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Study of Oral Treatments for Hepatitis C (PRIORITIZE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02786537
Recruitment Status : Completed
First Posted : June 1, 2016
Results First Posted : November 24, 2020
Last Update Posted : December 6, 2021
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Merck Sharp & Dohme LLC
AbbVie
Information provided by (Responsible Party):
University of Florida

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Hepatitis C
Interventions Drug: SOF/LDV (sofosbuvir/ledipasvir)
Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only)
Drug: EBR/GZR (elbasvir/grazoprevir)
Drug: Ribavirin
Enrollment 1275
Recruitment Details Participants were consented at 34 US centers Between June 2016 and March 2018. Patients' insurance was screened for inclusion of SOF/LDV on formulary (the HCV regimen not provided by the study). However, following randomization, participants who were unable to obtain SOF/LDV through insurance received 1 of 2 Direct Acting Antiviral (DAA) HCV Treatment regimens 1)EBR/GZR or 2)PrOD during Phase 1 and received EBR/GZR during Phase 2.
Pre-assignment Details This study initially (Phase 1) randomized subjects to receive 1 of 3 HCV DAA regimens (EBR/GZR +/- RBV, LDV/SOF +/- RBV, or PrOD +/-RBV). In phase 2 of this study, randomization to PrOD regimen was discontinued and newly enrolled subjects were randomized to either EBR/GZR +/- RBV or LDV/SOF +/- RBV. Efficacy data was analyzed via original 'randomization' and as subjects were 'actually treated (regimen actually received)' while safety analysis was evaluated by actual treatment received.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD/RBV(Phase 1 Only) PrOD (Phase 1 Only)
Hide Arm/Group Description

Patients received EBR/GZR (elbasvir/grazoprevir) (Zepatier™) orally once daily with RBV for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food and with RBV: Ribavirin (200 mg pill) 1-3 pills/day, once or twice daily. Total daily dosage ranged from 200 to 1200 mg.

Patients received EBR/GZR (elbasvir/grazoprevir) (Zepatier™) orally once daily (without RBV) for 12 to 16 weeks

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks. Duration of treatment according to HCV treatment provider.

Patients received SOF/LDV(sofosbuvir/ledipasvir) (Harvoni®) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV/sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) 1 tablet daily for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) RBV (200 mg pill): 1-3 pills, once or twice daily (dosing per discretion of HCV provider). Total daily dosage ranged from 200 to 1200 mg.

Patients received SOF/LDV (sofosbuvir/ledipasvir) (Harvoni®) orally once daily with or without food 12 to 24 weeks

SOF/LDV: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider)

PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir (Viekira) once or twice daily with a meal for 12 to 24 weeks + RBV (provider discretion). Randomization to PrOD discontinued January 2017.

ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks with food (treatment duration and use of ribavirin as per HCV provider)

Dasabuvir: 250 mg twice daily for 12 to 24 weeks with a meal RBV: Ribavirin 200 to 600 mg once or twice daily

Randomization to Prod discontinued January 2017 (defining end of Phase 1) PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks

ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration as per HCV provider)

Dasabuvir: 250 mg daily for 12 to 24 weeks

Period Title: As Randomized
Started 56 644 15 413 99 48
Completed 50 582 15 378 87 41
Not Completed 6 62 0 35 12 7
Reason Not Completed
Adverse Event             0             11             0             4             6             2
Lack of Efficacy             0             0             0             1             0             0
Withdrawal by Subject             1             2             0             1             1             0
Death             0             2             0             3             1             0
Non-compliance with study drug             1             11             0             1             0             1
Lost to treatment follow-up             4             32             0             24             4             4
Incarceration             0             1             0             0             0             0
Opiate Dependency Relapse             0             1             0             0             0             0
HCV drugs stolen from pt             0             1             0             0             0             0
Advised to stop after lapse in dosing             0             1             0             0             0             0
Subject lost insurance             0             0             0             1             0             0
Period Title: As Treated
Started [1] 56 664 15 394 99 47
Completed 50 602 15 359 87 40
Not Completed 6 62 0 35 12 7
Reason Not Completed
Adverse Event             0             11             0             4             6             2
Death             0             2             0             3             1             0
Lack of Efficacy             0             0             0             1             0             0
Lost to Follow-up             4             32             0             25             4             4
Non-compliance with study drug             1             11             0             1             0             1
Lost insurance             0             0             0             1             0             0
Withdrawal by Subject             1             2             0             0             1             0
Incarceration             0             1             0             0             0             0
Opiate dependency relapse             0             1             0             0             0             0
Drugs stolen from patient             0             1             0             0             0             0
Advised to stop tx after loss of meds             0             1             0             0             0             0
[1]
Numbers represent treatment regimen that study participant actually started (received).
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PROD With RBV (Phase 1 Only) PROD (Phase 1 Only) Total
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Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily with RBV for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir 50/100mg tablet) once daily with or without food with or without RBV for 12 to 16 weeks (with RBV)

Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily without RBV for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir 50/100mg tablet): 1 tablet once daily with or without food with or without RBV for 12 to 16 weeks (without RBV)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks with Ribavirin (RBV) (treatment duration and use of ribavirin is per discretion of HCV provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (per discretion of provider)

SOF/LDV: Sofosbuvir/Ledipasvir (400/90 mg tablet ) 1 tablet orally once daily for approximately 12 to 24 weeks

Phase 1 only - Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks +/- RBV (provider discretion)

ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider)

Dasabuvir: 250 mg daily for 12 to 24 weeks

Phase 1 only - Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks

ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks Dasabuvir: 250 mg daily for 12 to 24 weeks

Total of all reporting groups
Overall Number of Baseline Participants 56 644 15 413 99 48 1275
Hide Baseline Analysis Population Description
Study participants as randomized to HCV treatment
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 644 participants 15 participants 413 participants 99 participants 48 participants 1275 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
44
  78.6%
547
  84.9%
8
  53.3%
319
  77.2%
86
  86.9%
35
  72.9%
1039
  81.5%
>=65 years
12
  21.4%
97
  15.1%
7
  46.7%
94
  22.8%
13
  13.1%
13
  27.1%
236
  18.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 56 participants 644 participants 15 participants 413 participants 99 participants 48 participants 1275 participants
55.1  (11.0) 53.3  (12.2) 61.1  (6.6) 56.2  (11.1) 54.5  (11.3) 59.9  (10.1) 54.7  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 644 participants 15 participants 413 participants 99 participants 48 participants 1275 participants
Female
13
  23.2%
280
  43.5%
6
  40.0%
157
  38.0%
35
  35.4%
16
  33.3%
507
  39.8%
Male
43
  76.8%
364
  56.5%
9
  60.0%
256
  62.0%
64
  64.6%
32
  66.7%
768
  60.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 56 participants 644 participants 15 participants 413 participants 99 participants 48 participants 1275 participants
Hispanic or Latino
5
   8.9%
44
   6.8%
0
   0.0%
26
   6.3%
5
   5.1%
1
   2.1%
81
   6.4%
Not Hispanic or Latino
51
  91.1%
586
  91.0%
14
  93.3%
375
  90.8%
90
  90.9%
45
  93.8%
1161
  91.1%
Unknown or Not Reported
0
   0.0%
14
   2.2%
1
   6.7%
12
   2.9%
4
   4.0%
2
   4.2%
33
   2.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 56 participants 644 participants 15 participants 413 participants 99 participants 48 participants 1275 participants
56 644 15 413 99 48 1275
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  10^6 units IU/mL
Number Analyzed 56 participants 644 participants 15 participants 413 participants 99 participants 48 participants 1275 participants
4.9  (6.7) 3.1  (4.9) 5.9  (4.7) 3.5  (4.4) 3.5  (3.8) 3.7  (4.2) 3.4  (4.7)
1.Primary Outcome
Title Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV
Hide Description

SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation at discretion of provider).

mITT with imputation (missing=failure). Total number of subjects reflects participants from EBR/GZR with or without RBV and SOF/LDV with or without RBV randomized during Phase 1 and Phase 2.

