A Study to Evaluate the Efficacy and Safety of TG-2349 in Combination With Peg-interferon and Ribavirin in Subjects With Chronic Hepatitis C Virus Genotype 1b Infection

• Sponsor: TaiGen Biotechnology Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02340962
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arms: 2
• Duration (Months): 17.9
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: TG-2349; Drug: Ribavirin; Drug: Interferon Alfa-2a	Phase 2

Detailed 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:

• 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 Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Aug 12, 2016
• Actual Study Completion Date: Oct 26, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I 200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	Drug: TG-2349; 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.; Drug: Ribavirin; 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.; Drug: Interferon Alfa-2a; 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.
Experimental: Group II 400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin	Drug: TG-2349; 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.; Drug: Ribavirin; 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.; Drug: Interferon Alfa-2a; 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.

Outcome Measures

Primary Outcome Measures

1. Antiviral Efficacy is Measured by the 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. [12 weeks after the end of treatment (SVR12), after 12 to 24 weeks treatments]

   Antiviral efficacy is measured by the 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.

Secondary Outcome Measures

1. Proportion of Subjects Achieving Sustained Viral Response at 4, 8, and 24 Weeks After the End of Treatment (SVR4, SVR8, and SVR24) [4, 8, 24 weeks after the end of treatment (SVR4, 8, 24), after 12 to 24 weeks treatments]

2. Proportion of Subjects Achieving HCV RNA < Lower Limit of Quantification, Target Detected or Target Not Detected (< LLOQ, TD or TND) [The whole treatment period, 12 to 24 weeks]

3. Proportion of Subjects Achieving HCV RNA < LLOQ, TND [Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)]

4. Mean Absolute Values in HCV RNA (log10 IU/mL) [Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)]

5. Proportion of Subjects Experiencing Virologic Failure During Treatment and Viral Relapse After the End of Treatment. [Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)]

6. Proportion of Subjects With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at Final Treatment Visit. [From baseline (day 1) to the final treatment visit (week 12 or week 24)]

7. Change From Baseline in HCV RNA (log10 IU/mL) [Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Willing and able to provide written informed consent.

2. East Asian subjects, male or female, and age between 18 (or legal adult age) and 70 years, inclusive, at Baseline/Day 1.

3. Body mass index (BMI) in the range of 18.0 to 35.0 kg/m2 (inclusive) and body weight ≥ 40 kg.

4. Presence of chronic hepatitis C (CHC) as documented below:

(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.

1. 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.

2. 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.

3. HCV treatment naïve defined as no prior therapy with any interferon (IFN), ribavirin (RBV), or other approved or investigational HCV-specific agent.

4. Absence of cirrhosis

Cirrhosis as defined as any one of the following:

1. Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥ 5).

2. FibroScan showing cirrhosis or results > 12.5 kPa.

3. FibroTest fibrosis score of > 0.58 and APRI (AST: platelet ratio index) of > 2 during Screening.

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.

1. Screening ECG without clinically significant abnormalities. 11. Subjects must have the following laboratory parameters at Screening:

2. ALT ≤ 10 × the upper limit of normal (ULN)

3. AST ≤ 10 × ULN

4. 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.

5. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

6. Platelet count ≥ 90,000 cells/mm3

7. HbA1c ≤ 8.5%

8. Thyroid stimulating hormone (TSH) and free T4 ≤ ULN

9. Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault equation

10. Serum creatinine ≤ 1.5 × ULN

11. Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects

12. Albumin ≥ 3.5 g/dL

13. INR (International Normalized Ratio for Prothrombin Time) ≤ 1.5 x ULN unless subject is stable on an anticoagulant regimen affecting INR

14. 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.

15. 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.

16. 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):

• Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not permitted.

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):

1. intrauterine device (IUD) with a failure rate of < 1% per year

2. female barrier method: cervical cap or diaphragm with spermicidal agent

3. tubal sterilization

4. vasectomy in male partner

5. hormone-containing contraceptive:

1. 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).

1. Male subjects must agree to refrain from sperm donation from Screening until at least 6 months after the last dose of study drug(s).

Exclusion Criteria:

1. Presence of cirrhosis.

2. Positive serological test for IgM anti-HAV (hepatitis A virus) antibody or HBsAg at Screening.

3. Positive ELISA test for HIV-1 or HIV-2 at Screening.

4. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson disease, alfa-1 antitrypsin deficiency, cholangitis).

5. Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1.

