ZSP1601 / Guangdong Zhongsheng Pharma - LARVOL DELTA

A Randomized, Double-blind, Placebo-controlled Study of ZSP1601 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=180 | Active, not recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Recruiting ➔ Active, not recruiting | Phase classification: P2b ➔ P2

Enrollment closed • Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease. (PubMed, J Clin Transl Hepatol) - "Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs...Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications."

Journal • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Type 2 Diabetes Mellitus • FGF21 • TNFA

Dose Finding for ZSP1601 in Patients with Nonalcoholic Steatohepatitis Using Population pharmacokinetics and Exposure-Response Approach. (PubMed, Eur J Pharm Sci) - "The PopPK model and ER analysis, based on available data, comprehensively characterizes ZSP1601's pharmacokinetic, safety and efficacy profile, aiding informed decisions regarding dosage selection for the drug's complete developmental trajectory. The exposure-response (ER) analysis yields quantitative insights into the optimal balance of efficacy and safety within different dosage regimens for patient administration. In light of these findings, the dose regimen of 100 mg administered twice daily is proposed for subsequent clinical investigations."

Journal • PK/PD data • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pain

ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial. (PubMed, Nat Commun) - P1/2 | "Diarrhea, transiently elevated creatinine and adaptive headache were frequently reported adverse drug reaction. We conclude that ZSP1601 is well-tolerated and safe, showing effective improvement in liver chemistries, liver fat content and fibrosis in patients with NAFLD."

Clinical • Journal • P1/2 data • Fibrosis • Hepatology • Immunology • Non-alcoholic Fatty Liver Disease • Pain

A Randomized, Double-blind, Placebo-controlled Study of ZSP1601 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2b | N=180 | Recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2023 ➔ Jun 2023

Enrollment open • Trial initiation date • Hepatology • Non-alcoholic Steatohepatitis

A Randomized, Double-blind, Placebo-controlled Study of ZSP1601 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2b | N=180 | Not yet recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P2b trial • Hepatology • Non-alcoholic Steatohepatitis

Safety, pharmacokinetics and efficacy of the novel pan-phosphodiesterase inhibitor ZSP1601 in 36 NASH patients: a double-blinded, placebo-controlled, multiple-dose escalation phase Ib study (EASL-ILC 2022) - P1/2 | "The results of this clinical trial showed that a significant reduction in liver fat by MRI-PDFF and ALT level of NASH patients enrolled after 28-days treatment. The phase 1b study suggested that ZSP1601 is safe and effective. The efficacy of 50 mg BID and 100 mg BID cohortwere better than the 50 mg QD cohort and placebo cohort."

Clinical • P1 data • PK/PD data • Cardiovascular • Dyspepsia • Fibrosis • Hepatology • Hypertension • Immunology • Inflammation • Non-alcoholic Steatohepatitis • Pain • Portal Hypertension • KRT18 • TNFA

[VIRTUAL] SAFETY, PHARMACOKINETICS AND EFFICACY OF THE NOVEL PAN-PHOSPHODIESTERASE INHIBITOR ZSP1601 IN 36 NASH PATIENTS: A DOUBLE-BLINDED, PLACEBO-CONTROLLED, MULTIPLE-DOSE ESCALATION PHASE IB STUDY INTERIM ANALYSIS (AASLD 2021) - "It was observed that a significant reduction in liver fat by MRI-PDFF and ALT level of NASH patients after 28-days treatment . The phase 1b study suggested that ZSP1601 is safe and effective. Comparing with the results of the new drugs clinical study for NASH, the interim results of ZSP1601 are inspiring."

Clinical • P1 data • PK/PD data • Dyspepsia • Hepatology • Non-alcoholic Steatohepatitis • Pain • KRT18 • MRI • TNFA

Tolerability, Efficacy, and PK of ZSP1601 in Patients With Non-Alcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P1/2; N=37; Completed; Sponsor: Guangdong Raynovent Biotech Co., Ltd; Recruiting ➔ Completed

Clinical • Trial completion • Hepatology • Non-alcoholic Steatohepatitis • MRI • TNFA

Tolerability, Efficacy, and PK of ZSP1601 in Patients With Non-Alcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P1/2; N=36; Recruiting; Sponsor: Guangdong Raynovent Biotech Co., Ltd; Trial completion date: Jun 2021 ➔ Sep 2021; Trial primary completion date: Dec 2020 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • Hepatology • Non-alcoholic Steatohepatitis • MRI • TNFA

Safety, tolerability, and pharmacokinetics of the novel pan-phosphodiesterase inhibitor ZSP1601 in healthy subjects: a double-blinded, placebo-controlled first-in-human single-dose and multiple-dose escalation and food effect study. (PubMed, Expert Opin Investig Drugs) - P1 | "All adverse events (AEs) were assessed as mild or moderate, with headaches as the most common. The highest single doses (275 and 350 mg) yielded more AEs, yet the rates were similar with the placebo cohorts in the MAD study. The safety and PK profiles of ZSP1601 support further efficacy evaluation in nonalcoholic steatohepatitis patients.Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03392779)."

Clinical • Journal • P1 data • PK/PD data • Hepatology • Non-alcoholic Steatohepatitis • Pain

Tolerability, Efficacy, and PK of ZSP1601 in Patients With Non-Alcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P1/2; N=36; Recruiting; Sponsor: Guangdong Raynovent Biotech Co., Ltd; Not yet recruiting ➔ Recruiting; Trial completion date: Jul 2020 ➔ Jun 2021; Initiation date: Nov 2019 ➔ Jun 2020; Trial primary completion date: Jun 2020 ➔ Dec 2020

Clinical • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • MRI