4 infected patients with sickle cell disease
  • HCV RNA ≥ 1,000 IU/mL at screening
  • Cirrhosis determination by transient elastography
  • Screening laboratory values within defined thresholds
  • Use of two effective contraception methods if female of childbearing potential or sexually active male

Key

Exclusion Criteria
  • Pregnant or nursing female
  • Co-infection with HIV or hepatitis B virus (HBV)
  • Current or prior history of clinical hepatic decompensation
  • Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
  • History of clinically significant illness or any other medical disorder that may interfere with treatment, assessment or compliance with the protocol

Note: Other protocol defined inclusion/Exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LDV/SOF 12 weeksLDV/SOFTreatment-naive or treatment-experienced participants without cirrhosis will receive LDV/SOF for 12 weeks.
LDV/SOF 24 weeksLDV/SOFTreatment-experienced participants with cirrhosis will receive LDV/SOF for 24 weeks.
Primary Outcome Measures
NameTimeMethod
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 Permanently Discontinued Any Study Drug Due to an Adverse EventUp to 24 weeks
Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4)Posttreatment Week 4

SVR4 was defined as HCV RNA \< the LLOQ 4 weeks following the last dose of study drug.

Percentage of Participants With HCV RNA < LLOQ on TreatmentWeeks 1, 2, 4, 8,12, 16, 20, and 24
HCV RNA Change From BaselineUp to 24 weeks
Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Short Form (SF-36) Health Survey Scale- Physical Component ScoreWeeks 4,12, 24, Posttreatment Weeks 4 and 12

The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.

Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Short Form (SF-36) Health Survey Scale- Mental Component ScoreWeeks 4,12, 24, Posttreatment Weeks 4 and 12

The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.

Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)Weeks 4,12, 24, Posttreatment Weeks 4 and 12

The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.

Percentage of Participants With Virologic FailureUp to Posttreatment Week 12

Virologic failure was defined as

* On-treatment virologic failure

* HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment,

* \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse)

* Relapse

* HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement

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