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

NCT04140123 | Completed Phase 1

• 1 other identifier: ZSP1601-18-02
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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).

Conditions

Non-Alcoholic Steatohepatitis (NASH)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• MRI-PDFF

  Baseline and Day 28.

• TNF-α

  Baseline and Day 28.

• ALT

  Baseline and Day 28.

• AST

  Baseline and Day 28.

• Tmax

  Day1 and day 14

Other Outcomes (1)

• AUC(inf)

  Day1 and day 14

Study Arms (4)

ZSP1601-Dose 1

EXPERIMENTAL

ZSP1601-50mg once daily

Drug: ZSP1601; Drug: ZSP1601 Placebo

ZSP1601-Dose 2

EXPERIMENTAL

ZSP1601-50mg twice daily

Drug: ZSP1601; Drug: ZSP1601 Placebo

ZSP1601-Dose 3

EXPERIMENTAL

ZSP1601-100mg once daily

Drug: ZSP1601; Drug: ZSP1601 Placebo

Placebo

PLACEBO COMPARATOR

Placebo

Drug: ZSP1601 Placebo

Interventions

ZSP1601 DRUG

ZSP1601 tablets be taken orally for 28 days.

ZSP1601-Dose 1; ZSP1601-Dose 2; ZSP1601-Dose 3

ZSP1601 Placebo DRUG

Subjects will receive matching placebo of ZSP1601

Placebo; ZSP1601-Dose 1; ZSP1601-Dose 2; ZSP1601-Dose 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects are required to meet the following criteria in order to be included in the trial:
• Signature signed informed consent before the trial, and fully understood the content, process and possible adverse reactions.
• Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.
• 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.
• Male and female subjects aged 18-65 (including 18 and 65).
• B ultrasound confirmed fatty liver.
• NASH diagnosis or NASH phenotypic diagnosis.
• Liver fat ≥10% at baseline (MRI-PDFF)

You may not qualify if:

• Excessive drinking for 3 consecutive months within 1 year before screening.
• Allergic constitution.
• Subjects who donated blood or bleeding profusely(\> 400 mL)in the 3 months preceding study screening.
• Subjects having a history of bariatric surgery or preparing for bariatric surgery recently.
• Subjects having a history of liver transplantation or plans for liver transplantation
• Any diseases that increase the risk of bleeding, such as hemorrhoids, acute gastritis or gastric and duodenal ulcers.
• Liver biopsy indicates cirrhosis or previous clinical diagnosis of cirrhosis.
• Type 1 diabetes mellitus.
• Uncontrolled type 2 diabetes mellitus (HbA1c≥8.0%)。
• 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.
• Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs.
• 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.
• Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
• Presence of clinically significant abnormalities in ECG or QTcB\>450ms in males,or QTcB\>470ms in females.
• HIV positive.

Sponsors & Collaborators

• Guangdong Raynovent Biotech Co., Ltd: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Related Publications (1)

• Hu Y, Li H, Zhang H, Chen X, Chen J, Xu Z, You H, Dong R, Peng Y, Li J, Li X, Wu D, Zhang L, Cao D, Jin H, Qiu D, Yang A, Lou J, Zhu X, Niu J, Ding Y. ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial. Nat Commun. 2023 Oct 12;14(1):6409. doi: 10.1038/s41467-023-42162-0.

  PMID: 37828034 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 25, 2019
• Study Start: June 23, 2020
• Primary Completion: August 3, 2021
• Study Completion: August 3, 2021
• Last Updated: October 11, 2021

Record last verified: 2021-10

Locations

CN (1)