Clinical trial NCT04140123: Tolerability, Efficacy, and PK of ZSP1601 in Patients With Non-Alcoholic Steatohepatitis (NASH)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Alcoholic Steatohepatitis (NASH)
Lead sponsor: Guangdong Raynovent Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2019-10-25
Enrollment: 37
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: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE) following oral doses of ZSP1601 and placebo.
timeFrame: Initiation of study treatment (Day 1) up to 2 weeks post-treatment.
Secondary outcomes:
measure: MRI-PDFF
timeFrame: Baseline and Day 28.
measure: TNF-α
timeFrame: Baseline and Day 28.
measure: ALT
timeFrame: Baseline and Day 28.
measure: AST
timeFrame: Baseline and Day 28.
measure: Tmax
timeFrame: Day1 and day 14
measure: Cmax
timeFrame: Day1 and day 14
measure: t1/2z
timeFrame: Day1 and day 14
measure: Rac of Cmax
timeFrame: Day1 and day 14
measure: DF of ZSP1601 at steady status
timeFrame: Day1 and day 14
measure: AUClast（AUC0-t）
timeFrame: Baseline (0h) and day 14
measure: Rac of AUC
timeFrame: Day1 and day 14
Other outcomes:
measure: AUC(inf)
timeFrame: Day1 and day 14
Locations:
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
Study officials:
References: