SH229 Tablets Combined With Daclatasvir Dihydrochloride Tablets in Treatment Adult Patients With Chronic Hepatitis C

NCT04070235 | Unknown Phase 2 DMC

• 1 other identifier: SHC005-II/III-01
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II: Exploring the efficacy and safety of different doses of SH229 tablets combined with fixed-dose Daclatasvi dihydrochloride (DCV) tablets in the treatment of adult patients with chronic hepatitis C for 12 weeks, providing a basis for the design and implementation of phase III clinical trials. Phase III: Confirmation of the efficacy and safety of SH229 tablets combined with Daclatasvi dihydrochloride (DCV) tablets in the treatment of adult patients with chronic hepatitis C for 12 weeks, providing a sufficient basis for drug registration and clinical use.

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C virus; SH229

Outcome Measures

Primary Outcomes (1)

• Sustained virologic response at 12 weeks after end of treatment (SVR12)

  Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  12 weeks after end of treatment

Secondary Outcomes (7)

• Rapid virologic response at 4 week after initiation of treatment (RVR4)

  4 week after initiation of treatment

• Rapid virologic response at 12 weeks after initiation of treatment (RVR12)

  12 weeks after initiation of treatment

• Sustained virologic response at 4 weeks after end of treatment (SVR4)

  4 weeks after end of treatment

• Sustained virologic response at 24 weeks after end of treatment (SVR24)

  24 weeks after end of treatment

• Virologic breakthrough

  2, 4, 8 and 12 weeks after initiation of treatment

Study Arms (4)

SH229/DCV 400mg/60mg

EXPERIMENTAL

HCV GT 1-6 participants were medicated with SH229 tablets 400 mg once daily and DCV tablets 60 mg once daily QD (n=40) for 12weeks

Drug: SH229 tablets; Drug: Daclatasvir dihydrochloride

SH229/DCV 600mg/60mg

EXPERIMENTAL

HCV GT 1-6 participants were medicated with SH229 tablets 600 mg once daily and DCV tablets 60 mg once daily (n=40).

Drug: SH229 tablets; Drug: Daclatasvir dihydrochloride

SH229/DCV 800mg/60mg

EXPERIMENTAL

HCV GT 1-6 participants were medicated with SH229 tablets 800 mg once daily and DCV tablets 60 mg once daily (n=40).

Drug: SH229 tablets; Drug: Daclatasvir dihydrochloride

SH229/DCV

EXPERIMENTAL

HCV GT 1-6 participants were medicated with SH229 tablets 400 mg,600 mg or 800 mg once daily and DCV tablets 60 mg once daily

Drug: SH229 tablets; Drug: Daclatasvir dihydrochloride

Interventions

SH229 tablets DRUG

SH229 400 mg was provided in 4 tablets, 100mg each；SH229 600 mg was provided in 6 tablets , 100mg each；SH229 800 mg in was provided in 8tablets , 100mg each。

Also known as: Holybuvir

SH229/DCV; SH229/DCV 400mg/60mg; SH229/DCV 600mg/60mg; SH229/DCV 800mg/60mg

Daclatasvir dihydrochloride DRUG

Daclatasvir dihydrochloride was provided in a single tablet of 60 mg.

Also known as: DAKLINZA

SH229/DCV; SH229/DCV 400mg/60mg; SH229/DCV 600mg/60mg; SH229/DCV 800mg/60mg

Eligibility Criteria

• Age: 18 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.
• Subjects should be able to follow the instructions for the study drug and be able to complete screening, on-treatment, and post treatment assessments.
• Male or female, age above 18 years
• Body mass index ( BMI ) between 18 and 32 kg/m2 at Screening.
• Confirmation of chronic HCV infection, which meets one of the following: (a) positive for anti-HCV antibodies, HCV RNA or HCV genotyping results within ≤ 6 months of screening, or (b) liver biopsy ≤ 12 months of screening.
• HCV RNA above 10\^4 IU/mL at Screening by the Central Laboratory.
• HCV genotype 1, 2, 4, 5, 6, or indeterminate assessed at Screening by the Central Laboratory.
• Classification as treatment naïve or treatment experienced (approximately 20% of subjects may be treatment experienced):
• Treatment naïve is defined as having never been exposed to approved or experimental HCV-specific direct-acting antiviral agents ( DAA ) or prior treatment of HCV with interferon either with or without RBV.
• Treatment experienced is defined as prior treatment failure to a regimen containing IFN-based antiviral (INF-α, β or PEG-IFN ± ribavirin) and met one of the following: (i) Non-Responder: Subject did not achieve undetectable HCV RNA levels while ontreatment,, (ii) Relapse/Breakthrough: Subject achieved undetectable HCV RNA levels duringtreatment but did not achieve SVR, (iii) Terminate the treatment , according to associated-HCV therapy adverse events by subject reported or medical records demonstrated.
• Cirrhosis Determination (approximately 20% of subjects may have cirrhosis)：
• Cirrhosis is defined as any one of the following: (i) Fibroscan with a result of \>12.5 kPa within ≤ 6 months of screening, (ii) Liver biopsy showing cirrhosis within ≤ 12 months of screening.
• Absence of cirrhosis is defined as any one of the following:(i) Fibroscan with a result of ≤ 12.5 kPa within ≤ 6 months of screening, (ii) Liver biopsy showing non-cirrhosis within ≤ 12 months of screening.