Time Frame 12 weeks post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
mITT with imputation, Missing SVR data = Failure. Numbers represent participants according to arm randomized (Period 1). Population excludes participants who did not start any HCV treatment.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks

EBR/GZV (50/100mg) tablet: once daily with or without food 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Overall Number of Participants Analyzed 56 644 15 413
Measure Type: Count of Participants
Unit of Measure: Participants
40
  71.4%
516
  80.1%
14
  93.3%
335
  81.1%
2.Primary Outcome
Title Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
Hide Description

SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).

Number of subjects reflects participants who started EBR/GZR or SOF/LDV- based treatment (with or without RBV) during Phase 1 and 2.

Time Frame 12-24 weeks post HCV treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All mITT without imputation (missing data excluded). Includes only number of participants for whom SVR12 data is available and based on study drug as randomized (Period 1). Participants for whom SVR 12 is not available are excluded from this table.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received elbasvir/grazoprevir (EBR/GZR) tablet orally once daily with or without Ribavirin (RBV) for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks Ribavirin (RBV) (200 mg pill)- 1-3 pills orally once or twice daily (dosage at provider discretion)

Patients received elbasvir/grazoprevir (EBR/GZR) once daily for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (treatment duration per discretion of provider)

sofosbuvir/ledipasvir: 1 Sofosbuvir/Ledipasvir (400/90 mg) tablet once daily with or without food for approximately 12 to 24 weeks Ribavirin (200 mg pill): 200 to 600 mg once or twice daily (treatment duration and dosage of ribavirin as per discretion of HCV provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily for 12 to 24 weeks (treatment duration as per discretion of HCV treatment provider) SOF/LDV (400/90 MG TABLET): 1 tablet orally once daily for 12 to 24 weeks
Overall Number of Participants Analyzed 46 540 15 344
Measure Type: Count of Participants
Unit of Measure: Participants
40
  87.0%
516
  95.6%
14
  93.3%
335
  97.4%
3.Primary Outcome
Title Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation
Hide Description

SVR (Sustained Virologic Response) 12 will be defined as patients who have undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).

mITT with imputation (missing=failure). Total number of subjects reflects participants from Phase 1 only.

Time Frame 12 weeks post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
mITT with imputation, Missing SVR data =failure. Numbers represent participants according to arm randomized (period 1). Population excludes participants who did not start any HCV treatment.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks

EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV)

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider)

RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks

Overall Number of Participants Analyzed 13 134 6 105 99 48
Measure Type: Count of Participants
Unit of Measure: Participants
9
  69.2%
108
  80.6%
6
 100.0%
88
  83.8%
77
  77.8%
42
  87.5%
4.Primary Outcome
Title Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)
Hide Description

SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).

Number of subjects reflects participants randomized during Phase 1 only.

Time Frame 12 -24 weeks post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed based on HCV treatment as assigned by randomization.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD (Phase 1 Only)
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily with Ribavirin (RBV) for 12 to 16 weeks (provider discretion)

EBR/GZR: Elbasvir/grazoprevir (50/100mg) 1 tablet once daily with or without food with or without RBV for 12 to 16 weeks

Ribavirin at dosages ranging from 200mg to 600 mg daily (or twice daily) can be added to HCV DAA treatment regimen at discretion of HCV treatment provider

Patients received EBR/GZR (elbasvir/grazoprevir) tablet tablet once daily without RBV for 12 to 16 weeks (provider discretion)

EBR/GZR: 1 Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) tablet orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

RBV: At discretion of provider, 200 mg pill, 1-3 pills/day, 1-2 times/day (daily dosing ranging from 200mg to 1200 mg daily) added to HCV treatment regimen

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV (Sofosbuvir/Ledipasvir 400/90 mg tablet): 1 tablet daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

Patients received PrOD (ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily) for 12 to 24 weeks with Ribavirin (RBV) (use and dosage at provider discretion)

ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet ) 2 tablets daily for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider) Dasabuvir: 500 mg tablet once or twice daily (morning and evening)

RBV: At discretion of provider, 200 mg pill, 1-3 pills/day, 1-2 times/day (daily dosing ranging from 200mg to 1200 mg daily) added to HCV treatment regimen

Patients received ProD (ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily) for 12 to 24 weeks without Ribavirin (at provider discretion)

ombitasvir/paritaprevir/ritonavir (Phase 1 only): Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider)

Dasabuvir: 250 mg tablet twice daily for 12 to 24 weeks

Overall Number of Participants Analyzed 10 113 6 92 80 42
Measure Type: Count of Participants
Unit of Measure: Participants
9
  90.0%
108
  95.6%
6
 100.0%
88
  95.7%
77
  96.3%
42
 100.0%
5.Primary Outcome
Title Mean Change in Headache-PRO Scores -Phase 1
Hide Description Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement in symptom.
Time Frame Baseline to On-Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who completed a baseline and on-treatment PRO and as treated (Period 2) during Phase 1 only.
Arm/Group Title EBR/GZR With Ribavirin (RBV) EBR/GZR Regimen SOF/LDV With RBV SOF/LDV PrOD With RBV Regimen PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily withRBV (at discretion of provider) for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg - 1 tablet once daily with or without food for 12 to 16 weeks RBV: Ribavirin (200 mg pills) 1-3 pills/day, 1-2 times/day (Total dosage 200-1200 mg day)

Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg - 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

RBV (200 mg pill): 1-3 pills once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Overall Number of Participants Analyzed 9 84 5 61 62 28
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.0  (1.4) -0.8  (3.5) -0.7  (5.0) -0.5  (4.8) -0.2  (4.7) -2.2  (4.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF/LDV, PrOD
Comments PROD vs. SOF/LDV based regimens as reported in PRO (ALL PATIENTS WHO STARTED TREATMENT BY ARM AS TREATED), population limited to as randomization date of the last PrOD patient start date - RBV FREE REGIMENS
Type of Statistical Test Superiority
Comments Superiority test derived by comparing whether the 95% CI includes zero.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-3.6 to 0.3
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EBR/GZR Regimen, PrOD
Comments RBV free EBR/GZR regimen compared to PrOD in consideration that RBV usage was determined by provider and not study randomization.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-0.4 to 3.1
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method. CI for median derived from PROC QUANTREG.
6.Primary Outcome
Title Mean Change in Headache-EBR/GZR and SOF/LDV
Hide Description Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame Baseline to On-Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to participants who completed both baseline and end of treatment PRO
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)

Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Overall Number of Participants Analyzed 40 403 10 222
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.8  (3.1) -0.7  (4.4) 0.4  (6.2) -0.8  (5.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR, SOF/LDV
Comments Analysis based on RBV free EBR/GZR regimen vs SOF/LDV (all patients who started treatment by arm as treated)
Type of Statistical Test Superiority
Comments Superiority test completed by comparing whether the 95% CI includes zero.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.6 to 1.0
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.
7.Primary Outcome
Title Median Change in Headache -Phase 1
Hide Description Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame 12 weeks (Baseline and Average On-treatment Score)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients randomized up to last patient randomized to PrOD and participants who completed baseline and on-treatment survey.
Arm/Group Title EBR/GZR (Elbasvir/Grazoprevir) With RBV EBR/GZR (Elbasvir/Grazoprevir) SOF/LDV (Sofosbuvir/Ledipasvir) With RBV SOF/LDV (Sofosbuvir/Ledipasvir) PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) With RBV (Phase 1 Only) PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir)
Hide Arm/Group Description:

Patients received 1 EBR/GZR (elbasvir/grazoprevir) (Zepatier) tablet (50/100mg) once daily for 12 to 16 weeks (provider discretion) with Ribavirin (RBV)

EBR/GZR (elbasvir/grazoprevir): Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks

Ribavirin: 200 mg/tablet, 1-3/day, taken 1-2 times per day (dosage at discretion of provider).

Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (treatment duration per provider discretion)

EBR/GZR (elbasvir/grazoprevir): Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food for 12 to 16 weeks

Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) (Harvoni) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (duration and usage of RBV at discretion of provider).

SOF/LDV (sofosbuvir/ledipasvir): Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks

Ribavirin (RBV): 200 mg/tablet(capsule), 1-3 pills/day, 1-2 times/day.

Patients received 1 SOF/LDV (sofosbuvir/ledipasvir) tablet (400/90 mg) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV (sofosbuvir/ledipasvir): Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration at discretion of HCV provider)

Patients received Pr0D (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) orally daily with food for 12 to 24 weeks with RBV (Ribavirin).

Ombitasvir/Paritaprevir/Ritonavir (12.5/75/50 mg/tablet) -2 tablets once daily with food for 12 to 24 weeks and 1 dasabuvir tablet (250 mg) twice daily with food for 12 to 24 weeks.

RBV (200 mg/pill) 1-3 pills/day, 1-2 times/day (use and dosage at provider discretion). Total daily RBV dosage ranged from 200 to 1200 mg.

Patients received 2 ombitasvir/paritaprevir/ritonavir tablets (12.5/75/50 mg) once daily and 1 dasabuvir (250 mg) tablet twice daily with food for 12 to 24 weeks without Ribavirin (as per provider instructions)

PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only): Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) (2 tablets taken orally) and Dasabuvir (250 mg tablet) (1 tablet twice daily) with food for 12 to 24 weeks (treatment duration as per HCV provider)

Overall Number of Participants Analyzed 9 84 5 61 62 28
Median (Full Range)
Unit of Measure: units on a scale
0.0
(-2.0 to 2.0)
0.0
(-12.5 to 9.5)
-2.0
(-6.5 to 5.0)
-1.0
(-12.8 to 13.5)
0.0
(-17.0 to 8.5)
-1.0
(-15.0 to 3.0)
8.Primary Outcome
Title Median Change in Headache-Phase 2
Hide Description Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of median change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD
Time Frame Baseline -on Treatment (12-16 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients randomized to EBR/GZR regimen or SOF/LDV regimen and participants who completed both baseline and on treatment survey.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks.

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration per investigator's discretion)

EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without RBV

SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Overall Number of Participants Analyzed 40 403 10 222
Median (Full Range)
Unit of Measure: units on a scale
-1.0
(-7.0 to 6.0)
0.0
(-20.0 to 14.0)
0.5
(-9.5 to 11.5)
-0.5
(-20.0 to 14.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR, SOF/LDV
Comments Analysis of EBR/GZR vs. SOF/LDV irrespective of RBV usage in consideration that RBV usage was determined by provider and not study randomization.
Type of Statistical Test Superiority
Comments Superiority test comparison based on whether the 95% CI includes zero
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
0.0 to 1.0
Estimation Comments The comparisons between regimens can be viewed as superiority test, by comparing whether the 95% CI includes zero
9.Primary Outcome
Title Mean Change in Nausea/Vomiting PRO Score -Phase 1
Hide Description

Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.

The estimates of mean change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes. The model expressed mean score as a function of DAA regimen, cirrhosis status, HCV genotype, sex, age, race, and previous treatment status.

Time Frame Baseline to On-Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is limited to patients who completed at least one baseline and one end of treatment PRO survey during Phase 1 (end date corresponds to last PrOD patient start date)
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)

Patients received EBR/GZR (elbasvir/grazoprevir ) once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Overall Number of Participants Analyzed 8 79 5 58 59 25
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.3  (5.0) -1.4  (8.8) -3.9  (4.0) -0.7  (10.7) 2.5  (8.6) 0.7  (12.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF/LDV, PrOD
Comments Analysis based on RBV free SOF/LDV vs. PrOD in consideration that RBV usage was determined by provider and not study randomization and limited RBV sample size.
Type of Statistical Test Superiority
Comments Superiority test comparison based on whether the 95% CI includes zero
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-4.2 to 7.0
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SOF/LDV, PrOD
Comments RBV free PrOD vs. SOF/LDV regimens (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date)
Type of Statistical Test Superiority
Comments Superiority test comparison based on whether the 95% CI includes zero.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-4.2 to 7.0
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.
10.Primary Outcome
Title Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF
Hide Description

Participants completed the Patient Reported Outcomes surveys (PROs) 'PROMIS Nausea/Vomiting -4 Short Form' at baseline and during treatment. Raw scores are converted to standardized T-scores with a range of 45.0-80.1. Higher scores indicate worse nausea/vomiting.

Results presented as mean difference from baseline to average of on Treatment Scores (highest/worst) score during treatment.

A negative (-) PROMIS change score is suggestive of symptom improvement or lack of drug side effect. Estimates of mean change were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.

Time Frame Baseline and Average On-Treatment Score
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with Baseline PROMIS Nausea/vomiting score who started treatment by arm as treated and completed baseline and on-treatment survey.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage 200 mg- 1200 mg.

Patients received 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Overall Number of Participants Analyzed 37 381 9 202
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.3  (8.3) -0.6  (8.7) -1.6  (4.7) -0.4  (9.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR, SOF/LDV
Comments RBV free EBR/GZR vs. SOF/LDV (all patients who started treatment by arm as treated)
Type of Statistical Test Superiority
Comments Superiority test comparison based on whether the 95% CI includes zero
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.6 to 1.3
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.
11.Primary Outcome
Title Median Change in Nausea PRO Score -Phase 1
Hide Description

Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.

The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.

Time Frame Baseline to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who completed baseline and on treatment Nausea short form during Phase 1 (up to last PrOD randomized) as treated.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration as per discretion of HCV provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Overall Number of Participants Analyzed 8 79 5 58 59 25
Median (Full Range)
Unit of Measure: units on a scale
0.4
(-6.5 to 10.0)
0.0
(-22.2 to 20.8)
-6.1
(-8.0 to 0.9)
0.0
(-21.6 to 23.7)
0.0
(-19.2 to 22.2)
0.0
(-25.2 to 31.7)
12.Primary Outcome
Title Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV
Hide Description

Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for change represent improvement.

The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes.

