Clinical trial NCT06125405: Study of the Telitacicept in Pediatric Patients With Frequently Relapsing or Steroid Dependent Nephrotic Syndrome
Official title: Study of the Telitacicept in Pediatric Patients With Frequently Relapsing or Steroid Dependent Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nephrotic Syndrome in Children
Telitacicept
Keywords: Telitacicept
Frequently Relapsing Nephrotic Syndrome
Steroid Dependent Nephrotic Syndrome
Lead sponsor: The Children's Hospital of Zhejiang University School of Medicine
Sponsor class: OTHER
First posted: 2023-11-09
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 1-year relapse-free survival rate
timeFrame: 1-year period after enrollment
Secondary outcomes:
measure: Relapse of nephrotic syndrome during 12 months after enrollment
timeFrame: 1-year period after enrollment
measure: Number of relapses during 12 months follow up
timeFrame: 1-year period after enrollment
measure: The first time to relapse
timeFrame: 1-year period after enrollment
measure: Cumulative prednisone dosage (milligrams per kilogram per year)
timeFrame: 1-year period after enrollment
measure: Change in hemoglobin of the patients
timeFrame: 1-year period after enrollment
measure: Change in blood albumin of the patients
timeFrame: 1-year period after enrollment
measure: Change in renal function of the patients
timeFrame: 1-year period after enrollment
measure: Change in mass index (BMI) during 12-month period after enrollment
timeFrame: 1-year period after enrollment
Other outcomes:
measure: Adverse event
timeFrame: 1-year period after enrollment
Locations:
city: Hangzhou
country: China
facility: Children's Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Children's Hospital, Zhejiang University School of Medicine
name: Jianhua Mao, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
citation: Dhillon S. Telitacicept: First Approval. Drugs. 2021 Sep;81(14):1671-1675. doi: 10.1007/s40265-021-01591-1.
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.
citation: 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.
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.
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.
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.