Non-alcoholic Steatohepatitis
Conditions
Brief summary
A randomized, double-blind, placebo-controlled Phase II study，to evaluate the efficacy and safety of TQA2225/AP025 in Patients With Non-Alcoholic Steatohepatitis (NASH)
Interventions
DRUGTQA2225/AP025 or TQA2225/AP025 Placebo 25mg
To evaluate the efficacy and safety of TQA2225/AP025 (25mg) in patients with Non-Alcoholic Steatohepatitis (NASH)
DRUGTQA2225/AP025 or TQA2225/AP025 Placebo 50mg
To evaluate the efficacy and safety of TQA2225/AP025 (50mg) in patients with Non-Alcoholic Steatohepatitis (NASH)
Sponsors
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Must be willing to participate in the study and provide written informed consent. * Male or female aged 18 ≤ age \< 75 at the time of signing the informed consent. * Must have had prior liver biopsy within 180 days of randomization with fibrosis stage 1 to 3 and a NAS of ≥4 with at least a score of 1 in each of the lobular inflammation and ballooning degeneration. * Confirmation of ≥10% liver fat content on Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). * Weight changes≤5% in the 6 weeks prior to randomization. * No qualitative change in dose for the drugs listed below: 1. Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months 2. Vitamin E (if at a dose ≥400 IU/day): for at least 6 months 3. Statins: for at least 3 months * Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 6 month after treatment discontinuation.
Exclusion criteria
* Documented causes of chronic liver disease other than NASH * Type 1 diabetes or uncontrolled Type 2 diabetes defined as:Hemoglobin A1c ≥9% at screening，Fasting blood glucose≥13.9mmol/l * Uncontrolled hypertension at Screening (values ≥160/100 mm Hg) * History or presence of cirrhosis * Subjects with any type of active malignancy or a history of malignancy (except cervical cancer or non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma and papillary thyroid carcinoma) that has been cured for more than 5 years prior to the screening period; * Unable or unwilling to undergo liver biopsy according to research requirements. * History of weight loss surgery within 5 years (inclusive) prior to screening * A major surgery was performed 3 months prior to signing the Informed Consent Form (ICF), or planned during the study period. * Have experienced any bone trauma, fracture, or bone surgery within ≤ 2 months prior to screening. * When screening, according to the results of dual energy X-ray absorptiometry (DXA) examination, it meets the criteria for osteoporosis: T≤ -2.5 * Recent history of drug abuse (defined as ≤ 2 years). * Patient participating in other clinical trials of drugs or medical devices within 3 months prior to screening. * Abnormal laboratory test values：ALT or AST \>5 × ULN；Serum ALP≥2× ULN；eGFR\<60mL/min；INR\>1.3× ULN；platelets \< LLN. * Pregnant or breastfeeding women. * Liver transplantation history or planned liver transplantation * Contraindications for MRI examination * Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the effect of 25 or 50mg TQA2225 vs matching placebo on liver biopsy (NASH CRN score) at Week 48 compared with Baseline | After week 48 of TQA2225/AP025 treatment | 1. Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage OR 2. Proportion with at least a 1-point improvement in fibrosis stage with no worsening of NAS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline to week 48 | Number and percentage of adverse events and serious adverse events |
Countries
China
Contacts
Primary ContactJunqi Niu, Doctor
Backup ContactZujiang Yu, Doctor
Outcome results
None listed