Evaluate the Efficacy and Safety of TG-2349 in Subjects With Hepatitis C Infection

NCT02340962 | Completed Phase 2 Results DMC

• 1 other identifier: TG-2349-03
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks after the end of treatment (SVR12), after 12-week treatments

Secondary Outcomes (7)

• 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-week treatments

• 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 weeks

• Proportion of Subjects Achieving HCV RNA < LLOQ, TND

  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)

  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.

  Treatment period (12 to 24 weeks) and after the end of treatment (12 to 24 weeks)

Study Arms (2)

Group I

EXPERIMENTAL

200 mg TG-2349 (2 capsules) + Interferon or Peg-interferon + Ribavirin

Drug: TG-2349; Drug: Ribavirin; Drug: Interferon Alfa-2a

Group II

EXPERIMENTAL

400 mg TG-2349 (4 capsules) + Interferon or Peg-interferon + Ribavirin

Drug: TG-2349; Drug: Ribavirin; Drug: Interferon Alfa-2a

Interventions

TG-2349 DRUG

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.

Group I; Group II

Ribavirin DRUG

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.

Group I; Group II

Interferon Alfa-2a DRUG

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.

Group I; Group II

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• East Asian subjects, male or female, and age between 18 (or legal adult age) and 70 years, inclusive, at Baseline/Day 1.
• Body mass index (BMI) in the range of 18.0 to 35.0 kg/m2 (inclusive) and body weight ≥ 40 kg.
• 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.
• \. 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:
• Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥ 5).
• FibroScan showing cirrhosis or results \> 12.5 kPa.
• 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.
• \. Screening ECG without clinically significant abnormalities. 11. Subjects must have the following laboratory parameters at Screening:

You may not qualify if:

• Presence of cirrhosis.
• Positive serological test for IgM anti-HAV (hepatitis A virus) antibody or HBsAg at Screening.
• Positive ELISA test for HIV-1 or HIV-2 at Screening.
• Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson disease, alfa-1 antitrypsin deficiency, cholangitis).
• Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1.
• 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.
• Alcohol misuse as defined by an AUDIT score of ≥ 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.
• Pregnant or nursing female or male with pregnant female partner.
• 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.
• \. 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.

Sponsors & Collaborators

• TaiGen Biotechnology Co., Ltd.: lead

Study Sites (1)

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Ribavirin; Interferon alpha-2

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Li-Wen Chang
• Organization: TaiGen Biotechnology Co., Ltd.

lwchang@taigenbiotech.com

+886-2-8177-7020

Study Officials

• Ming-Lung Yu

  Kaohsiung Medical University Chung-Ho Memorial Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2015
• First Posted: January 19, 2015
• Study Start: May 1, 2015
• Primary Completion: August 12, 2016
• Study Completion: October 26, 2016
• Last Updated: July 14, 2023
• Results First Posted: October 12, 2018

Record last verified: 2018-09

Locations

TW (1)