Time Frame Baseline- On Treatment (up to 16 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)

Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks

EBR/GZV (50/100mg) tablet: once daily with or without food 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: RBV(Ribavirin) (200mg tablet): 1 - 3 tablets,1-2 times per day (dosage and duration per discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Overall Number of Participants Analyzed 37 381 9 202
Median (Full Range)
Unit of Measure: score on a scale
0.0
(-21.0 to 18.3)
0.0
(-29.2 to 23.3)
0.0
(-8.0 to 7.3)
0.0
(-26.1 to 24.9)
13.Primary Outcome
Title Mean Change in Fatigue PRO Score -Phase 1
Hide Description Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame Baseline to On-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who completed baseline and at least one on-treatment Fatigue PRO survey during phase 1 as treated.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider). Total daily dosage ranged from 200 to 1200 mg daily.

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Patients received PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV).

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

RBV (200 mg tablet): 1-3 tablets, 1-2 times per day, daily for 12 to 24 weeks (dosage and duration at discretion of provider)

Patients received PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV).

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Overall Number of Participants Analyzed 9 78 5 59 59 27
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.5  (7.7) -1.2  (9.2) -7.2  (10.2) -2.0  (7.9) -1.9  (11.3) -3.0  (7.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR, PrOD
Comments RBV free EBR/GZR vs. PrOD regimens as reported in PRO (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date). Analysis limited to RBV free regimen in consideration RBV usage determined by provider and not study randomization.
Type of Statistical Test Superiority
Comments Superiority test based on whether the 95% CI includes zero
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-1.9 to 5.5
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SOF/LDV, PrOD
Comments RBV free SOF/LDV vs. PrOD regimens as reported in PRO (all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date)
Type of Statistical Test Superiority
Comments Superiority test based on whether the 95% CI includes zero
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-4.6 to 2.7
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.
14.Primary Outcome
Title Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV
Hide Description Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame Baseline and Average On-Treatment Score
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with Baseline PROMIS Fatigue score who started treatment by arm as treated (Period 2)
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion)

Ribavirin (RBV) 200 mg tablet: 1 - 3 tablets,1-2 times per day, daily for 12 to 16 weeks (dosage and duration per discretion of provider).

Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion)

Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food, daily for 12 - 24 weeks (use of RBV and dosage at discretion of provider)

Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Overall Number of Participants Analyzed 38 398 10 213
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.0  (7.7) -2.1  (9.1) -3.7  (8.3) -2.2  (8.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR, SOF/LDV
Comments Analysis limited to RBV free regimens in consideration that RBV usage determined by provider and not study randomization. All patients who started treatment by arm as treated.
Type of Statistical Test Superiority
Comments Superiority test comparison based on presence of zero in 95% CI.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-1.4 to 1.6
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method
15.Primary Outcome
Title Median Change in Fatigue -Phase 1
Hide Description Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame Baseline to End of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is limited to patients who completed baseline and on-treatment fatigue PRO during Phase 1 (last PrOD patient started). Safety profiles of the evaluated regimens in PRIORITIZE are by actual treatment received.
Arm/Group Title EBR/GZR With RBV EBR/GZR Regimen SOF/LDV With RBV SOF/LDV PrOD Regimen With RBV PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider). Total daily dosage ranged from 200 to 1200 mg daily.

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks with or without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV).

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Overall Number of Participants Analyzed 9 78 5 59 59 27
Median (Full Range)
Unit of Measure: units on a scale
2.2
(-9.2 to 15.0)
-0.9
(-31.0 to 24.2)
-10.2
(-20.0 to 7.2)
-3.4
(-21.1 to 16.4)
-0.2
(-33.4 to 17.8)
-4.1
(-17.5 to 16.6)
16.Primary Outcome
Title Median Change in Fatigue-Phase 2
Hide Description Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.
Time Frame Baseline-On Treatment (up to 16 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to Period 2 -as treated, participants who completed baseline and on-treatment surveys.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received elbasvir/grazoprevir (EBR/GZR) tablet orally once daily with or without Ribavirin (RBV) for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks Ribavirin (RBV) (200 mg tablet)- 1-3 tablets orally, once or twice daily (dosage at provider discretion). Total daily dosage 200 -1200 mg.

Patients received elbasvir/grazoprevir (EBR/GZR) once daily for 12 to 16 weeks EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (treatment duration per discretion of provider)

sofosbuvir/ledipasvir: 1 Sofosbuvir/Ledipasvir (400/90 mg) tablet once daily with or without food for approximately 12 to 24 weeks Ribavirin (200 mg tablet): 1-3 tablets, once or twice daily (treatment duration and dosage of ribavirin as per discretion of HCV provider).

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily for 12 to 24 weeks (treatment duration as per discretion of HCV treatment provider) SOF/LDV (400/90 MG TABLET): 1 tablet orally once daily for 12 to 24 weeks
Overall Number of Participants Analyzed 38 398 10 213
Median (Full Range)
Unit of Measure: units on a scale
-1.3
(-19.1 to 15.0)
-1.2
(-31.6 to 24.2)
-2.4
(-20.0 to 7.2)
-1.4
(-39.0 to 20.7)
17.Primary Outcome
Title Mean Change in HCV- PRO- Phase 1
Hide Description

HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'overall functioning and well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.

Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.

Time Frame Baseline to End of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who completed baseline and at least one on treatment Fatigue Short form. Evaluation is based on actual HCV regimen received.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dose ranging from 200 mg to 1200 mg.

Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

RBV (200 mg tablet): 1-3 tablets, once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider).

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Overall Number of Participants Analyzed 9 84 5 61 61 29
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.9  (12.4) 5.6  (14.0) 2.5  (7.1) 6.9  (16.9) 3.2  (22.8) 9.9  (12.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR, PrOD
Comments Analysis based on RBV free regimens -all patients who started treatment by arm as treated, population is limited to as randomization date of the last PrOD patient start date.
Type of Statistical Test Superiority
Comments Superiority test determined by comparing presence of zero in CI.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.3
Confidence Interval (2-Sided) 95%
-9.9 to 1.3
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SOF/LDV, PrOD
Comments RBV free regimens as reported in PRO (all patients who started treatment by arm as treated, population limited to as randomization date of the last PrOD patient start date)
Type of Statistical Test Superiority
Comments Superiority comparison by viewing presence of zero in CI.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-3.4 to 9.4
Estimation Comments [Not Specified]
18.Primary Outcome
Title Median Change in HCV-PRO (Overall Well Being) -Phase 1
Hide Description

HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'Overall Functioning and Well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.

Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.

Time Frame Baseline to End of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who completed baseline and at least one survey while on treatment up to end of treatment. Evaluation was based on actual regimen received versus regimen to which patient was randomized.
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Hide Arm/Group Description:

Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg tablet): 1 to 3 tablets, once or twice daily (dosage and duration per discretion of provider)

Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration and use of ribavirin is per discretion of HCV provider)

RBV (Ribavirin) 200mg tablet: 1 to 3 tablets, once or twice daily at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV 400/90 mg tablet: 1 tablet once daily for approximately 12 to 24 weeks (treatment duration as HCV provider discretion)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV). Treatment duration and use of ribavirin as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranging from 200 - 1200 mg.

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV). Treatment duration as per HCV provider

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks (dosage at discretion of provider)

Overall Number of Participants Analyzed 9 84 5 61 61 29
Median (Full Range)
Unit of Measure: score on a scale
0.0
(-21.9 to 16.4)
4.3
(-32.8 to 43.0)
4.7
(-9.4 to 7.8)
4.7
(-39.8 to 47.7)
3.1
(-50.0 to 71.9)
8.6
(-19.7 to 31.3)
19.Primary Outcome
Title Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2
Hide Description

HCV-PRO, a survey designed to assess functional status of patients with HCV and measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.

Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered. End of Treatment -Baseline were used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2.

Time Frame End of Treatment - Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with completed Baseline and End of Treatment HCV-PRO survey who started treatment by arm as treated (Period 2)
Arm/Group Title EBR/GZR With RBV EBR/GZR SOF/LDV With RBV SOF/LDV
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (at discretion of provider) for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dose ranging from 200 mg to 1200 mg.

Patients received EBR/GZR (elbasvir/grazoprevir) once daily without RBV (at discretion of provider) for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet orally once daily with or without food for 12 to 16 weeks (duration per provider discretion)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Overall Number of Participants Analyzed 40 413 10 226
Mean (Standard Deviation)
Unit of Measure: score on a scale
3.2  (18.6) 6.1  (15.7) 6.3  (10.7) 6.8  (18.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR, SOF/LDV
Comments Analysis based on RBV free regimens in consideration that RBV usage was determined by provider and not study randomization. Population includes patients who started treatment by arm as treated.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-3.6 to 2.1
Estimation Comments CI for mean derived from PROC TTEST, difference in mean and its 95%CI was calculated by Satterthwaite method.
20.Primary Outcome
Title 16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs
Hide Description

Efficacy of Hepatitis C Virus (HCV) Treatment with Zepatier (Elbasvir/Grazobevir) with Ribavirin (RBV) for 16 weeks when used in Genotype 1a patients with Baseline RASs (NS5a Resistance Associated Substitutions or RAPs -Resistance Associated Polymorphisms).

Efficacy defined as HCV RNA undetectable 12 weeks post treatment. Table excludes Genotype 1b patients.

Time Frame 12 weeks post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All Genotype 1a patients who started treatment by arm randomized (Elbasvir/Grazobevir) with Baseline RAS at any location (28, 30, 31, or 93)
Arm/Group Title EBR/GZR With RBV-16 Weeks
Hide Arm/Group Description:

Subjects received EBR/GZR (elbasvir/grazoprevir) once daily with Ribavirin (RBV) for 16 weeks (as per provider discretion)

EBR/GZR: Elbasvir/grazoprevir (50/100mg tablet) 1 tablet once daily with or without food

RBV (200 mg tablet): 1-3 tablets once or twice daily for 16 weeks (dosage and duration at discretion of provider). Total dosage ranging from 200 mg to 1200 mg daily.

Overall Number of Participants Analyzed 38
Measure Type: Count of Participants
Unit of Measure: Participants
34
  89.5%
21.Secondary Outcome
Title Treatment Non-Adherence Probability Estimates
Hide Description The Voils Medication Adherence Survey (VMAS) was used to evaluate medication adherence during HCV treatment. Participants responded to three questions about the extent of adherence during the past seven days of treatment (during early and late on-treatment occasions). Participants responded using a five-point ordinal scale of missed dosing from 1 (none of the time) to 5 (all of the time). On each occasion participants were coded as being "Non-adherent" if any response was > 1, otherwise they were coded as "Adherent". Probability estimates of percentage of patients reporting non-adherence were calculated per HCV treatment (Direct Acting Antiviral-DAA) regimen: 1)EBR/GZV (elbasvir/grazoprevir, 2)SOF/LDV (sofosbuvir/ledipasvir), 3)PrOD
Time Frame 12-16 weeks of HCV treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is limited to participants to patients who started treatment prior to January 2017 (last day patient started on PrOD treatment)
Arm/Group Title EBR/GZR SOF/LDV PrOD
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with or without RBV for 12 to 16 weeks (provider discretion)

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranging from 200-1200 mg.

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with or without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with or without Ribavirin

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)

Overall Number of Participants Analyzed 151 108 146
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
23
(17 to 29)
19
(10 to 27)
26
(19 to 33)
22.Secondary Outcome
Title Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation
Hide Description Change in HCV-associated symptoms was calculated as the mean differences of mean scores from multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS)-- Fatigue, nausea, belly pain, sleep disturbance, and diarrhea) and functional status (well-being) when comparing baseline to early post-treatment and late post treatment surveys. Mean change scores were calculated by comparing baseline to early post-treatment (1 yr) and late post-treatment (approximately 3 years) surveys. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.Negative numbers suggest better symptoms (improvement in HCV-associated symptoms). PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.HCV-PRO positive estimates suggest baseline functional well-being improvement.
Time Frame 1 year post treatment discontinuation (Early post-tx)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis includes all patients who started treatment on either EBR/GZR or SOF/LDV regimen and is limited to patients who completed surveys. Analysis does not decipher between RBV usage given RBV usage was based on HCV provider selection and not study randomization
Arm/Group Title EBR/GZR Regimen SOF/LDV Regimen
Hide Arm/Group Description:

Patients received elbasvir/grazoprevir tablet tablet once daily with or without RBV (at discretion of provider) for 12 to 16 weeks (provider discretion)

elbasvir/grazoprevir: Elbasvir/grazoprevir (50/100mg) tablet once daily with food and with RBV: Ribavirin (200 mg/pill) 1-3 pills/day, 1-2 times/day. Total daily dosage ranged from 200 to 1200 mg.

Patients received 1 tablet SOF/LDV(sofosbuvir/ledipasvir) orally once daily with or without ribavirin (RBV) (per discretion of provider) with or without food 12 to 24 weeks

SOF/LDV/sofosbuvir/ledipasvir: Sofosbuvir/Ledipasvir (400/90 mg) for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) RBV: Ribavirin (200mg pill) 1-3 pills, once or twice/day -dosage at discretion of provider. Total daily dosage ranged from 200 to 1200 mg.

Overall Number of Participants Analyzed 507 286
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Nausea Number Analyzed 505 participants 285 participants
0.00
(-2.34 to 2.35)
-4.99
(-8.16 to -1.81)
Belly Pain Number Analyzed 503 participants 283 participants
-0.82
(-3.52 to 1.87)
-6.47
(-10.09 to -2.84)
Diarrhea Number Analyzed 504 participants 282 participants
-1.12
(-3.46 to 1.22)
-5.77
(-8.91 to -2.64)
Fatigue Number Analyzed 506 participants 285 participants
-2.08
(-4.74 to 0.58)
-7.59
(-11.17 to -4.01)
Sleep Disturbance Number Analyzed 505 participants 283 participants
0.65
(-0.70 to 2.00)
-1.72
(-3.81 to 0.37)
Cognitive Impairment Number Analyzed 507 participants 282 participants
-0.54
(-2.43 to 1.35)
-4.48
(-7.12 to -1.83)
HCV-PRO Number Analyzed 507 participants 286 participants
8.02
(3.94 to 12.11)
9.90
(4.27 to 15.52)
23.Secondary Outcome
Title Post-treatment Progression/Regression of Liver Disease-Fib-4
Hide Description Mean change (delta) in FIB-4, an indirect non-invasive measure of liver fibrosis, calculated as baseline median -long term follow up median, following SVR after any of the study treatment regimens. Change in FIB-4 where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change. FIB-4 = age (years) * AST(IU/L)/Platelets (10^3/L) * ALT^.5(IU/L). In general, Score of 0-1.29 is low risk for advanced fibrosis, 1.30-1.67: intermediate risk for advanced liver fibrosis, >2.67: high risk for advanced fibrosis.
Time Frame Baseline to up to 3 years post treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
Population analyzed limited to cirrhotic patients who had two separate FIB-4 values collected as part of standard care and achieved SVR (defined as undetectable HCV 24 weeks post treatment). Given pragmatic trial design, availability of fibrosis markers is limited thereby restricting analysis (substantially limited sample size) to difference in fibrosis markers following SVR with any HCV treatment used in study.
Arm/Group Title EBR/GZR, SOF/LDV or PrOD Based HCV Treatment
Hide Arm/Group Description:

Elbasvir/grazoprevir (EBR/GZR): (50/100mg) tablet once daily with food for 12 to 16 weeks with or without RBV (Ribavirin usage as per provider discretion).

