A Study to Assess the Effects of Zigakibart on IgA Nephropathy. (SHIFT)

An Open-label, Multicenter Study to Assess the Effect of Zigakibart Treatment on Histologic, Circulating, and Excreted Markers of Kidney Disease and Dysfunction in Adult Patients With IgA Nephropathy.

The purpose of the study is to assess the effect of zigakibart on IgA nephropathy (IgAN) disease progression.

Study Overview

• Status: Recruiting
• Conditions: Immunoglobulin A Nephropathy (IgAN)
• Intervention / Treatment: Biological: zigakibart

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).

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com

Study Locations

• China
  • Shanghai, China, 200025
    • Recruiting
    • Novartis Investigative Site
• Japan
  • Miyazaki, Japan, 889-1692
    • Recruiting
    • Novartis Investigative Site
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 213-8587
      • Recruiting
      • Novartis Investigative Site
• Poland
  • Opole, Poland, 45-401
    • Recruiting
    • Novartis Investigative Site
• South Korea
  • Seoul
    • Seoul, Seoul, South Korea, 03080
      • Recruiting
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • Novartis Investigative Site
• United States
  • Colorado
    • Denver, Colorado, United States, 80230
      • Recruiting
      • Colorado Kidney Care Nephrology
      • Principal Investigator: Laura Kooienga
      • Contact: Leigh Collins; Email: lcollins@cokidneycare.com
  • Georgia
    • Acworth, Georgia, United States, 30101
      • Recruiting
      • American Clinical Trials
      • Principal Investigator: Chinedu Nweke
      • Contact: Chidi Asuzu; Email: chidi.asuzu@cowryhealth.com
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Recruiting
      • Inter Med Consultants
      • Principal Investigator: Jonathan Tolins
      • Contact: Andrew Tran; Email: andrew.tran@davita.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Secondary forms of IgAN, as determined by the Investigator, diagnosis of IgA vasculitis, or any other nephropathy or chronic urinary tract disorder
• 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
• An average systolic blood pressure >150 mmHg or average diastolic blood pressure >90 mmHg based on three measurements at Screening
• Treatment with complement pathway inhibitors, mycophenolic acids, systemic calcineurin inhibitors or corticosteroids, immunosuppressive or immunomodulatory agents within 12 months prior to screening
• Acute kidney injury (AKI), defined by AKI network criteria, within 4 weeks prior to screening
• Current treatment with anti-APRIL monoclonal antibodies or dual APRIL/BAFF inhibitors or past treatment of the same at any time for >3 consecutive months prior to screening
• Planned initiation of, or recently (within 24 weeks) initiated, treatment with glucagon-like peptide-1 agonists at screening

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: zigakibart; zigakibart injections every second week for two years	Biological: zigakibart; zigakibart 600 mg sc injections every second week for 104 weeks (2 years)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mesangial IgA deposition	Change in mesangial IgA deposition as assessed by intensity of immunofluorescence staining	Baseline to Week 53 or 105

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 1 to Week 118
Change in CD68+ cells in glomeruli and tubulo-interstitial compartment	Change in CD68+ cells, which are markers of inflammation	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	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	Baseline to Week 53 and 105
Change in eGFR	Change in estimated glomerular filtration rate (eGFR)	Baseline to Week 53 and 105
Change in albuminuria	Change in urine albumin - creatinine ratio (UACR), based on 24-hour urine collection	Baseline to Week 53 and 105
Change in hematuria	Change in presence of red blood cells in urine	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	Baseline to Week 13, 29, 53, 79 and 105
Serum zigakibart concentrations	Serum concentration values will be provided	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	Baseline, Week 13, 29, 66, 79 and 105
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).; Mesangial hypercellularityM0 (present in ≤50% of glomeruli)M1 (present in >50% of glomeruli); Endocapillary hypercellularityE0 (Absent)E1 (Present); Segmental glomerulosclerosis (more than four mesangial cells)S0 (Absent)S1 (Present); Tubular atrophy/interstitial fibrosisT0 (0-25% of cortical area)T1 (26-50% of cortical area)T2 (>50% of cortical area); Cellular or fibrocellular crescentsC0 (No crescents)C1 (>25% of glomeruli)C2 (≥25% of glomeruli)	Baseline to Week 53 or 105

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2026
• Primary Completion (Estimated): July 12, 2030
• Study Completion (Estimated): October 18, 2030

Study Registration Dates

• First Submitted: August 21, 2025
• First Submitted That Met QC Criteria: August 21, 2025
• First Posted (Actual): August 28, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: proteinuria; kidney; adults; IgA nephropathy; biopsy; IgAN; FUB523; zigakibart; anit-APRIL; SHIFT
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Urination Disorders; Urological Manifestations; Glomerulonephritis; Nephritis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Glomerulonephritis, IGA; Proteinuria
• Other Study ID Numbers: CFUB523A12201; 2024-519699-24 (Other Identifier: EMA (EU CT Number)); U1111-1323-5075 (Other Identifier: WHO UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No