Tolerability, Efficacy, and PK of ZSP1601 in Patients With Non-Alcoholic Steatohepatitis (NASH)

A Multi-center, Randomized, Double-blind, Dose-increasing, Placebo-controlled，Multi-dose, 28-day Continuous Administration Phase Ib/IIa Clinical Trial to Evaluate the Tolerability, Efficacy, and PK of ZSP1601 in Patients With Nonalcoholic Steatohepatitis

Double-blind, randomized, placebo-controlled study to explore the safety, tolerability PK characteristics and early efficacy of ZSP1601 tablets in patients with non-alcoholic steatohepatitis (NASH).

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: ZSP1601; Drug: ZSP1601 Placebo

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • 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 required to meet the following criteria in order to be included in the trial:

  1. Signature signed informed consent before the trial, and fully understood the content, process and possible adverse reactions.
  2. Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.
  3. Subjects(including partners)have no gestation plans and must use reliable methods of contraception during the study and until 6 months following the last dose of investigational product.
  4. Male and female subjects aged 18-65 (including 18 and 65).
  5. B ultrasound confirmed fatty liver.
  6. NASH diagnosis or NASH phenotypic diagnosis.
  7. Liver fat ≥10% at baseline (MRI-PDFF)

Exclusion Criteria:

• Eligible subjects must not meet any of the following exclusion criteria:

  1. Excessive drinking for 3 consecutive months within 1 year before screening.
  2. Allergic constitution.
  3. Subjects who donated blood or bleeding profusely(> 400 mL)in the 3 months preceding study screening.
  4. Subjects having a history of bariatric surgery or preparing for bariatric surgery recently.
  5. Subjects having a history of liver transplantation or plans for liver transplantation
  6. Any diseases that increase the risk of bleeding, such as hemorrhoids, acute gastritis or gastric and duodenal ulcers.
  7. Liver biopsy indicates cirrhosis or previous clinical diagnosis of cirrhosis.
  8. Type 1 diabetes mellitus.
  9. Uncontrolled type 2 diabetes mellitus (HbA1c≥8.0%)。
  10. Any clinically significant abnormality upon physical examination or in the clinical laboratory tests, history or presence of other causes of liver disease,but not limited to above disorders: hepatitis b or hepatitis c virus (HCV) infection and chronic alcoholic liver disease, drug-induced liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson 's disease, alpha 1 - antitrypsin deficiency, liver, obvious abnormal liver function (ALT and AST acuity 5 x ULN or TBIL acuity 1.5 x ULN), etc.
  11. Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs.
  12. History of having any special food(including dragon fruit,mango,grapefruit,etc.),strenuous exercises,or other factors may interfere with the absorption, distribution, metabolism, or excretion of drug within 2 weeks prior to screening.
  13. Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
  14. Presence of clinically significant abnormalities in ECG or QTcB>450ms in males,or QTcB>470ms in females.
  15. HIV positive.
  16. Clinically significant nephropathy or renal dysfunction, blood creatinine >1.5×ULN, eGFR< 60 mL/min/1.73m2 [calculation formula: Ccr:(140-age)× weight (kg) /0.818×Scr(mumol /L), female ×0.85].
  17. Platelet count <100×109/L.
  18. Antinuclear antibody (ANA) confirmed positive and clinically significant.
  19. Abnormal TSH with clinical significance.
  20. Female during pregnancy and lactation or positive serum pregnancy test.
  21. Patients with contraindication of MRI scan.
  22. Take any product contains alcohol within 24 hours prior to dosing.
  23. Have chocolate, any food or beverage that contains caffeine or xanthine within 24 hours prior to dosing.
  24. Positive for urine drug screening or history of substance abuse for a period of 5 consecutive years before screening.
  25. Any acute illness or concomitant medication from screening to first dosing.
  26. As judged by the researcher, it is not suitable to join the clinical researcher.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: ZSP1601 Placebo; Subjects will receive matching placebo of ZSP1601
Experimental: ZSP1601-Dose 1; ZSP1601-50mg once daily	Drug: ZSP1601; ZSP1601 tablets be taken orally for 28 days.; Drug: ZSP1601 Placebo; Subjects will receive matching placebo of ZSP1601
Experimental: ZSP1601-Dose 2; ZSP1601-50mg twice daily	Drug: ZSP1601; ZSP1601 tablets be taken orally for 28 days.; Drug: ZSP1601 Placebo; Subjects will receive matching placebo of ZSP1601
Experimental: ZSP1601-Dose 3; ZSP1601-100mg once daily	Drug: ZSP1601; ZSP1601 tablets be taken orally for 28 days.; Drug: ZSP1601 Placebo; Subjects will receive matching placebo of ZSP1601

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE) following oral doses of ZSP1601 and placebo.	severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE)	Initiation of study treatment (Day 1) up to 2 weeks post-treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI-PDFF	liver fat content with Magnetic resonance imaging proton density fat fraction (MRI-PDFF)	Baseline and Day 28.
TNF-α	Tumor necrosis factor alpha level in serum	Baseline and Day 28.
ALT	serum Alanine Aminotransferase	Baseline and Day 28.
AST	serum Aspartate Aminotransferase	Baseline and Day 28.
Tmax	The time after dosing when Cmax occurs (Tmax)	Day1 and day 14
Cmax	Maximum Contentration	Day1 and day 14
t1/2z	t1/2z is defined as the time to decline half of the drug concentration in plasma.	Day1 and day 14
Rac of Cmax	Rac of ZSP1601 Peak Plasma Concentration at steady state	Day1 and day 14
DF of ZSP1601 at steady status	Multiple-dose plasma PK parameter: DF of ZSP1601 at steady status	Day1 and day 14
AUClast（AUC0-t）	AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.	Baseline (0h) and day 14
Rac of AUC	RAC of ZSP1601 Area under the plasma concentration versus time curve at steady state	Day1 and day 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(inf)	Area under the curve extrapolated until time is infinity (AUCinf)	Day1 and day 14

Collaborators and Investigators

• Sponsor: Guangdong Raynovent Biotech Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2020
• Primary Completion (Actual): August 3, 2021
• Study Completion (Actual): August 3, 2021

Study Registration Dates

• First Submitted: October 15, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 8, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ZSP1601-18-02

Drug and device information, study documents

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