Study of the Telitacicept in Pediatric Patients With Frequently Relapsing or Steroid Dependent Nephrotic Syndrome

Nephrotic Syndrome in Children Clinical Trial

— STERN  

Official title:

Study of the Telitacicept in Pediatric Patients With Frequently Relapsing or Steroid Dependent Nephrotic Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06125405
• Other study ID #: STERN
• Status: Recruiting
• Phase: Phase 3
• Start date: November 24, 2023
• Est. completion date: October 24, 2027

Study information

• Verified date: November 2023
• Source: The Children's Hospital of Zhejiang University School of Medicine
• Contact: Jianhua Mao, MD
• Phone: 86057186670015
• Email: maojh88[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective is to evaluate the effectiveness of telitacicept in pediatric patients with frequently relapsing or steroid dependent nephrotic syndrome within the 52-week follow-up.

Description:

Nephrotic syndrome(NS) is the most common glomerular disease in children. Approximately 45-50% of patients with nephrotic syndrome exhibit frequent relapses or are dependent on steroid therapy. Frequent relapses or steroid dependence in nephrotic syndrome have been challenging issues for clinicians. Long-term, repeated, and high-dose oral steroid use can lead to side effects such as obesity, delayed development, hypertension, diabetes, glaucoma, osteoporosis, and increased susceptibility to infections. The addition of traditional immunosuppressants such as cyclophosphamide and tacrolimus can cause severe and irreversible side effects. Therefore, exploring new drugs and their application protocols is particularly important. Telitacicept has a unique dual-target mechanism that can inhibit B cell maturation and differentiation at multiple stages, thereby inhibiting B cell activity. Clinical studies have confirmed its significant efficacy in various kidney diseases, such as lupus nephritis, IgA nephropathy, and adult recurrent minimal change nephrotic syndrome; moreover, it has good safety profiles.

Therefore, through this prospective, single-center, open-label clinical trial, we aim to evaluate whether telitacicept provides superior efficacy compared to existing conventional treatment regimens for childhood frequent relapse (FR) or steroid-dependent (SD) nephrotic syndrome (NS), and assess its safety profile. Our goal is to provide an optimized treatment plan for childhood FRNS or SDNS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 24, 2027
• Est. primary completion date: October 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

• Sensitive but frequent relapses or steroids dependence nephrotic syndrome

• Age: 2 to 18 years old

• Normal renal function: estimated glomerular filtration rate =90ml/ min/1.73m2

• Morning urine protein <1+ or urine protein-creatinine ratio <0.2g/g (<20 mg/ mmol) for 3 consecutive days and above when in enroll

• No rituximab was used within 6 months, no tacrolimus, mycophenolate mofetil, cyclosporine A, or cyclophosphamide was used within 3 months, no ACTH was used within 3 months prior to the enrollment

Exclusion Criteria:

• Family history of nephrotic syndrome, chronic glomerulonephritis or uremia

• Leukopenia (White Blood Cells = 3.0 * 10^9 / L)

• Moderate to severe anemia (hemoglobin <9.0 g/dL)

• Thrombocytopenia (platelet count <100*10^12/L)

• Positive Hepatitis B virus serological indicators (Hepatitis B surface antigen or / and Hepatitis B virus e antigen or / and Hepatitis B core antibody), Hepatitis C virus-positive or patients with abnormal liver function (2 or more times of alamine aminotransferase or total bilirubin was exceeded the normal value, and continued to rise for 2 weeks)

• There are chronic active infections such as Epstein-Barrvirus, cytomegalovirus or Mycobacterium tuberculosis, and the usage of steroids and immunosuppressive agents may aggravate the state of an illness

• Secondary nephrotic syndrome (such as purpuric nephritis, lupus nephritis, etc.)

• Those who with hematological or endocrine system diseases as well as serious organs illness such as heart, liver or kidney

• Those who with other autoimmune diseases or primary immunodeficiencies or tumors

• Those who have participated in other clinical trials within three months prior to the enrollment

• Those who was not suitable for participating this study judged by investigator

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Nephrotic Syndrome in Children
• Syndrome

Intervention

Drug:
• Telitacicept
The study duration was 52 weeks, with the experimental group receiving subcutaneous injections of Telitacicept once weekly for a total of 52 weeks.

Locations

Country	Name	City	State
China	Children's Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
The Children's Hospital of Zhejiang University School of Medicine

Country where clinical trial is conducted

China, 

References & Publications (10)

Cai J, Gao D, Liu D, Liu Z. Telitacicept for autoimmune nephropathy. Front Immunol. 2023 Jun 5;14:1169084. doi: 10.3389/fimmu.2023.1169084. eCollection 2023. — View Citation

Chen R, Fu R, Lin Z, Huang C, Huang W. The efficacy and safety of telitacicept for the treatment of systemic lupus erythematosus: a real life observational study. Lupus. 2023 Jan;32(1):94-100. doi: 10.1177/09612033221141253. Epub 2022 Nov 23. — View Citation

Dhillon S. Telitacicept: First Approval. Drugs. 2021 Sep;81(14):1671-1675. doi: 10.1007/s40265-021-01591-1. — View Citation

Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003 Aug 23;362(9384):629-39. doi: 10.1016/S0140-6736(03)14184-0. — View Citation

Filler G, Young E, Geier P, Carpenter B, Drukker A, Feber J. Is there really an increase in non-minimal change nephrotic syndrome in children? Am J Kidney Dis. 2003 Dec;42(6):1107-13. doi: 10.1053/j.ajkd.2003.08.010. — View Citation

Li S, Ding L, Yang YJ, Yang XD. Telitacicept for minimal change disease. Kaohsiung J Med Sci. 2023 Jul;39(7):748-749. doi: 10.1002/kjm2.12719. No abstract available. — View Citation

Lv J, Liu L, Hao C, Li G, Fu P, Xing G, Zheng H, Chen N, Wang C, Luo P, Xie D, Zuo L, Li R, Mao Y, Dong S, Zhang P, Zheng H, Wang Y, Qin W, Wang W, Li L, Jiao W, Fang J, Zhang H. Randomized Phase 2 Trial of Telitacicept in Patients With IgA Nephropathy With Persistent Proteinuria. Kidney Int Rep. 2022 Dec 29;8(3):499-506. doi: 10.1016/j.ekir.2022.12.014. eCollection 2023 Mar. — View Citation

Shi F, Xue R, Zhou X, Shen P, Wang S, Yang Y. Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease. Immunopharmacol Immunotoxicol. 2021 Dec;43(6):666-673. doi: 10.1080/08923973.2021.1973493. Epub 2021 Sep 14. — View Citation

Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol. 1997 May;8(5):769-76. doi: 10.1681/ASN.V85769. — View Citation

Veltkamp F, Rensma LR, Bouts AHM; LEARNS consortium. Incidence and Relapse of Idiopathic Nephrotic Syndrome: Meta-analysis. Pediatrics. 2021 Jul;148(1):e2020029249. doi: 10.1542/peds.2020-029249. Epub 2021 Jun 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse event	The number of harmful reactions and the types of adverse events during the study	1-year period after enrollment
Primary	1-year relapse-free survival rate	The rate of no relapse within 1 year	1-year period after enrollment
Secondary	Relapse of nephrotic syndrome during 12 months after enrollment	Proportion of patients with one or more relapse(s) of nephrotic syndrome	1-year period after enrollment
Secondary	Number of relapses during 12 months follow up	Number of nephrotic syndrome relapses per patient year during the 12 months period after enrollment	1-year period after enrollment
Secondary	The first time to relapse	The first time to relapse after patients taking part in this study	1-year period after enrollment
Secondary	Cumulative prednisone dosage (milligrams per kilogram per year)	The total dosage of prednisones from the beginning to the end of the trial	1-year period after enrollment
Secondary	Change in hemoglobin of the patients	The changes of hemoglobin (g/L) in each follow-up during the study	1-year period after enrollment
Secondary	Change in blood albumin of the patients	The changes of blood albumin (g/L)in each follow-up during the study	1-year period after enrollment
Secondary	Change in renal function of the patients	The change for renal function was judged by the changes of estimated glomerular filtration rate (eGFR in ml/min/1.73m^2) in each follow-up during the study	1-year period after enrollment
Secondary	Change in mass index (BMI) during 12-month period after enrollment	Changes in standard deviation scores for weight (Wt in kilograms), height (Ht in meters) will be combined to report body mass index (BMI in kg/m^2) during 12-month period after enrollment	1-year period after enrollment