Sofosbuvir/ledipasvir (SOF/LDV)/ (400/90 mg) 1 tablet once daily for approximately 12 to 24 weeks (treatment duration is per discretion of HCV provider) with or without RBV (RBV usage as per provider discretion):

PrOD: Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks + RBV (provider discretion)

ombitasvir/paritaprevir/ritonavir (Phase 1 only): (Phase 1 only) Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg) for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider)

Dasabuvir: 250 mg daily for 12 to 24 weeks RBV: Ribavirin 200 to 600 mg once or twice daily RBV (Ribavirin)- 200mg pill, 1-3 pills/day once or twice daily (use and dosing per discretion of HCV provider).

Overall Number of Participants Analyzed 108
Median (Full Range)
Unit of Measure: score on a scale
-1.36
(-11.02 to 10.67)
24.Secondary Outcome
Title Change in Functional Status (HCV-PRO) Within Treatment
Hide Description

HCV-PRO score, a validated PROMIS survey used to evaluate overall functioning and well-being in HCV patients, was utilized to compare long-term 'within treatment' changes of functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive estimate (Post treatment to baseline) suggests baseline functional well-being improvement.

Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered.

Time Frame Treatment start date up to 2 years post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who completed HCV-PRO assessments during post-treatment. For this safety analysis, regimen is based on treatment received versus treatment to which patient was randomized. Arms with and without RBV are combined in consideration that usage of RBV was decided by HCV provider and not part of study randomization.
Arm/Group Title EBR/GZR Regimen SOF/LDV Regimen
Hide Arm/Group Description:

Subjects will take EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (dosage and duration per discretion of provider)

Subjects will take 1 tablet SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Overall Number of Participants Analyzed 498 295
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
9 months post treatment
8.02
(3.94 to 12.11)
9.90
(4.27 to 15.52)
20 months post treatment
9.87
(5.48 to 14.27)
11.54
(5.07 to 18.02)
25.Secondary Outcome
Title Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF
Hide Description The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)
Time Frame Treatment start date through treatment completion (up to 24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
As randomized and treated population during Phase 1 and 2 (See Period 1). Analysis based on HCV DAA regimen randomization per study. Differentiation between RBV usage was not included in analysis given that RBV was not part of study randomization but rather decided by HCV provider.
Arm/Group Title EBR/GZR Regimen SOF/LDV Regimen
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir ) tablet once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg to 600mg pill): 1 to 3 pill once or twice daily (dosage and duration per discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg pill: 1 to 3 pills once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.

Overall Number of Participants Analyzed 700 428
Measure Type: Count of Participants
Unit of Measure: Participants
12
   1.7%
4
   0.9%
26.Secondary Outcome
Title HCV SVR Durability -No Cirrhosis
Hide Description Number/Percentage of patients with persistence of viral cure, SVR (SVR = Sustained Virologic Response)- defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
Time Frame 24 weeks post-end of treatment up to 153 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who have HCV RNA result at least 24 weeks after end of treatment regimen as per period 1 (As randomized).
Arm/Group Title EBR/GZR EBR/GZR With Ribavirin SOF/LDV SOF/LDV With RBV PrOD PrOD With RBV
Hide Arm/Group Description:

Patients received EBR/GZV tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks

EBR/GZV (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets, once or twice daily orally with food (use of RBV and dosage at discretion of provider). Total daily dosage ranged from 200 to 1200 mg.

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV)

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider)

RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)

Overall Number of Participants Analyzed 255 17 146 2 14 36
Measure Type: Count of Participants
Unit of Measure: Participants
255
 100.0%
17
 100.0%
146
 100.0%
2
 100.0%
14
 100.0%
36
 100.0%
27.Secondary Outcome
Title HCV SVR Durability-Patients With Cirrhosis
Hide Description Percentage of Cirrhotic patients with persistence of viral cure, SVR, (SVR= Sustained Virologic Response) defined as undetectable HCV RNA at least 24 weeks following HCV Treatment.
Time Frame Up to 132 weeks post HCV treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis limited to patients who had HCV viral load result at least 24 weeks after treatment and analyzed as per randomized (Period 1)
Arm/Group Title EBR/GZR EBR/GZR With RBV SOF/LDV SOF/LDV With RBV PrOD PrOD With RBV
Hide Arm/Group Description:

Patients received EBR/GZR tablet (elbasvir/grazoprevir) once daily for 12 to 16 weeks

EBR/GZR (50/100mg) tablet: 1 tablet once daily with or without food 12 to 16 weeks

Patients received EBR/GZR (elbasvir/grazoprevir) once daily with RBV (Ribavirin) for 12 to 16 weeks

EBR/GZR (50/100mg tablet): 1 tablet once daily with or without food for 12 to 16 weeks (duration per provider discretion) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily (with or without food) for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider) Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily for 12 to 24 weeks (treatment duration as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks

PrOD -(ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV)

ombitasvir/paritaprevir/ritonavir (12.5/75/50mg tablet): 2 tablets once daily with food for 12 to 24 weeks (treatment duration and use of ribavirin as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily with food for 12 to 24 weeks (dosage at discretion of provider)

RBV (200 mg tablet): 1-3 tablets once or twice daily for 12 to 24 weeks (dosage and duration at discretion of provider)

Overall Number of Participants Analyzed 43 7 35 7 6 7
Measure Type: Count of Participants
Unit of Measure: Participants
43
 100.0%
7
 100.0%
35
 100.0%
7
 100.0%
6
 100.0%
7
 100.0%
28.Secondary Outcome
Title Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2
Hide Description Number of participants who achieved SVR (sustained virologic response), defined as undetectable HCV RNA 12 weeks post-treatment with RASs (Resistant Associated Substitutions) after treatment with EBR/GZR or SOF/LDV regimen
Time Frame 12 weeks post HCV treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on as assigned by randomization and patients with available RAS data. Exploratory RAS analysis is grouped by DAA regimen with or without RBV given 1)RBV usage was decided by HCV provider and not part of study randomization and small sample size (limited number of RAS in regimens with RBV)
Arm/Group Title EBR/GZR Regimen SOF/LDV Regimen
Hide Arm/Group Description:

Patients received EBR/GZR (elbasvir/grazoprevir) once daily for 12 to 16 weeks (duration of treatment per provider discretion) with or without Ribavirin (RBV) (per provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food for 12 to 16 weeks

RBV(Ribavirin) (200mg to 600mg tablet): 1 to 3 tablets once or twice daily (usage, dosage and duration per discretion of provider) (Total dosage ranging from 200 mg to 1200 mg daily)

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily 12 to 24 weeks (per discretion of provider) with or without ribavirin (RBV) (per discretion of provider)

SOF/LDV (400/90 mg tablet): 1 tablet once daily with or without food for approximately 12 to 24 weeks (treatment duration per discretion of HCV provider)

