Trial of Simplified Treatment Monitoring for 8 Weeks Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: glecaprevir (300mg)/pibrentasvir (120mg)
Intervention description: glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 380.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The aim of this study is to determine if treatment monitoring schedule for chronic HCV
      patients treated with glecaprevir (300mg)/pibrentasvir (120mg) can be simplified.

      Data has shown that direct acting antiviral (DAA) regimen of glecaprevir (300mg)/pibrentasvir
      (120mg), a protease inhibitor and NS5A inhibitor respectively , provides key features for HCV
      treatment simplification.

      Eligible participants (naïve pre-cirrhosis chronic HCV patients) will be randomized (1:2) to
      the standard or simplified monitoring arm and will receive treatment for 8 weeks.

      One post treatment visit will be conducted 12 weeks after the final dose of study medication
      to evaluate the proportion of patients with undetectable HCV RNA at this timepoint (SVR12).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have voluntarily signed the informed consent form.

          2. 18 years of age or older.

          3. Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater
             than 6 months.

          4. HCV RNA plasma ≥ 10,000 IU/ml at screening.

          5. HCV genotype 1-6.

          6. HCV treatment naïve (no prior treatment with an approved or investigation anti-HCV
             medication).

          7. Stage F0-3, based on: hepatic elastography <12.5 kPa on Fibroscan® or APRI <1.0.

          8. If co-infection with HIV is documented, the subject must meet the following criteria:

               -  ART naïve with CD4 T cell count >500 cells/mm3; OR

               -  On a stable ART regimen (containing only permissible ART - see protocol section
                  3.2) for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3
                  and a plasma HIV RNA level below the limit of detection.

          9. Negative pregnancy test at screening and baseline (females of childbearing potential
             only).

         10. All fertile females must be using effective contraception during treatment and during
             the 30 days after treatment end.

        Exclusion Criteria:

          1. History of any of the following:

               1. Clinically significant illness (other than HCV) or any other major medical
                  disorder that may interfere with the participant treatment, assessment or
                  compliance with the protocol; participants currently under evaluation for a
                  potentially clinically significant illness (other than HCV) are also excluded.

               2. Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal
                  haemorrhage).

               3. Solid organ transplant.

               4. History of severe, life-threatening or other significant sensitivity to any
                  excipients of the study drugs.

          2. Any of the following lab parameters at screening:

               1. ALT > 10 x ULN

               2. AST > 10 x ULN

               3. Direct bilirubin > ULN

               4. Platelets < 90,000/μL (cells/mm3) if Fibroscan® <12.5 kPa OR < 150,000/μL
                  (cells/mm3) if Fibroscan® is unavailable and patient is included with APRI <1

               5. Creatinine clearance (CLcr) < 50 mL/min

               6. Haemoglobin < 12g/dL for males; <11g/dL for females

               7. Albumin < LLN

               8. INR > 1.5 ULN unless subject has known haemophilia or is stable on an
                  anticoagulant regimen affecting INR

          3. Pregnant or breastfeeding female.

          4. HBV infection (HBsAg positive).

          5. Use of prohibited concomitant medications as described in protocol section 5.2.

          6. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone
             equivalent > 10 mg/day for >2 weeks).

          7. Therapy with any anti-neoplastic or immunomodulatory treatment (including
             supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of
             study drug.

          8. Any investigational drug ≤6 weeks prior to the first dose of study drug.

          9. Ongoing severe psychiatric disease as judged by the treating physician.

         10. Positive result of a urine drug screen at the Screening Visit for opiates,
             barbiturates, amphetamines, cocaine, benzodiazepines, phencyclidine, propoxyphene, or
             alcohol, with the exception of a positive result (including methadone) associated with
             documented short-term use or chronic stable use of a prescribed medication in that
             class.

         11. Injecting drug use within the previous six months.

         12. Inability or unwillingness to provide informed consent or abide by the requirements of
             the study.