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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 : Active, not recruiting
First Posted : June 1, 2016
Results First Posted : November 24, 2020
Last Update Posted : November 24, 2020
Sponsor:
Collaborators:
Patient-Centered Outcomes Research Institute
Merck Sharp & Dohme Corp.
AbbVie
Information provided by (Responsible Party):
University of Florida

Brief Summary:
Phase 1 of this study will compare the effectiveness of 3 approved HCV treatment regimens to learn whether they work equally well under real-world conditions. Phase 2 of this study will begin early 2017 and will compare the effectiveness of 2 FDA approved HCV treatments. Patients receiving HCV therapy in community and academic clinics will be offered the opportunity to consent to be randomly assigned to one of three regimens and then observed for outcomes. Once randomized, all medical care, laboratory testing, and any disease or side effect management will be assumed by usual care conditions, and patient-reported outcomes will be collected outside clinic in keeping with pragmatic design principles.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Drug: sofosbuvir/ledipasvir Drug: ombitasvir/paritaprevir/ritonavir (Phase 1 only) Drug: elbasvir/grazoprevir Drug: Dasabuvir Drug: Ribavirin Phase 4

Detailed Description:

In Phase 1 of this study, consented subjects will be randomized to 1 of the following 3 HCV treatments:

1) Harvoni® 2)Viekira Pak™ 3)Zepatier™ (The addition of Ribavirin and the length of treatment will be determined by the provider). In Phase 2 of this study, consented subjects will be randomized to 1 of 2 FDA approved HCV treatments: 1)1) Harvoni® or 3)Zepatier™. Both Phase 1 and Phase 2 subjects will have up to 1 tablespoon of blood drawn for HCV resistance testing and future biorepository testing (if subject provides additional consent). The results of testing will determine whether a genotype 1a subject will be provided 12 or 16 wks of Zepatier (if randomized to Zepatier).

Following randomization, subjects will complete patient reported outcome questionnaires via electronic device or telephone. Following randomization, subjects will be asked to complete surveys again at Wk 4 of treatment, End of Treatment, 1 and 3 year post treatment. Subjects standard medical care will continue. Test results and medical records throughout treatment and for up to 3 years post treatment will be collected.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1275 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: THE PRIORITIZE STUDY: A Pragmatic, Randomized Study of Oral Regimens for Hepatitis C: Transforming Decision-Making for Patients, Providers, and Stakeholders
Study Start Date : June 2016
Actual Primary Completion Date : June 13, 2019
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: elbasvir/grazoprevir tablet with RBV
Subjects will take elbasvir/grazoprevir tablet tablet once daily with Ribavirin (RBV) for 12 to 16 weeks (provider discretion)
Drug: elbasvir/grazoprevir
Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks with or without RBV
Other Name: Zepatier (elbasvir/grazoprevir)

Drug: Ribavirin
Add discretion of provider, Ribavirin at dosages ranging from 200mg to 600 mg daily (or twice daily) can be added to HCV treatment regimen
Other Name: RBV

Active Comparator: elbasvir/grazoprevir tablet
Subjects will take elbasvir/grazoprevir tablet tablet once daily without RBV for 12 to 16 weeks (provider discretion)
Drug: elbasvir/grazoprevir
Elbasvir/grazoprevir (50/100mg) tablet once daily with or without food with or without RBV for 12 to 16 weeks with or without RBV
Other Name: Zepatier (elbasvir/grazoprevir)

Active Comparator: sofosbuvir/ledipasvir with Ribavirin
Subjects will take 1 tablet sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks with ribavirin (RBV) (per discretion of provider)
Drug: 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)
Other Name: Harvoni® (sofosbuvir/ledipasvir)

Drug: Ribavirin
Add discretion of provider, Ribavirin at dosages ranging from 200mg to 600 mg daily (or twice daily) can be added to HCV treatment regimen
Other Name: RBV

Active Comparator: sofosbuvir/ledipasvir
Subjects will take 1 tablet sofosbuvir/ledipasvir orally once daily with or without food 12 to 24 weeks without ribavirin (RBV) (per discretion of provider)
Drug: 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)
Other Name: Harvoni® (sofosbuvir/ledipasvir)

Active Comparator: ombitasvir/paritaprevir/ritonavir & dasabuvir & Ribavirin
Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks and Ribavirin (use and dosage at provider discretion)
Drug: 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)
Other Name: Viekira Pak (fixed dose combination of ombitasvir/paritaprevir/ritonavir) (Phase 1 only)

Active Comparator: ombitasvir/paritaprevir/ritonavir & dasabuvir (Phase 1 only)
Two ombitasvir/paritaprevir/ritonavir once daily and dasabuvir twice daily for 12 to 24 weeks without Ribavirin (at provider discretion)
Drug: 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)
Other Name: Viekira Pak (fixed dose combination of ombitasvir/paritaprevir/ritonavir) (Phase 1 only)

Drug: Dasabuvir
250 mg daily for 12 to 24 weeks
Other Name: Viekira Pak




Primary Outcome Measures :
  1. Number of Participants With Sustained Virologic Response (SVR12) mITT With Imputation [ Time Frame: 12 weeks post-treatment ]
    SVR (Sustained Virologic Treatment) 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) mITT with imputation. Number of subjects reflects participants from both Phase 1 and 2 as per Period 1.

