Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of SH229 in Patients With HCV Infection

A Randomized, Double-blind, Placebo-controlled Phase I Study to Assess Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of SH229 in Patients With Hepatitis C Virus (HCV) Infection

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of single and multiple ascending doses of SH229 in patients with chronic hepatitis C Virus infection.

Study Overview

• Status: Completed
• Conditions: HCV Infection
• Intervention / Treatment: Drug: SH229; Drug: Placebos; Drug: SH229; Drug: SH229

Detailed Description

A total of 30 evaluable patients will be enrolled in this study. The planned dose levels are 400, 600, and 800 mg.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • Phase I Clinical Trial Unit, The First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects are willing to voluntarily take effective contraceptive measures from screening to 6 months after the last dose;
• 18-65 years of age;
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive, and a body weight ≥50 kg for males and ≥45 kg for females;
• No previous treatment with any direct-acting antiviral (DAA) drugs for HCV, such as Boceprevir, Telaprevir, Simeprevir, Sofosbuvir, Daclatasvir, Asunaprevir;
• No antiviral treatment such as immune modulators, thymosin or other immune stimulating factors, interferon, or Chinese herbs in the past 6 months;
• HCV RNA ≥10*5 IU/mL at screening (Roche COBAS Taqman);
• Chronic genotype 1-6 HCV Infection;
• Serum ALT ≤10 times ULN;
• FibroScan score ≤17.5kPa within 6 months before screening or at screening, or absence of cirrhosis within 12 months before screening;
• Subjects are capable of understanding and complying with the protocol and have signed the informed consent form.

Exclusion Criteria:

• Smoke more than 5 cigarettes per day within three months prior to screening;
• Subjects allergic to the study drug (including its excipients) or subjects who are prone to allergies;
• History of drug and/or alcohol abuse (alcohol consumption exceeding 14 units per week: 1 unit = 285 mL of beer, or 25 mL of hard liquor, or 100 mL of wine);
• Blood donation or massive blood loss (> 450 mL) within three months prior to screening;
• History of any non-HCV liver diseases, including but not limited to hemochromatosis, primary biliary cirrhosis, Wilson's disease, autoimmune hepatitis, drug or alcoholic hepatitis, non-alcoholic steatohepatitis, etc.;
• Subjects with dysphagia or with any gastrointestinal disorders (or postoperative conditions) that may affect the study drug absorption;
• Subjects with any diseases that increase the risk of bleeding, such as hemorrhoids, acute gastritis, or gastric and duodenal ulcers;
• Use of any drugs that alter liver enzyme activity within 28 days prior to screening;
• Use of any prescription drugs, over-the-counter drugs, vitamin products or herbal medicines within 14 days prior to screening;
• Use of special diet (including dragon fruit, mango, grapefruit, etc.), strenuous activities or other factors that may affect the disposition of the study drug within 2 weeks prior to screening;
• Concomitant use of strong inhibitors or inducers of CYP3A4, P-gp or Bcrp, such as itraconazole, ketoconazole or dronedarone;
• Subjects with major changes in diet or exercise habits recently;
• Participation in other clinical trials within three months prior to enrollment;
• Electrocardiogram abnormalities with clinical significance;
• Laboratory tests with clinical significance or other clinical findings that indicate clinically significant diseases not associated with HCV infection (including but not limited to gastrointestinal, renal, hepatic, neurologic, hematological, endocrine, pulmonary, psychiatric, cardiovascular diseases);
• Pregnant or lactating women;
• Creatinine clearance ≤ 60 mL/min;
• Evidence of co-infection with HBV, HIV, or syphilis;
• Child-Pugh Grade B or C;
• Clinically significant hepatic decompensation including but not limited to, hepatic encephalopathy, hepatocellular carcinoma, variceal bleeding, ascites, etc.;
• Use of chocolate, food or beverages containing caffeine or xanthine within 24 hours prior to dosing;
• Use of products containing alcohol within 24 hours prior to dosing;
• Subjects with urine drug screening test positive, or with history of drug abuse in the past 5 years;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1; SH229 (400 mg) or matching placebo, once daily	Drug: SH229; tablet, oral, 400 mg once daily for 3 days; Drug: Placebos; tablet, oral, once daily for 3 days; Drug: SH229; tablet, oral, 600 mg once daily for 3 days; Drug: SH229; tablet, oral, 800 mg once daily for 3 days
Active Comparator: Cohort 2; SH229 (600 mg) or matching placebo, once daily	Drug: SH229; tablet, oral, 400 mg once daily for 3 days; Drug: Placebos; tablet, oral, once daily for 3 days; Drug: SH229; tablet, oral, 600 mg once daily for 3 days; Drug: SH229; tablet, oral, 800 mg once daily for 3 days
Active Comparator: Cohort 3; SH229 (800 mg) or matching placebo, once daily	Drug: SH229; tablet, oral, 400 mg once daily for 3 days; Drug: Placebos; tablet, oral, once daily for 3 days; Drug: SH229; tablet, oral, 600 mg once daily for 3 days; Drug: SH229; tablet, oral, 800 mg once daily for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events	up to Day 10
Antiviral effects of SH229, as measured by HCV RNA levels	up to Day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to peak plasma concentration(Tmax)	up to Day 10
Peak plasma concentration(Cmax)	up to Day 10
Half-life time(t1/2)	up to Day 10
Area under the plasma concentration versus time curve(AUC)	up to Day 10

Collaborators and Investigators

• Sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.
• Investigators: Principal Investigator: Yanhua Ding, MD, Phase I Clinical Trial Unit, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2018
• Primary Completion (Actual): August 10, 2018
• Study Completion (Actual): August 10, 2018

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 15, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Actual): August 28, 2018
• Last Update Submitted That Met QC Criteria: August 24, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: NS5B; HCV; SH229
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Infections; Communicable Diseases; Hepatitis C
• Other Study ID Numbers: SHC005-I-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No