The purpose of the study is to assess the effect of zigakibart on IgA nephropathy (IgAN) disease progression.
This is an open-label multicenter study where participants are randomized into one of two groups, where the only difference between the groups is the on-treatment biopsy time point, end of the first year of treatment (Group A) or at the end of the second year of treatment (Group B). The total study duration for each participant may be up to 125 weeks, including the maximum screening period (8 weeks), the treatment period (104 weeks), and the safety follow up period (13 weeks).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
zigakibart 600 mg sc injections every second week for 104 weeks (2 years)
Change in mesangial IgA deposition
Change in mesangial IgA deposition as assessed by intensity of immunofluorescence staining
Time frame: Baseline to Week 53 or 105
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of AEs and SAEs , including changes in vital signs, injection site reactions, laboratory results and Immunoglobulin responses to vaccination qualifying and reported as AEs
Time frame: Day 1 to Week 118
Change in MEST-C score
Change in MEST-C, a histologic scoring system used to assess disease prognosis in patients with IgA nephropathy, which includes the components mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T), crescents (C). All five components are scored by categorical values as listed below, where a higher score indicates involvement or a relatively greater degree of involvement (i.e., more severe pathology). 1. Mesangial hypercellularity * M0 (present in ≤50% of glomeruli) * M1 (present in \>50% of glomeruli) 2. Endocapillary hypercellularity * E0 (Absent) * E1 (Present) 3. Segmental glomerulosclerosis (more than four mesangial cells) * S0 (Absent) * S1 (Present) 4. Tubular atrophy/interstitial fibrosis * T0 (0-25% of cortical area) * T1 (26-50% of cortical area) * T2 (\>50% of cortical area) 5. Cellular or fibrocellular crescents * C0 (No crescents) * C1 (\>25% of glomeruli) * C2 (≥25% of glomeruli)
Time frame: Baseline to Week 53 or 105
Change in CD68+ cells in glomeruli and tubulo-interstitial compartment
Change in CD68+ cells, which are markers of inflammation
Time frame: Baseline to Week 53 or 105
Change in complement component C3c
Change in C3c, which is a marker of complement (part of the immune system) activation
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Colorado Kidney Care Nephrology
Denver, Colorado, United States
RECRUITINGAmerican Clinical Trials
Acworth, Georgia, United States
RECRUITINGUniv Of Iowa Hospitals And Clinics
Iowa City, Iowa, United States
RECRUITINGInter Med Consultants
Edina, Minnesota, United States
RECRUITINGNovartis Investigative Site
Serra, Espírito Santo, Brazil
RECRUITINGNovartis Investigative Site
Recife, Pernambuco, Brazil
RECRUITINGNovartis Investigative Site
Natal, Rio Grande do Norte, Brazil
RECRUITINGNovartis Investigative Site
Botucatu, São Paulo, Brazil
RECRUITINGNovartis Investigative Site
Beijing, China
RECRUITINGNovartis Investigative Site
Shanghai, China
RECRUITING...and 19 more locations
Time frame: Baseline to Week 53 or 105
Change in UPCR
Change in the ratio of urine protein to urine creatinine (UPCR), based on 24-hour urine collection
Time frame: Baseline to Week 53 and 105
Change in eGFR
Change in estimated glomerular filtration rate (eGFR)
Time frame: Baseline to Week 53 and 105
Change in albuminuria
Change in urine albumin - creatinine ratio (UACR), based on 24-hour urine collection
Time frame: Baseline to Week 53 and 105
Change in hematuria
Change in presence of red blood cells in urine
Time frame: Baseline to Week 53 and 105
Change in serum IgA, IgM and IgG
Immunoglobulin (IgA, IgG and IgM) levels will be assessed from blood samples
Time frame: Baseline to Week 13, 29, 53, 79 and 105
Serum zigakibart concentrations
Serum concentration values will be provided
Time frame: Baseline, Week 13, 29, 66, 79 and 105
Circulating anti-zigakibart antibodies
Number of participants with circulating binding and neutralizing anti-drug antibodies (ADA/Nab) in blood will be provided
Time frame: Baseline, Week 13, 29, 66, 79 and 105