Study of Oral Treatments for Hepatitis C (PRIORITIZE)

University of Florida

Status and phase: Completed; Phase 4

Conditions: Chronic Hepatitis C

Treatments: Drug: EBR/GZR (elbasvir/grazoprevir); Drug: SOF/LDV (sofosbuvir/ledipasvir); Drug: Ribavirin; Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02786537

PCORI-1503-27891 (Other Identifier)

16-1234

IRB201501162 (Other Identifier)

Details and patient eligibility

About

Phase 1 of this study compared the effectiveness of 3 approved DAA (direct-acting antiviral) HCV treatment regimens to learn whether they worked equally well under real-world conditions. Phase 2 of this study began early 2017 with removal of 1 DAA regimen, limiting randomization to just 2 FDA approved DAA regimens. Patients receiving HCV therapy in community and academic clinics were offered the opportunity to consent to be randomly assigned to one of three (phase 1) or one of two (phase 2) regimens and observed for outcomes. Once randomized, all medical care, laboratory testing, and any disease or side effect management were assumed by usual care conditions, and patient-reported outcomes were collected outside clinic in keeping with pragmatic design principles.

Full description

In Phase 1 of this study, consented patients were randomized to 1 of the following 3 HCV DAA treatments: 1) Harvoni® (SOF/LDV) 2) Viekira Pak™ (PrOD) 3) Zepatier™ (EBR/GZR) with the optional addition of Ribavirin (RBV) and the length of treatment determined by the individual provider.

In Phase 2 of this study, consented patients were randomized to 1 of 2 FDA approved HCV treatments: Harvoni® or Zepatier™. Both Phase 1 and Phase 2 subjects had up to 1 tablespoon of blood drawn for HCV resistance testing and future biorepository testing (following appropriate additional consent). The results of testing determined whether a genotype 1a subject randomized to Zepatier would be provided 12 or 16 wks of Zepatier.

Following enrollment/randomization, participants completed patient reported outcome questionnaires (PROs) via electronic device or telephone. Following baseline/randomization, participants were asked to complete surveys again at Wk 4 of treatment, End of Treatment, 1 and 3 year post treatment. Patients continued standard medical care throughout study. Data was abstracted from test results and medical records throughout treatment and for up to 3 years post treatment.

Enrollment: 1,275 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 (SOF/LDV), Viekira Pak (PrOD) (Phase 1 only), or Zepatier (EBR/GZR))

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,275 participants in 6 patient groups

EBR/GZR (elbasvir/grazoprevir) with RBV

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

Treatment:

Drug: Ribavirin

Drug: EBR/GZR (elbasvir/grazoprevir)

EBR/GZR (elbasvir/grazoprevir)

Active Comparator group

Description:

Patients received 1 EBR/GZR (elbasvir/grazoprevir) tablet (50/100 mg) once daily for 12 to 16 weeks (provider discretion) (without Ribavirin)

Treatment:

Drug: EBR/GZR (elbasvir/grazoprevir)

SOF/LDV (sofosbuvir/ledipasvir) with RBV

Active Comparator group

Description:

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) (at discretion of provider). RBV taken as 200 mg/tablet(capsule), 1-3 pills/day, 1-2 times/day.

Treatment:

Drug: Ribavirin

Drug: SOF/LDV (sofosbuvir/ledipasvir)

SOF/LDV (sofosbuvir/ledipasvir)

Active Comparator group

Description:

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)

Treatment:

Drug: SOF/LDV (sofosbuvir/ledipasvir)

PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) with RBV (Phase 1 only)

Active Comparator group

Description:

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.

Treatment:

Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only)

PrOD (ombitasvir/paritaprevir/ritonavir and dasabuvir)

Active Comparator group

Description:

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)

Treatment:

Drug: PrOD (ombitasvir/paritaprevir/ritonavir with dasabuvir) (Phase 1 only)

Drug: Ribavirin