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

Study Overview
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Brief Summary
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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).

Official Title
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An Open-Label Study of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 or 24 Weeks in Genotype 1 or 4 HCV Infected Subjects With Sickle Cell Disease

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: LDV/SOF


Participation Criteria
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Eligibility Criteria
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Key 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF 12 weeks<br>Treatment-naive or treatment-experienced participants without cirrhosis will receive LDV/SOF for 12 weeks. | Drug: LDV/SOF<br>* 90/400 mg fixed dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|
| Experimental: LDV/SOF 24 weeks<br>Treatment-experienced participants with cirrhosis will receive LDV/SOF for 24 weeks. | Drug: LDV/SOF<br>* 90/400 mg fixed dose combination (FDC) tablet administered orally once daily<br>* Other names: GS-5885/GS-7977;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < the LLOQ 4 weeks following the last dose of study drug. | Posttreatment Week 4 | 
| Percentage of Participants With HCV RNA < LLOQ on Treatment |  | Weeks 1, 2, 4, 8,12, 16, 20, and 24 | 
| HCV RNA Change From Baseline |  | Up to 24 weeks | 
| Percentage of Participants With Virologic Failure | 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 | Up to Posttreatment Week 12 | 
| Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Short Form (SF-36) Health Survey Scale- Physical Component Score | 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. | Weeks 4,12, 24, Posttreatment Weeks 4 and 12 | 
| Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Short Form (SF-36) Health Survey Scale- Mental Component Score | 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. | Weeks 4,12, 24, Posttreatment Weeks 4 and 12 | 
| Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) | 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. | Weeks 4,12, 24, Posttreatment Weeks 4 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Gilead, Hepatitis C