  2. Number of Participants With Sustained Virologic Response (SVR12-mITT) [ Time Frame: 12-24 weeks post HCV treatment ]

    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 from both Phase 1 and 2.


  3. Drug Side Effects-Headache [ Time Frame: Baseline and Average On-Treatment Score ]

    Side effects will be collected from validated, Patient Reported Outcomes surveys (PROs) 'PROMIS Fatigue and Nausea, Headache Impact Test (HIT)' For each PROMIS score of interest (Headache, Nausea/vomiting, and Fatigue), change will be compared using difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as difference from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. PROMIS Measurements: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always (Worst Score).

    Number of subjects reflects participants from both Phase 1 and 2.


  4. Change in Nausea/Vomiting PROMIS Score [ Time Frame: Baseline and Average On-Treatment Score ]

    Side effects will be collected from validated, Patient Reported Outcomes surveys (PROs) 'PROMIS Fatigue and Nausea, Headache Impact Test (HIT)' For each PROMIS score of interest (Headache, Nausea/vomiting, and Fatigue), change will be compared using difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as difference from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being.

    PROMIS measurements: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always (worst outcome). A negative (-) PROMIS change score for Headache, Nausea and Fatigue is suggestive of symptom improvement or lack of drug side effect. Number of subjects reflects participants from both Phase 1 and 2.


  5. Change in PRO Drug Side Effect Fatigue T-Score [ Time Frame: Baseline and Average On-Treatment Score ]
    Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated by exporting raw scores and uploading to www.healthmeasures.net in order 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 for Headache, Nausea and Fatigue 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.

  6. Change in HCV-PRO (Functional Well-being) Score [ Time Frame: End of Treatment - Baseline ]

    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 will be used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2.


  7. 16 Wk Elbasvir/Grazobevir RBV Efficacy With RAPs [ Time Frame: 12 weeks post treatment ]

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

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



Secondary Outcome Measures :
  1. Treatment Adherence [ Time Frame: 12-16 weeks of HCV treatment ]

    Comparison of number of patients who report missing pills (doses) (Voils' Medication Adherence Survey) per general treatment regimen: 1)EBR/GZV (elbasvir/grazoprevir) 2)SOF/LDV (sofosbuvir/ledipasvir) 3)PrOD Arms were compared across primary treatment (regardless of use of ribavirin within each arm).

    Limited to Patients who started up to to the last date of last PrOD patient start (January 2017)--Phase 1


  2. Number of Patients With Decrease in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation [ Time Frame: 1 and 3 years post treatment discontinuation ]
    6 PROMIS scores recorded at baseline and at 1 and 3 years after treatment will be used to evaluate change from baseline.

  3. Number of Patients With Reduction in Fibrosis 3 Years (Liver Biopsy/Fibroscan) Post Treatment Baseline [ Time Frame: 3 years post treatment discontinuation ]
    Number of patients with reduction in Liver Biopsy Scores/Fibroscan Scores will be assessed by comparing baseline and post-treatment liver biopsy/fibroscan scores

  4. 3 Year SVR [ Time Frame: 3 years after treatment discontinuation ]
    Percentage of patients who are still HCV RNA undetectable 3 years post HCV treatment

  5. Percentage of Patients Who Have an Increase in Functional Status (as Reported on HCV-PRO Questionnaire) [ Time Frame: Baseline, 1 year, and 2 years after treatment discontinuation ]
    Percentage of patients who have an increase in functional status (as reported on patient reported outcomes)

  6. Number of Participants With Adverse Events That Caused Treatment Discontinuation [ Time Frame: Treatment start date through treatment completion (up to 24 weeks) ]
    The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HCV Genotype 1a or 1b
  • Adult patients (age 18 years or older)
  • Patients being prescribed HCV treatment who can begin treatment with any of the three HCV treatments being studied (Harvoni, Viekira Pak (Phase 1 only), or Zepatier)

Exclusion Criteria:

  • Inability to provide written informed consent
  • HARVONI® is not a covered drug on benefits formulary
  • Current or historical evidence of hepatic decompensation (variceal bleeding, hepatic encephalopathy, or ascites)
  • Child Pugh (CTP) B or C Cirrhosis (documented CTP calculation is required)
  • Pregnant or breastfeeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02786537


Locations
Show Show 38 study locations
Sponsors and Collaborators
University of Florida
Patient-Centered Outcomes Research Institute
Merck Sharp & Dohme Corp.
AbbVie
Investigators
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Principal Investigator: David R Nelson, MD University of Florida
  Study Documents (Full-Text)

Documents provided by University of Florida:
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02786537    
Other Study ID Numbers: 16-1234
First Posted: June 1, 2016    Key Record Dates
Results First Posted: November 24, 2020
Last Update Posted: November 24, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Florida:
Hepatitis C
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Ritonavir
Ribavirin
Sofosbuvir
MK-5172
Ledipasvir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antimetabolites