Nephrotic Syndrome in Children
Conditions
Brief summary
This is an open - label study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of SG301 Subcutaneous injection in children with frequently relapsing or steroid - dependent nephrotic syndrome.
Detailed description
This study will recruit children aged 6 - 18 with frequently relapsing or steroid - dependent nephrotic syndrome, who have morning urine protein \< 1 + or urine protein / creatinine \< 0.2 g/g (\<20 mg/mmol) for at least three consecutive days after steroid treatment. The study will stratify participants into two age groups:≥6 - \<12 years and≥12 - \<18 years. Recruitment will start with the 12 - 18 - year - old group. After collecting sufficient safety and clinical pharmacology data to support moving to lower age groups, the 6 - 12 - year - old group will be recruited. For every 1 to 3 participants enrolled, there will be a phased data review to guide further recruitment. The trial has three phases: screening (D - 28\ D - 1), treatment (12 - week), and follow - up (40 - week). The enrolled participants will be treated with 10 mg/kg SG301 Subcutaneous injection subcutaneously. They will receive weekly injections for the first six weeks, then every two weeks for three times, totaling nine injections.
Interventions
DRUGSG301 Subcutaneous injection
Subcutaneous injection every weeks (QW\*6),subsequently, administer it once every two weeks for a total of three times (Q2W\*3). The total number of doses is nine.
Sponsors
Mao Jianhua
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 6 - 18 years. 2. Steroid-sensitive nephrotic syndrome with frequent relapses (FRNS) or steroid dependence (SDNS). 3. Normal renal function: eGFR≥90 ml/min/1.73m². 4. After steroid treatment, morning urine protein\<1 + or urine protein/creatinine\<0.2 g/g (\<20 mg/mmol) for ≥3 consecutive days. 5. Within 7 days before enrollment, blood tests (without growth factors or transfusions) must meet: hemoglobin\>80 g/L; platelets\>75×10⁹/L; neutrophils\>1.5×10⁹/L. 6. Prothrombin time/INR≤1.5×ULN, unless due to anticoagulation. 7. No Tacrolimus, cyclosporine A, mycophenolate mofetil, belimumab, levamisole, azathioprine, or cyclophosphamide in prior 2 months; no rituximab or obinutuzumab in prior 6 months.
Exclusion criteria
1. Family history of nephrotic syndrome, chronic glomerulonephritis, or uremia. 2. Alanine aminotransferase \>2×ULN or total bilirubin\>2×ULN with a sustained increase for 2 weeks. 3. HBsAg or HBcAb positive with Hepatitis B virus DNA above the lower limit of normal; Hepatitis C virus antibody - positive with Hepatitis C virus RNA positive; HIV antibody - positive. 4. Chronic active infections (e.g., Epstein-Barr Virus, Cytomegalovirus, tuberculosis) that may worsen with steroids/ immunosuppressants. 5. Acute active infection (excluding onychomycosis) requiring systemic antibiotics/antivirals. 6. Secondary nephrotic syndrome (e.g.,immunoglobulin A - associated, lupus nephritis); steroid - resistant nephrotic syndrome (SRNS). 7. Other autoimmune diseases, primary immunodeficiency, or malignancy. 8. Prior anti - cluster of differentiation 38 (CD38) treatment. 9. Live/attenuated vaccine receipt or major surgery (non - diagnostic) within 4 weeks before first dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and rate of treatment-Emergent Adverse Events | From baseline through study completion, an average of 1 year | Number and percentage of adverse events which are calculated by worst CTCAE grade by CTCAE 5.0 |
| Relapse free survival rate | Average 1 year per subject | Relapse free survival rate at 6 and 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse frequency in times | From baseline through study completion, an average of 1 year | Proportion of relapsed participants |
| Time to Relapse | From baseline through study completion, an average of 1 year | Time to first relapse after enrollment |
| Serum creatinine | From baseline through study completion, an average of 1 year | Serum creatinine(SCr), SCr in mg/dl |
| estimated glomerular filtration rate | From baseline through study completion, an average of 1 year | Estimated glomerular filtration rate (eGFR), eGFR in ml/min/1.73m² |
| Cumulative corticosteroid dose | From baseline through study completion, an average of 1 year | The total amount of corticosteroids used during the study period, and the total amount of corticosteroids used in the 6 months prior to enrollment |
| SG301 anti-drug antibodies | From baseline through study completion, an average of 1 year | Number of subjects positive for anti-SG301 anti-drug antibodies |
| Neutralizing antibodies against SG301 | From baseline through study completion, an average of 1 year | the neutralizing antibody titer of anti-SG301 anti-drug antibodies |
| pharmacokinetics : Ctrough | From baseline through study completion, an average of 1 year | The trough concentration of SG301 |
Countries
China
Contacts
CONTACTYanyan Jin, Doctor
Outcome results
None listed