NCT03833362

Efficacy and Safety of Narlaprevir Used in Combination With Ritonavir in Treatment-Naïve and Failed Prior Treatment With Pegylated Interferon/Ribavirin Patients With Chronic Hepatitis C Genotype 1 (PIONEER - Study)

International, Multicenter, Randomized, Double Blind, Active-controlled, Parallel-group Phase III Study of Narlaprevir/Ritonavir and Pegylated Interferon/Ribavirin in 2 Patient Populations - naïve and Treatment Failure Patients With Genotype 1 Chronic Hepatitis C

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 420 (actual)
• Sponsor: R-Pharm · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to confirm that combination of narlaprevir (NVR) and ritonavir (RTV) used as a metabolic inhibitor with pegylated interferon (PEG-INF) and ribavirin (RBV) leads to a superior Sustained Virological Response (SVR) rate compared to treatment with pegylated interferon and ribavirin in treatment-naïve and treatment failure patient populations.

Detailed description

The study included 3 time periods: * Screening period with duration up to 3 weeks during which study eligibility was confirmed. * Double-blind treatment period: all eligible patients divided into Treatment naive and Previous treatment failure subpopulations were randomized in one of the two parallel treatment arms in 2:1 ratio: 1. Arm 1: All patients received the combination of NVR/RTV + PEG-INF/RBV for 12 weeks that was followed by PEG-INF and RBV for 12 weeks (total treatment duration of 24 weeks). 2. Arm 2: Therapy with PEG-INF and RBV (standard of care) for 48 weeks with placebo equivalent for NVR and RTV for the first 12 weeks. Different types of pegylated interferon could be used for treatment. The assignment to the pegylated interferon alfa-2a or pegylated interferon alfa-2b treatment will be also performed using web system, in a 1:1 ratio. Clinical efficacy of each arm were assessed 24 weeks after the end of treatment with undetectable hepatitis C virus (HCV) RNA by lower limit of detection (LOD) 24 weeks following the end of treatment. In case of serum HCV-RNA levels were greater than or equal to 100 IU/mL at Week 12 of treatment (Arm 1) or serum HCV RNA declined from baseline less than 2 log after 12 weeks of treatment or serum HCV-RNA levels ≥LOD at week 24 of treatment (Arm 2) patients were considered non-responders and discontinued participation in the study. In case of satisfactory treatment response all patients were additionally administered with PEG-INF/RBV for 12 weeks (total of 24 weeks of treatment) in Arm 1, and for 36 weeks (total of 48 weeks of treatment) in Arm 2. * Follow-up period during which patients do not receive any study medication. The duration of the follow-up period after the end of study treatment will be 24 weeks. Overall, each patient will participate in the study for approximately up to 75 weeks from the time the patient signs the Informed Consent Form through the final visit

Conditions

• Hepatitis C

Interventions

Type	Name	Description
DRUG	Narlaprevir	yellow film-coated 100 mg. tablets
DRUG	Ritonavir	100 mg tablets encapsulates in gelatin capsules (for blinding purposes)
DRUG	Placebo Narlaprevir	yellow film-coated 100 mg. tablets identical to Narlaprevir tablets
DRUG	Placebo Ritonavir	100 mg lactose/ cellulose tablets encapsulated in gelatin capsules (for blinding purposes) identical to Ritonavir capsules
DRUG	Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b	180µg for subcutaneous injections in 0.5 ml syrettes / 1.5 µg/kg for subcutaneous injections in 50µkg, 80µkg,100µkg, 120µkg, 150µkg in vials
DRUG	Ribavirin	hard gelatin, white 200mg. capsules Weight-based dose was 1000 mg/day (patient weight \<75 kg) or 1200 mg/day (patient weight ≥75 kg) with Peginterferon alfa-2a and 800 mg/day (patient weight \<65 kg) - 1400 (patient weight \>105 kg) mg/day with Peginterferon alfa-2b

Timeline

• Start date: 2014-05-07
• Primary completion: 2016-03-23
• Completion: 2017-02-21
• First posted: 2019-02-07
• Last updated: 2019-02-07

Locations

20 sites across 1 country: Russia