A Phase 2, Multicenter, Randomized, Open-label, Dose-ranging Study to Evaluate the Efficacy and Safety of TG-2349 in Combination with Peg-interferon and Ribavirin in Treatment Naïve East Asian Subjects with Chronic Hepatitis C Virus Genotype 1b Infection.
It is a multicenter, randomized, open-label study to evaluate the safety, tolerability, and antiviral efficacy of two different doses of TG-2349 combined with Peg-interferon (IFN) and Ribavirin (RBV) in HCV-GT1b treatment naïve East Asian subjects. The treatment duration of TG-2349+IFN+RBV is 12 weeks, with or without an additional 12-week treatment of IFN+RBV, depending on HCV RNA level at On-Treatment Week 4. Approximately 24 subjects will be randomized (1:1) to one of the following 2 treatment groups: * Group I (n=12): 200 mg TG-2349 (2 capsules) + IFN + RBV * Group II (n=12): 400 mg TG-2349 (4 capsules) + IFN + RBV Randomization will be stratified by IL28B genotype "CC" or "non-CC". Subjects with HCV RNA \< LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at Week 4 will receive 12 weeks of TG-2349+IFN+RBV treatment. Subjects with HCV RNA ≥ LLOQ but \< 100 IU/mL at Week 4 will receive 12 weeks of TG-2349+IFN+RBV treatment followed by an additional 12 weeks of IFN+RBV treatment. However, subjects with HCV RNA ≥ 100 IU/mL at Week 4 will discontinue the study treatment and complete the Early-Termination (ET) visit. The study will be terminated if 3 or more of the first 12 subjects enrolled across both Groups I and II, or ≥ 25% of subjects thereafter, fail to respond to treatment (i.e., confirmed on-treatment virologic failure or post-treatment relapse). Patients, except those who have achieved SVR12, will be offered the standard of care with Peg-interferon and Ribavirin for duration of 24, 48, or 72 weeks based on Taiwan's regulatory guideline and principal investigator's judgment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
TG-2349 (Furaprevir) is available as a Swedish orange capsule (size 0) for oral administration. Each capsule contains an equivalent of 100 mg of TG-2349 spray dried solid (SDD) and the following inactive ingredients: microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate, and colloidal silicon oxide.
RBV (Ribavirin or COPEGUS®) is available as a light pink to pink colored, flat, oval-shaped, film-coated tablet for oral administration. Each tablet contains 200 mg of ribavirin and the following inactive ingredients: pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, cornstarch, and magnesium stearate. The coating of the tablet contains Chromatone-P® or Opadry® Pink (made by using hydroxypropyl methyl cellulose, talc, titanium dioxide, synthetic yellow iron oxide, and synthetic red iron oxide), ethyl cellulose (ECD-30), and triacetin.
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
Proportion of Subjects Achieving Sustained Viral Response at 12 Weeks After the End of Treatment.
Proportion of subjects with HCV RNA\< LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at 12 weeks after the end of treatment (SVR12) in the Full Analysis Set (FAS) population, which include subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.
Time frame: 12 weeks after the end of treatment (SVR12), after 12-week treatments
Proportion of Subjects Achieving Sustained Viral Response at 4, 8, and 24 Weeks After the End of Treatment (SVR4, SVR8, and SVR24)
Time frame: 4, 8, 24 weeks after the end of treatment (SVR4, 8, 24), after 12-week treatments
Proportion of Subjects Achieving HCV RNA < Lower Limit of Quantification, Target Detected or Target Not Detected (< LLOQ, TD or TND)
Time frame: The whole treatment period, 12 weeks
Proportion of Subjects Achieving HCV RNA < LLOQ, TND
Time frame: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)
Mean Absolute Values in HCV RNA (log10 IU/mL)
Time frame: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)
Proportion of Subjects Experiencing Virologic Failure During Treatment and Viral Relapse After the End of Treatment.
Time frame: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)
Proportion of Subjects With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at Final Treatment Visit.
Time frame: From baseline (day 1) to the final treatment visit (week 12 or week 24)
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IFN (Interferon, Peg-interferon alpha-2a or PEGASYS®) is available as a sterile, preservative-free, colorless to light yellow injectable solution administered subcutaneously. Each prefilled syringe of 180 μg/0.5 mL IFN (expressed as the amount of interferon alfa-2a) also contains acetic acid (0.0231 mg), benzyl alcohol (5 mg), polysorbate 80 (0.025 mg), sodium acetate trihydrate (1.3085 mg), and sodium chloride (4 mg) at pH 6 ± 0.5.
Change From Baseline in HCV RNA (log10 IU/mL)
Time frame: Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)