Ribavirin (RBV) 200 mg tablet: 1 to 3 tablets once or twice daily orally with food (use of RBV and dosage at discretion of provider)

Overall Number of Participants Analyzed 560 337
Measure Type: Count of Participants
Unit of Measure: Participants
With NS5a RAS Number Analyzed 54 participants 47 participants
47
  87.0%
42
  89.4%
Without NS5a RAS Number Analyzed 506 participants 290 participants
485
  95.8%
286
  98.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBR/GZR Regimen, SOF/LDV Regimen
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Pre-specified equivalence range +/-5%
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-15.3 to 11.3
Estimation Comments [Not Specified]
Time Frame 28 weeks. Adverse events collected up until final viral outcome is determined (approximately 12 weeks after HCV treatment completion).
Adverse Event Reporting Description An adverse event (AE) is any untoward medical occurrence abstracted from the submitted patient medical records. In order to evaluate the safety profiles of the evaluated regimens, all safety analyses were performed based on 'actual treatment received' (as described in Period 2) rather than treatment to which subject was 'randomized'
 
Arm/Group Title EBR/GZR EBR/GZR With RBV SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Hide Arm/Group Description

Patients received EBR/GZR (elbasvir/grazoprevir) tablet once daily without RBV for 12 to 16 weeks (provider discretion)

EBR/GZR: Elbasvir/grazoprevir (50/100mg tablet) 1 tablet once daily with or without food

Patients received EBR/GZR (elbasvir/grazoprevir tablet) tablet once daily with Ribavirin (RBV) for 12 to 16 weeks (provider discretion)

EBR/GZR (Elbasvir/grazoprevir) 50/100mg tablet: 1 tablet once daily with or without food with RBV (200 to 600 mg once or twice daily) for 12 to 16 weeks

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)

SOF/LDV (Sofosbuvir/Ledipasvir) (400/90 mg tablet) 1 tablet taken daily for approximately 12 to 24 weeks with RBV (Ribavirin) 200 mg: 1-3 pills, one to two times daily (dosage at discretion of HCV provider). Total daily dosage ranged fro 200 to 1200 mg.

Patients received SOF/LDV (sofosbuvir/ledipasvir) orally once daily with or without food 12 to 24 weeks (treatment duration per discretion of provider)

SOF/LDV (Sofosbuvir/Ledipasvir )(400/90 mg tablet) 1 tablet orally taken daily for approximately 12 to 24 weeks

PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks with Ribavirin (RBV) (treatment at duration provider discretion)

ombitasvir/paritaprevir/ritonavir: 2 tablets orally once daily (12.5/75/50mg) for 12 to 24 weeks

Dasabuvir (250 mg tablet): 1 tablet orally once or twice daily for 12 to 24 weeks Ribavirin (200 mg pill): 200 to 600 mg once or twice daily (dosage at provider discretion). Total daily dosage ranged from 200 to 1200 mg.

Patients received PrOD orally (ombitasvir/paritaprevir/ritonavir and dasabuvir) daily for 12 to 24 weeks without Ribavirin (RBV) (provider discretion)

Ombitasvir/paritaprevir/ritonavir (12.5/75/50mg): 2 tablets taken once orally daily for 12 to 24 weeks (treatment duration as per HCV provider)