6. Clinically-relevant drug abuse within 12 months of Screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by Investigator.

7. Alcohol misuse as defined by an AUDIT score of ≥ 8.

8. Contraindications to RBV or IFN therapy, including hemoglobinopathies (e.g., thalassemia major or sickle-cell anemia), autoimmune thyroiditis or other autoimmune disorders including autoimmune hepatitis.

9. Pregnant or nursing female or male with pregnant female partner.

10. Use of any prohibited medications within 30 days of the Baseline/Day 1 visit:

(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.

1. Current or prior history of any of the following:

2. 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.

3. Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drugs.

4. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.

5. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).

6. Central nervous system (CNS) trauma, seizure disorder, stroke or transient ischemic attack.

7. Solid organ transplantation.

8. Significant cardiac disease (including but not limited to the myocardial infarction based on ECG and/or clinical history).

9. Significant pulmonary disease or porphyria.

10. Clinically significant retinal disease

11. 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.

12. 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.

13. Significant drug allergy (such as anaphylaxis or hepatotoxicity).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan

Sponsors and Collaborators

• TaiGen Biotechnology Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: TaiGen Biotechnology Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02340962
• Other Study ID Numbers: TG-2349-03
• First Posted: Jan 19, 2015
• Last Update Posted: Oct 12, 2018
• Last Verified: Sep 1, 2018

• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2

Study Results

Participant Flow

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Period Title: Overall Study
STARTED	13	12
COMPLETED	12	12
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Group I	Group II	Total
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin	Total of all reporting groups
Overall Participants	13	12	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.8 (10.76)	54.0 (11.91)	52.3 (11.21)
Sex: Female, Male (Count of Participants)
Female	8 61.5%	5 41.7%	13 52%
Male	5 38.5%	7 58.3%	12 48%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	13 100%	12 100%	25 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	62.8 (13.69)	64.0 (9.11)	63.4 (11.49)

Outcome Measures

1. Primary Outcome

Title	Antiviral Efficacy is Measured by the 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.
Description	Antiviral efficacy is measured by the 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 to 24 weeks treatments

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
Count of Participants [Participants]	11 84.6%	10 83.3%

2. Secondary Outcome

Title	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 to 24 weeks treatments

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
SVR4	12 92.3%	10 83.3%
SVR8	11 84.6%	10 83.3%
SVR24	11 84.6%	10 83.3%

3. Secondary Outcome

Title	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 to 24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs. Missing data were excluded in the dominator of on-treatment visits.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
Baseline	0 0%	0 0%
Day 4	1 7.7%	0 0%
Week 1	3 23.1%	4 33.3%
Day 10	6 46.2%	8 66.7%
Week 2	9 69.2%	10 83.3%
Week 3	11 84.6%	10 83.3%
Week 4	12 92.3%	11 91.7%
Week 6	11 84.6%	11 91.7%
Week 8	11 84.6%	11 91.7%
Week 10	11 84.6%	11 91.7%
Week 12	11 84.6%	11 91.7%

4. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs. Missing data were excluded in the dominator of on-treatment visits, while imputation was performed at post-treatment visits and the dominator for post-treatment visits was the total population.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
Baseline	0 0%	0 0%
Day 4	0 0%	0 0%
Week 1	1 7.7%	1 8.3%
Day 10	0 0%	3 25%
Week 2	2 15.4%	4 33.3%
Week 3	4 30.8%	9 75%
Week 4	6 46.2%	9 75%
Week 6	7 53.8%	10 83.3%
Week 8	11 84.6%	10 83.3%
Week 10	9 69.2%	11 91.7%
Week 12	11 84.6%	10 83.3%
Post-Treatment Week 4	12 92.3%	10 83.3%
Post-Treatment Week 8	11 84.6%	10 83.3%
Post-Treatment Week 12	11 84.6%	9 75%
Post-Treatment Week 24	10 76.9%	10 83.3%

5. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
Baseline	5.8 (0.83)	5.9 (0.66)
Day 4	1.9 (0.40)	2.0 (0.74)
Week 1	1.4 (0.52)	1.4 (0.54)
Day 10	1.2 (0.19)	1.1 (0.83)
Week 2	1.0 (0.48)	1.0 (0.72)
Week 3	0.7 (0.51)	0.4 (0.78)
Week 4	0.5 (0.54)	0.4 (0.71)
Week 6	0.4 (0.53)	0.1 (0.31)
Week 8	0.0 (0.00)	0.1 (0.31)
Week 10	0.2 (0.42)	0.0 (0.00)
Week 12	0.0 (0.00)	0.1 (0.31)
Post-Treatment Week 4	0.0 (0.00)	0.8 (1.79)
Post-Treatment Week 8	0.2 (0.57)	0.9 (2.13)
Post-Treatment Week 12	0.5 (1.86)	1.0 (2.22)
Post-Treatment Week 24	0.1 (0.31)	0.0 (0.00)

6. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
Virologic failure	1 7.7%	2 16.7%
On-Treatment failure	0 0%	1 8.3%
Post-Treatment relapse	1 7.7%	1 8.3%

7. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
ALT > ULN at baseline	7 53.8%	7 58.3%
ALT normalization	2 15.4%	5 41.7%

8. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

Arm/Group Title	Group I	Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin	400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
Measure Participants	13	12
Day 4	-3.8 (0.51)	-3.9 (0.55)
Week 1	-4.4 (0.50)	-4.5 (0.56)
Day 10	-4.6 (0.75)	-4.8 (0.78)
Week 2	-4.8 (0.91)	-4.9 (1.01)
Week 3	-5.0 (1.03)	-5.5 (0.96)
Week 4	-5.2 (0.79)	-5.5 (0.73)
Week 6	-5.4 (0.86)	-5.7 (0.65)
Week 8	-5.8 (0.90)	-5.7 (0.70)
Week 10	-5.6 (0.86)	-5.8 (0.67)
Week 12	-5.8 (0.90)	-5.7 (0.68)
Post-Treatment Week 4	-5.8 (0.86)	-5.1 (1.72)
Post-Treatment Week 8	-5.6 (0.88)	-5.0 (2.05)
Post-Treatment Week 12	-5.2 (1.81)	-4.8 (2.10)
Post-Treatment Week 24	-5.6 (0.83)	-5.8 (0.70)

