Clinical trial NCT05799287: A Study of Telitacicept in Patients with Primary Immunoglobulin A（IgA） Nephropathy
Official title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Telitacicept in Patients with Primary IgA Nephropathy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Primary IgA Nephropathy
Keywords: Autoimmune Diseases
Immune System Diseases
IgA Nephropathy
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-04-05
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of Telitacicept in patients with primary IgA nephropathy at risk of progressing to end-stage renal disease(ESRD), despite maximum tolerated treatment with renin-angiotensin system(RAS) blockade using angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type I receptor blockers (ARBs).

Detailed description: This study consists of a 5-week screening period, a double-blind treatment period divided into phase A and phase B. Eligible subjects will be randomly assigned in a 1:1 ratio to receive either Telitacicept 240mg or placebo. Subjects will be given subcutaneous injection（SC） Telitacicept or placebo once a week for a total of 39 doses in phase A and once every 2 weeks for a total of 32 doses in phase B.

Primary endpoint of phase A will be measured at week 39. Primary endpoint of phase B will be measured at week 104.

Eligibility criteria: Inclusion Criteria:

1. Voluntary informed consent provided;
2. Male or female aged ≥ 18 years old;
3. IgA nephropathy confirmed by pathological biopsy;
4. During the screening period, UPCR ≥ 0.8 g/g or 24-hour urine protein ≥ 1.0 g/day based on 24-hour urine collection at Visit 1 and/or Visit 2 and at Visit 3;
5. eGFR ≥ 30 mL/min per 1.73 m\^2 (using the CKD-EPI);
6. Have been on a treatment regimen including ACEI/ARB for 12 weeks and on a stable use of ACEI/ARB medication at the maximum tolerated dose/maximum allowable dose within 4 weeks prior to randomization. Subjects who use both ACEIs and ARBs will be excluded.

Exclusion Criteria:

1. Clinically significant abnormal laboratory tests;
2. Secondary IgA nephropathy;
3. Other types of glomerular disease such as crescentic glomerulonephritis（\>50%）, minimal change nephropathy with IgA deposition;
4. Renal transplant;
5. Cirrhosis, as assessed by the investigator;
6. Experienced any of the following cardiovascular and cerebrovascular events within 24 weeks prior to randomization: myocardial infarction, unstable angina, ventricular arrhythmia, New York Heart Association（NYHA） Class II or higher heart failure, stroke, etc.;
7. Sitting position SBP\>140 mmHg or DBP\>90 mmHg for at least once at 2 visits during the screening period;
8. Poorly controlled type 1 and type 2 diabetes (glycated hemoglobin A1c\[HbA1c\]\>8% or 64mmol/mol);
9. Received immunosuppressants within 12 weeks prior to randomization, including but not limited to cyclophosphamide, azathioprine, mycophenolate, leflunomide, tacrolimus, cyclosporine, Tripterygium wilfordii;
10. Received anti-CD20 therapy (for example, Rituximab Injection) within 24 weeks prior to randomization;
11. Received systemic glucocorticoid treatment within 12 weeks prior to randomization, excluding the followings: ① received systemic treatment with prednisolone ≤ 0.5mg/kg or equivalent glucocorticoid for non- IgA nephropathy for no more than 3 courses (≤ 2 weeks per course) in the past 52 weeks; ② topical administration or nasal inhalation;
12. Hospitalization or intravenous anti-infective therapy for active infection within 4 weeks prior to randomization;
13. Active tuberculosis and untreated latent tuberculosis;
14. Hepatitis B: patients with active hepatitis (patients with positive HBsAg) or latent hepatitis B (patients with positive HBcAb and positive HBV-DNA);
15. Hepatitis C;
16. Patients with HIV;
17. Malignancy within the past 5 years, except for treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, colon polyps, or cervical cancer in situ;
18. Pregnant women, lactating women, and subjects with childbearing plans during the trial;
19. Allergic to biological products of human origin;
20. Received any investigational therapy within 4 weeks or within 5 times the half-life of the investigational product (whichever is longer) prior to randomization;
21. Received live vaccination within 4 weeks prior to randomization;
22. Drug or alcohol abuse/dependence within 52 weeks prior to randomization;
23. Not suitable for the study in the opinion of the investigator.

Primary outcomes:
measure: Change from baseline in urine protein creatinine ratio (UPCR)
timeFrame: 39 weeks
measure: Annualized estimated glomerular filtration rate (eGFR) slope
timeFrame: 104 weeks
Secondary outcomes:
measure: Proportion of patients with a 30% decrease in estimated glomerular filtration rate (eGFR) compared with baseline
timeFrame: 39 weeks
measure: Time to 30% reduction from baseline in eGFR
timeFrame: up to 104 weeks
measure: Proportion of patients with a 40% decrease in estimated glomerular filtration rate (eGFR) compared with baseline
timeFrame: up to 104 weeks
measure: Proportion of patients received rescue treatment.
timeFrame: up to 104 weeks
measure: Incidence and severity of adverse events
timeFrame: up to 104 weeks
measure: Change from baseline in urine protein creatinine ratio (UPCR)
timeFrame: 52 weeks,78 weeks,104 weeks
measure: Change from baseline in estimated glomerular filtration rate (eGFR)
timeFrame: 39 weeks, 52 weeks,78 weeks,104 weeks
measure: Change from baseline in UACR in urine albumin-to-creatinine ratio (UACR)
timeFrame: 39 weeks, 52 weeks,78 weeks,104 weeks
measure: Time to composite endpoint event
timeFrame: up to 104 weeks
measure: Proportion of patients achieving urine protein creatinine ratio (UPCR) < 0.8 g/g
timeFrame: 39 weeks, 52 weeks,78 weeks,104 weeks
measure: Annualized estimated glomerular filtration rate (eGFR) slope
timeFrame: 52 weeks
Other outcomes:
measure: Change from baseline in 24-hour urine protein
timeFrame: 39 weeks
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Wuhu
country: China
facility: Yijishan Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Anzhen Hospital Affiliated to Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tsinghua Changgeng Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Shougang Hospital
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Army Medical University
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital Affiliated to Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Hospital
state: Gansu
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Shantou
country: China
facility: Shantou Central Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Longgang District People's Hospital of Shenzhen
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Zhuhai
country: China
facility: Zhuhai People's Hospital
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical College
state: Guangxi Zhuang Autonomous Region
city: Liuzhou
country: China
facility: Liuzhou Workers Hospital
state: Guangxi Zhuang Autonomous Region
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi Zhuang Autonomous Region
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Handan
country: China
facility: Handan First Hospital
state: Hebei
city: Qinhuangdao
country: China
facility: First Hospital of Qinhuangdao
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Zhangjiakou
country: China
facility: The First Affiliated Hospital of Hebei North University
state: Hebei
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
state: Inner Mongolia Autonomous Region
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia Autonomous Region
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Province People's Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: General Hospital of Northern Theatre Command of Chinese People's Liberation Army
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The Affiliated Central Hospital of Shenyang Medical College
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia Hui Autonomous Region
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Qianfoshan Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Yibin
country: China
facility: The Second People's Hospital of Yibin
state: Sichuan
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Urumqi
country: China
facility: People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang Uygur Autonomous Region
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang Uygur Autonomous Region
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Jinhua
country: China
facility: Jinhua Municipal Central Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo No.2 Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Traditional Chinese Medicine Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Tongde Hospital of Zhejing Province
state: Zhejing
Study officials:
affiliation: Peking University First Hospital
name: Jicheng Lv, M.D.
role: PRINCIPAL_INVESTIGATOR
References: