Efficacy and Safety of Recombinant Human FGF21-Fc Fusion Protein for Injection (TQA2225/AP025) in Adult Subjects With Non-alcoholic Steatohepatitis (NASH)
- Conditions
- Non-alcoholic Steatohepatitis
- Interventions
- Drug: TQA2225/AP025 or TQA2225/AP025 Placebo 25mgDrug: TQA2225/AP025 or TQA2225/AP025 Placebo 50mg
- Registration Number
- NCT06569524
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
-
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:
- 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
- Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TQA2225/AP025 or TQA2225/AP025 Placebo 25mg TQA2225/AP025 or TQA2225/AP025 Placebo 25mg TQA2225/AP025 or TQA2225/AP025 Placebo administered 25mg by subcutaneous (SC) injection weekly for 48 weeks TQA2225/AP025 or TQA2225/AP025 Placebo 50mg TQA2225/AP025 or TQA2225/AP025 Placebo 50mg TQA2225/AP025 or TQA2225/AP025 Placebo administered 50mg by subcutaneous (SC) injection weekly for 48 weeks
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline to week 48 Number and percentage of adverse events and serious adverse events
Trial Locations
- Locations (53)
Mengchao Hepatobiliary Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Lu'an People's Hospital
🇨🇳Lu'an, Anhui, China
YuLin Red Cross Hospital
🇨🇳Yulin, Guangxi, China
Cangzhou Central Hospital
🇨🇳Cangzhou, Hebei, China
Lu'an Traditional Chinese Medicine Hospital
🇨🇳Lu'an, Anhui, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
Liuzhou Liutie Central Hospital
🇨🇳Liuzhou, Guangxi, China
Wuwei Cancer Hospital of Gansu Province
🇨🇳Wuwei, Gansu, China
Leshan People's Hospital
🇨🇳Leshan, Sichuan, China
Southwest Medical University Affiliated Hospital
🇨🇳Luzhou, Sichuan, China
Meishan People's Hospital
🇨🇳Meishan, Sichuan, China
The Sixth People's Hospital of Shenyang
🇨🇳Shenyang, Liaoning, China
Zhengzhou Third People's Hospital
🇨🇳Zhengzhou, Henan, China
The Second Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Mianyang Central Hospital
🇨🇳Mianyang, Sichuan, China
The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
🇨🇳Tianjin, Tianjin, China
Qingyuan Hospital Affiliated to Guangzhou Medical University (Qingyuan People's Hospital)
🇨🇳Qingyuan, Guangzhou, China
Puyang Oilfield General Hospital
🇨🇳Puyang, Henan, China
Zhengzhou Sixth People's Hospital
🇨🇳Zhengzhou, Henan, China
Jiangyin People's Hospital
🇨🇳Jiangyin, Jiangsu, China
Liaocheng People's Hospital
🇨🇳Liaocheng, Shandong, China
Shanghai Tongren Hospital
🇨🇳Shanghai, Shanghai, China
Fifth Hospital of Shijiazhuang
🇨🇳Shijiazhuang, Hebei, China
Luoyang Central Hospital
🇨🇳Luoyang, Henan, China
Shengjing Hospital Affiliated to China Medical University
🇨🇳Shenyang, Liaoning, China
Chifeng Hospital
🇨🇳Chifeng, Inner Mongolia, China
Shijiazhuang Hospital of Traditional Chinese Medicine
🇨🇳Shijiazhuang, Hebei, China
The First Affiliated Hospital of Xi 'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
The First People's Hospital of Zigong City
🇨🇳Zigong, Sichuan, China
Puer People's Hospital
🇨🇳Puer, Yunnan, China
Ningbo Medical Treatment Center Lihuili Hospital
🇨🇳Ningbo, Zhejiang, China
Zhoushan Hospital
🇨🇳Zhoushan, Zhejiang, China
Zhoukou Central Hospital
🇨🇳Zhoukou, Zhoukou, China
Shulan (Hangzhou) Hospital
🇨🇳Hangzhou, Zhejiang, China
Rui'an People's Hospital
🇨🇳Hangzhou, Zhejiang, China
Yueyang Central Hospital
🇨🇳Yueyang, Hunan, China
Beijing You 'an Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Xiamen Traditional Chinese Medicine Hospital
🇨🇳Xiamen, Fujian, China
Liuzhou Worker's Hospital
🇨🇳Liuzhou, Guangxi, China
Baoding First Central Hospital
🇨🇳Baoding, Hebei, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Wuxi Fifth People's Hospital
🇨🇳Wuxi, Jiangsu, China
Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
Affiliated Hospital of Jiangsu University
🇨🇳Zhenjiang, Jiangsu, China
Ganzhou Fifth People's Hospital
🇨🇳Ganzhou, Jiangxi, China
Shanghai Pudong Hospital
🇨🇳Shanghai, Shanghai, China
Shanxi Bethune Hospital
🇨🇳Taiyuan, Shanxi, China
Yiwu Central Hospital
🇨🇳Yiwu, Zhejiang, China
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shanghai Pudong New Area Gongli Hospital
🇨🇳Shanghai, Shanghai, China
Huazhong University of Science Tongji Hospital, Tongji Medical College
🇨🇳Wuhan, Hubei, China