Clinical trial NCT03588923: Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of SH229 in Patients With HCV Infection
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HCV Infection
Keywords: HCV
NS5B
SH229
Lead sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-07-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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;

Primary outcomes:
measure: Incidence of adverse events
timeFrame: up to Day 10
measure: Antiviral effects of SH229, as measured by HCV RNA levels
timeFrame: up to Day 10
Secondary outcomes:
measure: Time to peak plasma concentration(Tmax)
timeFrame: up to Day 10
measure: Peak plasma concentration(Cmax)
timeFrame: up to Day 10
measure: Half-life time(t1/2)
timeFrame: up to Day 10
measure: Area under the plasma concentration versus time curve(AUC)
timeFrame: up to Day 10
Other outcomes:
Locations:
city: Changchun
country: China
facility: Phase I Clinical Trial Unit, The First Hospital of Jilin University
state: Jilin
Study officials:
affiliation: Phase I Clinical Trial Unit, The First Hospital of Jilin University
name: Yanhua Ding, MD
role: PRINCIPAL_INVESTIGATOR
References: