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

• ClinicalTrials.gov Identifier: NCT02301936
• Recruitment Status: Completed
• First Posted: November 26, 2014
• Results First Posted: May 25, 2017
• Last Update Posted: November 19, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: November 24, 2014
• First Posted Date: November 26, 2014
• Results First Submitted Date: April 18, 2017
• Results First Posted Date: May 25, 2017
• Last Update Posted Date: November 19, 2018
• Actual Study Start Date: March 2, 2015
• Actual Primary Completion Date: April 18, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2017)

• Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: 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 Event [ Time Frame: Up to 24 weeks ]

Original Primary Outcome Measures (submitted: November 24, 2014)

• Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
  SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
• Incidence of any adverse events leading to permanent discontinuation of study drug [ Time Frame: Up to 12 weeks ]

Current Secondary Outcome Measures (submitted: April 18, 2017)

• Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: 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 Treatment [ Time Frame: Weeks 1, 2, 4, 8,12, 16, 20, and 24 ]
• HCV RNA Change From Baseline [ Time Frame: Up to 24 weeks ]
• Percentage of Participants With Virologic Failure [ Time Frame: Up 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
• Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Short Form (SF-36) Health Survey Scale- Physical Component Score [ Time Frame: Weeks 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 Score [ Time Frame: Weeks 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: November 24, 2014)

• Proportion of participants with sustained virologic response 4 weeks after discontinuation of therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
  SVR4 is defined as HCV RNA < the LLOQ 4 weeks following the last dose of study drug.
• Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 12 weeks ]
• HCV RNA change from baseline [ Time Frame: Up to 8 weeks ]
• Proportion of participants with virologic failure [ Time Frame: Up to Posttreatment Week 24 ]
  Virologic failure is 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
• Change from pretreatment assessment in health-related quality of life [ Time Frame: Up to Posttreatment Week 12 ]
  Changes in health-related quality of life will be assessed at Week 4, Week 12 (end of treatment or early termination), and Posttreatment Weeks 4 and 12.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 or 24 Weeks in Genotype 1 or 4 HCV Infected Adults With Sickle Cell Disease
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis C Virus Infection

Intervention

Drug: LDV/SOF

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

Other Names:

• Harvoni®
• GS-5885/GS-7977

Study Arms

• Experimental: LDV/SOF 12 weeks
  Treatment-naive or treatment-experienced participants without cirrhosis will receive LDV/SOF for 12 weeks.
  Intervention: Drug: LDV/SOF
• Experimental: LDV/SOF 24 weeks
  Treatment-experienced participants with cirrhosis will receive LDV/SOF for 24 weeks.
  Intervention: Drug: LDV/SOF

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 26, 2016): 10
• Original Estimated Enrollment (submitted: November 24, 2014): 25
• Actual Study Completion Date: April 18, 2016
• Actual Primary Completion Date: April 18, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02301936
• Other Study ID Numbers: GS-US-337-1405
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: http://www.gilead.com/research/disclosure-and-transparency

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: April 2017