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)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 3

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
    

Intervention name(s): Narlaprevir; Ritonavir; Placebo Narlaprevir; Placebo Ritonavir; Pegylated interferon alfa-2a/ Pegylated interferon alfa-2b; Ribavirin
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): yellow film-coated 100 mg. tablets; 100 mg tablets encapsulates in gelatin capsules (for blinding purposes); yellow film-coated 100 mg. tablets identical to Narlaprevir tablets; 100 mg lactose/ cellulose tablets encapsulated in gelatin capsules (for blinding purposes) identical to Ritonavir capsules; 180µg for subcutaneous injections in 0.5 ml syrettes / 1.5 µg/kg for subcutaneous injections in 50µkg, 80µkg,100µkg, 120µkg, 150µkg in vials; 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
Other intervention name(s): Norvir; Pegasys; PegIntron; Rebetol
Intervention MeSH terms: Interferons; Ritonavir; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a; Peginterferon alfa-2b
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment