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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.
Full description
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:
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Inclusion criteria
(1) A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit or (2) A liver biopsy or FibroTest performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection, such as the presence of fibrosis and/or inflammation.
Positive for anti-HCV antibody at Screening. 6. Presence of an HCV RNA level ≥ 1 x 10000 IU/mL at Screening as determined by the Central Laboratory.
Presence of genotype 1b HCV-infection at Screening as determined by the Central Laboratory. Any non-definitive results will exclude the subject from study participation.
HCV treatment naïve defined as no prior therapy with any interferon (IFN), ribavirin (RBV), or other approved or investigational HCV-specific agent.
Absence of cirrhosis
Cirrhosis as defined as any one of the following:
If no definitive diagnosis of cirrhosis by the above criteria, a liver biopsy is required; liver biopsy results will supersede non-invasive testing results and be considered definitive.
Screening ECG without clinically significant abnormalities. 11. Subjects must have the following laboratory parameters at Screening:
ALT ≤ 10 × the upper limit of normal (ULN)
AST ≤ 10 × ULN
Total bilirubin ≤ 1.5 × ULN except history of Gilbert's syndrome. If Gilbert's syndrome is the proposed etiology, the total bilirubin must ≤ 2 × ULN.
Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
Platelet count ≥ 90,000 cells/mm3
HbA1c ≤ 8.5%
Thyroid stimulating hormone (TSH) and free T4 ≤ ULN
Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault equation
Serum creatinine ≤ 1.5 × ULN
Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects
Albumin ≥ 3.5 g/dL
INR (International Normalized Ratio for Prothrombin Time) ≤ 1.5 x ULN unless subject is stable on an anticoagulant regimen affecting INR
Anti-nuclear antibodies (ANA) ≤ 1:320. 12. Subject must be of generally good health, with the exception of chronic HCV infection, as determined by Investigator.
Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments, including all required Post-Treatment visits.
A female subject is eligible to enter the study if it is confirmed that she is:
(1) Not pregnant or nursing. (2) Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal - women > 50 years of age with cessation (for ≥12 months) of previously occurring menses), or (3) Of childbearing potential (i.e., women who have not had a hysterectomy, have not had both ovaries removed, and have not had medically documented ovarian failure).
Women ≤ 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at the Baseline/Day 1 visit prior to randomization. They must also agree to one of the following from Screening until 6 months after the last dose of study drug(s):
Or - Consistent and correct use of 1 of the following methods of birth control listed below, in addition to a male partner who correctly uses a condom, from Screening until 6 months after the last dose of study drug(s):
i. implants of levonorgestrel ii. injectable progesterone iii. oral contraceptives (either combined or progesterone only) iv. contraceptive vaginal ring v. transdermal contraceptive patch. 15. Male subjects must agree to consistently and correctly use a condom, while their female partner agrees to use 1 of the methods of birth control listed above, from Screening until 6 months after the last dose of study drug(s).
Exclusion criteria
(1) Hematologic stimulating agents (e.g., erythropoiesis-stimulating agents [ESAs], granulocyte colony stimulating factor [G-CSF], and thrombopoietin [TPO] mimetics) (2) Chronic use of systemic immunosuppressants including, but not limited to, corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks), azathioprine, or monoclonal antibodies (eg, infliximab) (3) Investigational agents or devices for any indication (4) Drugs disallowed per prescribing information of RBV or IFN (5) Any prohibited medications listed in Table 6-2. 11. Known hypersensitivity to RBV, IFN, TG-2349, sulfa drugs, or formulation excipients.
Current or prior history of any of the following:
Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded.
Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drugs.
Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).
Central nervous system (CNS) trauma, seizure disorder, stroke or transient ischemic attack.
Solid organ transplantation.
Significant cardiac disease (including but not limited to the myocardial infarction based on ECG and/or clinical history).
Significant pulmonary disease or porphyria.
Clinically significant retinal disease
Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 12 months prior to Baseline/Day 1 or has not required medication in the last 12 months may be included.
Malignancy within 5 years prior to Screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible.
Significant drug allergy (such as anaphylaxis or hepatotoxicity).
Primary purpose
Allocation
Interventional model
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25 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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