Adverse Events

Time Frame	Adverse event that occurred after the first dose of study drugs and no later than the date subject completed/withdrawed from the study will be collected and analyzed.
Arm/Group Title	Group I		Group II
Arm/Group Description	200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin		400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin
All Cause Mortality
	Group I		Group II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Serious Adverse Events
	Group I		Group II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		2/12 (16.7%)
Blood and lymphatic system disorders
Neutropenia	1/13 (7.7%)	1	0/12 (0%)	0
Infections and infestations
Cellulitis	1/13 (7.7%)	1	0/12 (0%)	0
Injury, poisoning and procedural complications
Lower limb fracture	0/13 (0%)	0	1/12 (8.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/13 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Group I		Group II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		12/12 (100%)
Blood and lymphatic system disorders
Anaemia	5/13 (38.5%)	5	6/12 (50%)	7
Neutropenia	6/13 (46.2%)	7	3/12 (25%)	3
Leukopenia	4/13 (30.8%)	6	2/12 (16.7%)	3
Ear and labyrinth disorders
Vertigo	1/13 (7.7%)	1	0/12 (0%)	0
Endocrine disorders
Hyperthyroidism	0/13 (0%)	0	1/12 (8.3%)	1
Eye disorders
Dry eye	1/13 (7.7%)	1	1/12 (8.3%)	1
Gastrointestinal disorders
Mouth ulceration	3/13 (23.1%)	3	3/12 (25%)	4
Nausea	3/13 (23.1%)	4	1/12 (8.3%)	1
Abdominal distension	1/13 (7.7%)	1	1/12 (8.3%)	1
Diarrhoea	1/13 (7.7%)	1	1/12 (8.3%)	1
Dry mouth	1/13 (7.7%)	1	1/12 (8.3%)	1
Faeces soft	1/13 (7.7%)	1	0/12 (0%)	0
Abdominal pain	1/13 (7.7%)	1	0/12 (0%)	0
Abdominal pain upper	1/13 (7.7%)	1	0/12 (0%)	0
Toothache	1/13 (7.7%)	1	0/12 (0%)	0
Vomiting	1/13 (7.7%)	1	0/12 (0%)	0
General disorders
Pain	5/13 (38.5%)	5	5/12 (41.7%)	6
Pyrexia	2/13 (15.4%)	2	4/12 (33.3%)	5
Chest discomfort	2/13 (15.4%)	2	1/12 (8.3%)	1
Fatigue	1/13 (7.7%)	1	2/12 (16.7%)	2
Chest pain	1/13 (7.7%)	1	1/12 (8.3%)	1
Feeling cold	1/13 (7.7%)	2	1/12 (8.3%)	1
Asthenia	1/13 (7.7%)	1	0/12 (0%)	0
Injection site erythema	0/13 (0%)	0	1/12 (8.3%)	1
Injection site rash	1/13 (7.7%)	1	0/12 (0%)	0
Local swelling	1/13 (7.7%)	2	0/12 (0%)	0
Malaise	0/13 (0%)	0	1/12 (8.3%)	1
Thirst	1/13 (7.7%)	1	0/12 (0%)	0
Infections and infestations
Cellulitis	0/13 (0%)	0	1/12 (8.3%)	1
Upper respiratory tract infection	1/13 (7.7%)	1	1/12 (8.3%)	1
Folliculitis	1/13 (7.7%)	1	0/12 (0%)	0
Gingivitis	0/13 (0%)	0	1/12 (8.3%)	1
Infected dermal cyst	0/13 (0%)	0	1/12 (8.3%)	1
Nasopharyngitis	1/13 (7.7%)	1	0/12 (0%)	0
Otitis media	0/13 (0%)	0	1/12 (8.3%)	1
Pyuria	1/13 (7.7%)	1	0/12 (0%)	0
Tonsillitis	1/13 (7.7%)	1	0/12 (0%)	0
Injury, poisoning and procedural complications
Contusion	1/13 (7.7%)	1	0/12 (0%)	0
Limb injury	0/13 (0%)	0	1/12 (8.3%)	1
Road traffic accident	1/13 (7.7%)	1	0/12 (0%)	0
Wound	1/13 (7.7%)	1	0/12 (0%)	0
Investigations
Blood bilirubin increased	1/13 (7.7%)	1	1/12 (8.3%)	1
Alanine aminotransferase increased	1/13 (7.7%)	1	0/12 (0%)	0
Aspartate aminotransferase increased	1/13 (7.7%)	1	0/12 (0%)	0
Blood creatine phosphokinase increased	1/13 (7.7%)	1	0/12 (0%)	0
Gamma-glutamyltransferase increased	1/13 (7.7%)	1	0/12 (0%)	0
Platelet count decreased	0/13 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
Decreased appetite	3/13 (23.1%)	3	3/12 (25%)	3
Musculoskeletal and connective tissue disorders	2/13 (15.4%)	2	1/12 (8.3%)	1
Back pain	2/13 (15.4%)	2	0/12 (0%)	0
Plantar fasciitis	0/13 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
Dizziness	4/13 (30.8%)	6	4/12 (33.3%)	4
Headache	4/13 (30.8%)	7	3/12 (25%)	3
Memory impairment	2/13 (15.4%)	2	1/12 (8.3%)	1
Dysgeusia	0/13 (0%)	0	1/12 (8.3%)	1
Psychiatric disorders
Insomnia	4/13 (30.8%)	4	1/12 (8.3%)	1
Anxiety	1/13 (7.7%)	1	1/12 (8.3%)	2
Attention deficit/hyperactivity disorder	1/13 (7.7%)	1	1/12 (8.3%)	2
Depression	0/13 (0%)	0	1/12 (8.3%)	1
Irritability	1/13 (7.7%)	1	0/12 (0%)	0
Sleep disorder	0/13 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/13 (15.4%)	2	3/12 (25%)	3
Dyspnoea	1/13 (7.7%)	1	0/12 (0%)	0
Epistaxis	0/13 (0%)	0	1/12 (8.3%)	1
Oropharyngeal pain	0/13 (0%)	0	1/12 (8.3%)	1
Productive cough	1/13 (7.7%)	1	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	4/13 (30.8%)	4	5/12 (41.7%)	6
Alopecia	3/13 (23.1%)	3	2/12 (16.7%)	2
Rash	1/13 (7.7%)	1	2/12 (16.7%)	2
Dry skin	1/13 (7.7%)	1	1/12 (8.3%)	1
Eczema	1/13 (7.7%)	1	0/12 (0%)	0
Papule	1/13 (7.7%)	1	0/12 (0%)	0
Rash pruritic	1/13 (7.7%)	1	0/12 (0%)	0
Seborrhoeic dermatitis	0/13 (0%)	0	1/12 (8.3%)	1
Vesicle	0/13 (0%)	0	1/12 (8.3%)	1
Vascular disorders
Hypertension	1/13 (7.7%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.