A Study to Assess the Effects of Zigakibart on IgA Nephropathy.
- Conditions
- Immunoglobulin A Nephropathy (IgAN)
- Interventions
- Registration Number
- NCT07146906
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of the study is to assess the effect of zigakibart on IgA nephropathy (IgAN) disease progression.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 32
-
Primary IgAN, confirmed by kidney biopsy, within 5 years prior to Screening
-
eGFR ≥45 mL/min/1.73 m2, based on the 2021 CKD-EPI equation, at Screening
-
Persistent proteinuria, defined as either
- Total Urine Protein ≥0.5 g/day or UPCR ≥0.5 g/g in a 24-hour urine collection, at Screening, despite maximally tolerated dose or poorly tolerated supportive therapy or
- IgAN diagnosis <6 months prior to Screening with Total Urine Protein >1.5 g/day or UPCR >1.5 g/g in a 24-hour urine collection, at the time of clinical presentation or diagnosis
-
Body weight ≥45 kg and body mass index (BMI) ≤35.0 kg/m2, at Screening
- Secondary forms of IgAN, as determined by the Investigator, in the setting of systemic disorders, infections, autoimmune disorders or neoplasias
- Diagnosis of IgA vasculitis
- Total IgG <6.0 g/L at Screening
- Any chronic urinary tract disorder, including but not limited to retention, incontinence, and/or recurrent urinary tract infections
- Untreated hypertension or uncontrolled hypertension despite treatment (i.e., resistant hypertension)
- Treatment with immunosuppressive or other immunomodulatory agents within 52 weeks prior to Screening
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description zigakibart zigakibart zigakibart injections every second week for two years
- Primary Outcome Measures
Name Time Method Change in mesangial IgA deposition Baseline to Week 53 or 105 Change in mesangial IgA deposition as assessed by intensity of immunofluorescence staining
- Secondary Outcome Measures
Name Time Method Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 to Week 118 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
Change in MEST-C score Baseline to Week 53 or 105 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)
Change in CD68+ cells in glomeruli and tubulo-interstitial compartment Baseline to Week 53 or 105 Change in CD68+ cells, which are markers of inflammation
Change in complement component C3c Baseline to Week 53 or 105 Change in C3c, which is a marker of complement (part of the immune system) activation
Change in UPCR Baseline to Week 53 and 105 Change in the ratio of urine protein to urine creatinine (UPCR), based on 24-hour urine collection
Change in eGFR Baseline to Week 53 and 105 Change in estimated glomerular filtration rate (eGFR)
Change in albuminuria Baseline to Week 53 and 105 Change in urine albumin - creatinine ratio (UACR), based on 24-hour urine collection
Change in hematuria Baseline to Week 53 and 105 Change in presence of red blood cells in urine
Change in serum IgA, IgM and IgG Baseline to Week 13, 29, 53, 79 and 105 Immunoglobulin (IgA, IgG and IgM) levels will be assessed from blood samples
Serum zigakibart concentrations Baseline, Week 13, 29, 66, 79 and 105 Serum concentration values will be provided
Circulating anti-zigakibart antibodies Baseline, Week 13, 29, 66, 79 and 105 Number of participants with circulating binding and neutralizing anti-drug antibodies (ADA/Nab) in blood will be provided