Dasabuvir (250 mg tablet): 1 tablet once or twice daily for 12 to 24 weeks

All-Cause Mortality
EBR/GZR EBR/GZR With RBV SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/664 (0.90%)      0/56 (0.00%)      0/15 (0.00%)      4/394 (1.02%)      1/99 (1.01%)      0/47 (0.00%)    
Hide Serious Adverse Events
EBR/GZR EBR/GZR With RBV SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/664 (4.52%)      2/56 (3.57%)      0/15 (0.00%)      6/394 (1.52%)      5/99 (5.05%)      0/47 (0.00%)    
Cardiac disorders             
Chest Pain  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 1/99 (1.01%)  1 0/47 (0.00%)  0
Gastrointestinal disorders             
Abdominal Pain  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Femoral hernia, obstructive  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Gastric ulcer perforation  1 [1]  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Gastrointestinal haemorrhage  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Small intestinal obstruction  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
General disorders             
Drug Withdrawal Syndrome  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Immune system disorders             
Hypersensitivity  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Infections and infestations             
Cellulitis  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Gastroenteritis viral  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Hepatitis B  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Osteomyelitis  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 1/99 (1.01%)  1 0/47 (0.00%)  0
Pneumonia  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 3/394 (0.76%)  3 0/99 (0.00%)  0 0/47 (0.00%)  0
Injury, poisoning and procedural complications             
Fall  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Gun shot wound  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Hip fracture  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Overdose  1  2/664 (0.30%)  2 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 1/99 (1.01%)  1 0/47 (0.00%)  0
Road traffic accident  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Thermal burn  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Toxicity to various agents  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Metabolism and nutrition disorders             
Gout  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Back Pain  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Pain in Extremity  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Neuroendocrine carcinoma  1  0/664 (0.00%)  0 1/56 (1.79%)  1 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Papillary thyroid cancer  1  0/664 (0.00%)  0 1/56 (1.79%)  1 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Nervous system disorders             
Adjustment Disorder  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Cerebrovascular Accident  2  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Haemorrhagic stroke  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Neuropathy peripheral  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Spinal Hematoma  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Syncope  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 1/99 (1.01%)  1 0/47 (0.00%)  0
Psychiatric disorders             
Alcohol withdrawal Syndrome  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Completed Suicide  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 1/99 (1.01%)  1 0/47 (0.00%)  0
Drug Abuse  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 1/99 (1.01%)  1 0/47 (0.00%)  0
Mania  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Mental status change  2  2/664 (0.30%)  2 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Self-injurious ideation  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Renal and urinary disorders             
Renal failure acute  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Chronic Obstructive Pulmonary Disease  2  2/664 (0.30%)  2 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Dyspnoea  1  2/664 (0.30%)  2 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Respiratory failure  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Surgical and medical procedures             
Drug Detoxification  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Vascular disorders             
Arteriovenous fistula  1  1/664 (0.15%)  1 0/56 (0.00%)  0 0/15 (0.00%)  0 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Deep Vein Thrombosis  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
Peripheral ischaemia  1  0/664 (0.00%)  0 0/56 (0.00%)  0 0/15 (0.00%)  0 1/394 (0.25%)  1 0/99 (0.00%)  0 0/47 (0.00%)  0
1
Term from vocabulary, MedDRA (15.1)
2
Term from vocabulary, MedDra
Indicates events were collected by systematic assessment
[1]
Gastric ulcer perforation
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
EBR/GZR EBR/GZR With RBV SOF/LDV With RBV SOF/LDV PrOD With RBV PrOD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   298/664 (44.88%)      46/56 (82.14%)      8/15 (53.33%)      184/394 (46.70%)      74/99 (74.75%)      32/47 (68.09%)    
Blood and lymphatic system disorders             
Anaemia  1 [1]  2/664 (0.30%)  2 17/56 (30.36%)  17 2/15 (13.33%)  2 0/394 (0.00%)  0 20/99 (20.20%)  20 0/47 (0.00%)  0
Cardiac disorders             
Chest Pain  1  10/664 (1.51%)  10 1/56 (1.79%)  1 1/15 (6.67%)  1 9/394 (2.28%)  9 3/99 (3.03%)  3 0/47 (0.00%)  0
Gastrointestinal disorders             
Abdominal discomfort  1  7/664 (1.05%)  7 1/56 (1.79%)  1 1/15 (6.67%)  1 2/394 (0.51%)  2 3/99 (3.03%)  3 0/47 (0.00%)  0
Nausea  1  54/664 (8.13%)  54 12/56 (21.43%)  12 3/15 (20.00%)  3 34/394 (8.63%)  34 23/99 (23.23%)  23 5/47 (10.64%)  5
Diarrhoea  1  45/664 (6.78%)  45 3/56 (5.36%)  3 2/15 (13.33%)  2 19/394 (4.82%)  19 5/99 (5.05%)  5 3/47 (6.38%)  3
Abdominal Pain  1  11/664 (1.66%)  11 5/56 (8.93%)  5 1/15 (6.67%)  1 11/394 (2.79%)  11 3/99 (3.03%)  3 0/47 (0.00%)  0
Constipation  1  16/664 (2.41%)  16 5/56 (8.93%)  5 0/15 (0.00%)  0 12/394 (3.05%)  12 2/99 (2.02%)  2 2/47 (4.26%)  2
Dyspepsia  1  5/664 (0.75%)  5 4/56 (7.14%)  4 1/15 (6.67%)  1 3/394 (0.76%)  3 0/99 (0.00%)  0 2/47 (4.26%)  2
Vomiting  1  13/664 (1.96%)  13 3/56 (5.36%)  3 0/15 (0.00%)  0 13/394 (3.30%)  13 8/99 (8.08%)  8 1/47 (2.13%)  1
Abdominal Pain Upper  1  8/664 (1.20%)  8 2/56 (3.57%)  2 1/15 (6.67%)  1 9/394 (2.28%)  9 1/99 (1.01%)  1 1/47 (2.13%)  1
Decreased Appetite  1  9/664 (1.36%)  9 2/56 (3.57%)  2 1/15 (6.67%)  1 5/394 (1.27%)  5 3/99 (3.03%)  3 2/47 (4.26%)  2
Hepatobiliary disorders             
Hyperbilirubinaemia  1  0/664 (0.00%)  0 3/56 (5.36%)  3 0/15 (0.00%)  0 0/394 (0.00%)  0 1/99 (1.01%)  1 0/47 (0.00%)  0
Cholelithiasis  1  0/664 (0.00%)  0 0/56 (0.00%)  0 1/15 (6.67%)  1 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Infections and infestations             
Influenza like illness  1  18/664 (2.71%)  18 3/56 (5.36%)  3 0/15 (0.00%)  0 7/394 (1.78%)  7 2/99 (2.02%)  2 0/47 (0.00%)  0
Injury, poisoning and procedural complications             
Fall  1  3/664 (0.45%)  3 0/56 (0.00%)  0 1/15 (6.67%)  1 3/394 (0.76%)  3 0/99 (0.00%)  0 0/47 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Back Pain  1  15/664 (2.26%)  15 3/56 (5.36%)  3 0/15 (0.00%)  0 12/394 (3.05%)  12 0/99 (0.00%)  0 0/47 (0.00%)  0
Arthralgia  1  17/664 (2.56%)  17 1/56 (1.79%)  1 1/15 (6.67%)  1 13/394 (3.30%)  13 4/99 (4.04%)  4 0/47 (0.00%)  0
Musculoskeletal Pain  1  2/664 (0.30%)  2 1/56 (1.79%)  1 1/15 (6.67%)  1 3/394 (0.76%)  3 0/99 (0.00%)  0 0/47 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Prostate Cancer  1  0/664 (0.00%)  0 0/56 (0.00%)  0 1/15 (6.67%)  1 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Nervous system disorders             
Dizziness  1  15/664 (2.26%)  15 7/56 (12.50%)  7 0/15 (0.00%)  0 11/394 (2.79%)  11 3/99 (3.03%)  3 1/47 (2.13%)  1
Fatigue  1  105/664 (15.81%)  105 18/56 (32.14%)  18 5/15 (33.33%)  5 82/394 (20.81%)  82 35/99 (35.35%)  35 5/47 (10.64%)  5
Headache  1  94/664 (14.16%)  94 12/56 (21.43%)  12 1/15 (6.67%)  1 68/394 (17.26%)  68 15/99 (15.15%)  15 9/47 (19.15%)  9
Insomnia  1  26/664 (3.92%)  26 6/56 (10.71%)  6 1/15 (6.67%)  1 10/394 (2.54%)  10 8/99 (8.08%)  8 3/47 (6.38%)  3
Tremor  1  0/664 (0.00%)  0 0/56 (0.00%)  0 1/15 (6.67%)  1 0/394 (0.00%)  0 0/99 (0.00%)  0 0/47 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Dyspnoea  1 [2]  9/664 (1.36%)  9 8/56 (14.29%)  8 0/15 (0.00%)  0 11/394 (2.79%)  11 9/99 (9.09%)  9 1/47 (2.13%)  1
Bronchitis  1  5/664 (0.75%)  5 3/56 (5.36%)  3 0/15 (0.00%)  0 2/394 (0.51%)  2 2/99 (2.02%)  2 0/47 (0.00%)  0
Cough  1  15/664 (2.26%)  15 3/56 (5.36%)  3 0/15 (0.00%)  0 14/394 (3.55%)  14 3/99 (3.03%)  3 0/47 (0.00%)  0
Nasal Congestion  1  2/664 (0.30%)  2 0/56 (0.00%)  0 1/15 (6.67%)  1 3/394 (0.76%)  3 0/99 (0.00%)  0 0/47 (0.00%)  0
Skin and subcutaneous tissue disorders             
Pruritus  1  10/664 (1.51%)  10 3/56 (5.36%)  3 0/15 (0.00%)  0 2/394 (0.51%)  2 4/99 (4.04%)  4 4/47 (8.51%)  4
Rash  1  10/664 (1.51%)  10 2/56 (3.57%)  2 1/15 (6.67%)  1 5/394 (1.27%)  5 3/99 (3.03%)  3 3/47 (6.38%)  3
Vascular disorders             
Oedema Peripheral  1 [3]  12/664 (1.81%)  12 1/56 (1.79%)  1 1/15 (6.67%)  1 4/394 (1.02%)  4 1/99 (1.01%)  1 0/47 (0.00%)  0
1
Term from vocabulary, MedDRA (15.1)
Indicates events were collected by systematic assessment
[1]
Anemia
[2]
Dyspnea
[3]
Peripheral edema Edema Peripheral
This pragmatic trial allowed patients who were randomized to SOF/LDV but unable to obtain SOF/LDV (due to limitations in access from insurance, etc.) to be treated with the accessible, alternative DAA regimens. This contributed to the variance from 'as randomized' population to the 'as treated' population. Rapidly changing HCV landscape led to discontinuation of PrOD treatment regimen and modification of initial analysis plan including reduction of original sample size.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Lauren Morelli
Organization: UF Hepatology Research at CTRB
Phone: 352-273-9508
EMail: lauren.morelli@medicine.ufl.edu
Layout table for additonal information
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02786537    
Other Study ID Numbers: 16-1234
PCORI-1503-27891 ( Other Identifier: PCORI )
IRB201501162 ( Other Identifier: New UF IRB-01 )
First Submitted: May 17, 2016
First Posted: June 1, 2016
Results First Submitted: May 26, 2020
Results First Posted: November 24, 2020
Last Update Posted: December 6, 2021