You may not qualify if:

• Exposure nucleotide analogue including HCV NS3-4A inhibitor, HCV NS5B inhibitor or any HCV NS5A inhibitor before baseline/Day 1.
• Receive IFN-based antiviral therapy within 6 months prior to baseline/day 1.
• Oral or injection of RBV within 3 months prior to baseline/Day 1.
• Systemic use of potent immunomodulators (eg, adrenocortical hormone, thymosin alpha, etc.) for more than 2 weeks prior to baseline/day 1, or expected to be exposed to these agents during the study.
• Use of amiodarone within 2 months before baseline/day 1.
• Positive for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) at screening.
• Evidence of decompensatory liver function, including but not limited to total serum bilirubin (TBIL) above twice of the upper limit of normal (ULN), serum albumin (ALB) below 35 g/L or prothrombin activity (PTA) below 60% confirmed on repeated testing, previous or present history of ascites, upper gastrointestinal bleeding and/or hepatic encephalopathy, or with a liver function reserve of Child-Pugh class B or C.
• Primary liver cancer confirmed or evidenced by serum alfa-fetoprotein (AFP) above 100 ng/ml or liver imaging study showing suspected nodules.
• liver disease of a non-HCV etiology (e.g. alcoholic liver disease, nonalcoholic steatohepatitis, drug-induced hepatitis, autoimmune hepatitis, Wilson disease or hemochromatosis, etc.).
• Subjects has the following laboratory parameters at screening: ALT or AST\>10×ULN, WBC \< 3×109 /L, ANC\< 1.5×109 /L（or \< 1.25×109 /L for cirrhotics ), PLT\< 50×109 /L, Hb \< 100 g/L, INR \> 1.5×ULN, CLcr \< 50 mL/min（calculated by the Cockcroft-Gault equation ）.
• Uncontrolled diabetes mellitus (HbA1c \> 8.0% at screening).
• Uncontrolled hyperthyroidism or diminished.
• Psychiatric or neurologic disorders, including previous or family history of psychiatric disorders (especially depression, depressive state, epilepsy or hysteria).
• Serious cardiovascular disorders, including uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥100 mmHg), heart insufficiency of New York Heart Association class III or above, history of myocardial infarction within 6 months before the screening, history of percutaneous transluminal coronary angioplasty within 6 months before the screening, unstable angina pectoris, or QTc interval (Fridericia correction formula QTc = QT×RR\^-1/3) at or above 450 mse, second- or third-grade atrioventricular block or any other uncontrolled arrhythmias confirmed on repeated electrocardiography on screening.
• Serious hematologic disorders (e.g. anemia, hemophilia, etc.).

Sponsors & Collaborators

• Nanjing Sanhome Pharmaceutical, Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Jilin, Jiangsu, 130021, China

Location

Related Publications (2)

• Hua R, Kong F, Li G, Wen X, Zhang Y, Yang X, Meng C, Xie W, Jiang Y, Wang X, Han X, Huang Y, Mao Q, Wang J, Guan Y, Chen J, Ma Y, Xiong Q, Ma H, Yan X, Rao H, Zhao Y, Sun T, Zhu L, Mao X, Lian J, Deng G, Xin Y, Wang Y, Ye Y, Xu B, Gao H, Tan Y, Li D, Yang D, Su M, Zhang X, Min J, Shi X, Wei L, Niu J. Alfosbuvir plus Daclatasvir for Treatment of Chronic Hepatitis C Virus Infection in China. Infect Dis Ther. 2023 Nov;12(11):2595-2609. doi: 10.1007/s40121-023-00872-4. Epub 2023 Oct 19.

  PMID: 37856013 DERIVED

• Hua R, Kong F, Wen X, Xiong Q, Chen J, Meng C, Ma H, Tan Y, Huang Y, Jiang Y, Guan Y, Mao X, Wang J, Xin Y, Gao H, Xu B, Li C, Wu Q, Zhang X, Wang Z, Zhao L, Zhang Y, Li G, Niu J. Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open-label, phase 2 study. J Viral Hepat. 2022 Jun;29(6):455-464. doi: 10.1111/jvh.13650. Epub 2022 Apr 8.

  PMID: 35080256 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

daclatasvir

Condition Hierarchy (Ancestors)

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

Study Officials

• Junqi Niu, Ph.D

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Phase 2 is parallel;Phase 3 is single group

Study Record Dates

• First Submitted: August 11, 2019
• First Posted: August 28, 2019
• Study Start: March 29, 2019
• Primary Completion: December 1, 2019
• Study Completion: August 1, 2020
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)