Clinical trial NCT06569524: Efficacy and Safety of Recombinant Human FGF21-Fc Fusion Protein for Injection (TQA2225/AP025) in Adult Subjects With Non-alcoholic Steatohepatitis (NASH)
Official title: A Double-blind, Placebo Randomized，Phase II Study to Evaluate the Efficacy and Safety of TQA2225/AP025 in Adults With Nonalcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-alcoholic Steatohepatitis
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: To determine the effect of 25 or 50mg TQA2225 vs matching placebo on liver biopsy (NASH CRN score) at Week 48 compared with Baseline
timeFrame: After week 48 of TQA2225/AP025 treatment
Secondary outcomes:
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline to week 48
Other outcomes:
Locations:
city: Lu'an
country: China
facility: Lu'an Traditional Chinese Medicine Hospital
state: Anhui
city: Lu'an
country: China
facility: Lu'an People's Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing You 'an Hospital, Capital Medical University
state: Beijing
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: Xiamen Traditional Chinese Medicine Hospital
state: Fujian
city: Wuwei
country: China
facility: Wuwei Cancer Hospital of Gansu Province
state: Gansu
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou Worker's Hospital
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou Liutie Central Hospital
state: Guangxi
city: Yulin
country: China
facility: YuLin Red Cross Hospital
state: Guangxi
city: Qingyuan
country: China
facility: Qingyuan Hospital Affiliated to Guangzhou Medical University (Qingyuan People's Hospital)
state: Guangzhou
city: Baoding
country: China
facility: Baoding First Central Hospital
state: Hebei
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Fifth Hospital of Shijiazhuang
state: Hebei
city: Shijiazhuang
country: China
facility: Shijiazhuang Hospital of Traditional Chinese Medicine
state: Hebei
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Puyang
country: China
facility: Puyang Oilfield General Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Sixth People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Third People's Hospital
state: Henan
city: Wuhan
country: China
facility: Huazhong University of Science Tongji Hospital, Tongji Medical College
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Yueyang
country: China
facility: Yueyang Central Hospital
state: Hunan
city: Chifeng
country: China
facility: Chifeng Hospital
state: Inner Mongolia
city: Jiangyin
country: China
facility: Jiangyin People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi Fifth People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
state: Jiangsu
city: Ganzhou
country: China
facility: Ganzhou Fifth People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital Affiliated to China Medical University
state: Liaoning
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pudong New Area Gongli Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pudong Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shanxi
city: Leshan
country: China
facility: Leshan People's Hospital
state: Sichuan
city: Luzhou
country: China
facility: Southwest Medical University Affiliated Hospital
state: Sichuan
city: Meishan
country: China
facility: Meishan People's Hospital
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Zigong
country: China
facility: The First People's Hospital of Zigong City
state: Sichuan
city: Tianjin
country: China
facility: The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
state: Tianjin
city: Puer
country: China
facility: Puer People's Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Shulan (Hangzhou) Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Rui'an People's Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Medical Treatment Center Lihuili Hospital
state: Zhejiang
city: Yiwu
country: China
facility: Yiwu Central Hospital
state: Zhejiang
city: Zhoushan
country: China
facility: Zhoushan Hospital
state: Zhejiang
city: Zhoukou
country: China
facility: Zhoukou Central Hospital
state: Zhoukou
Study officials:
References: