Immunoglobulin A Nephropathy (IgAN)Phase 2SHIFTNCT07146906
A Study to Assess the Effects of Zigakibart on IgA Nephropathy.
A Phase 2 study testing zigakibart in people with Immunoglobulin A Nephropathy (IgAN), run by Novartis Pharmaceuticals at 30 sites in 11 countries.
Trial summary
The purpose of the study is to assess the effect of zigakibart on IgA nephropathy (IgAN) disease progression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immunoglobulin A Nephropathy (IgAN)
- What is being tested?
- zigakibart
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 30 sitesin 11 countries
- Study dates
- 26 Mar 2026to 18 Oct 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
30 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
30 sites in 11 countries
United States5 sites, 5 recruiting
- Recruiting
American Clinical Trials
Acworth, Georgia, 30101
Chidi Asuzu, chidi.asuzu@cowryhealth.com
Chinedu Nweke
- Recruiting
Colorado Kidney Care Nephrology
Denver, Colorado, 80230
Georgi Krastev, gkrastev@cokidneycare.com
Laura Kooienga
- Recruiting
Inter Med Consultants
Edina, Minnesota, 55435
Charlene Newton, charlene.newton@davita.com
Jonathan Tolins
- Recruiting
Univ Of Iowa Hospitals And Clinics
Iowa City, Iowa, 52242
Christine Zabawa, +1 319 356 1826, christine-zabawa-hamilton@uiowa.edu
Lama Noureddine
- Recruiting
UC San Francisco Medical Center
San Francisco, California, 94143-0348
Juan Espinoza, +1 415 476 8338, juan.espinoza@ucsf.edu
Christopher Carlos
Brazil4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Botucatu, São Paulo, 3880-1001
- Recruiting
Novartis Investigative Site
Natal, Rio Grande do Norte, 59012-300
- Recruiting
Novartis Investigative Site
Recife, Pernambuco, 50740-900
- Recruiting
Novartis Investigative Site
Serra, Espírito Santo, 29160-750
Spain4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Barcelona, 08036
- Recruiting
Novartis Investigative Site
Pamplona, Navarre, 31008
- Recruiting
Novartis Investigative Site
Seville, 41013
- Recruiting
Novartis Investigative Site
Valencia, Valencia, 46017
Germany3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Hanover, 30625
- Recruiting
Novartis Investigative Site
Mainz, 55131
- Recruiting
Novartis Investigative Site
Munich, Bavaria, 81377
Italy3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Brescia, BS, 25123
- Recruiting
Novartis Investigative Site
Pavia, PV, 27100
- Recruiting
Novartis Investigative Site
Ranica, BG, 24020
China2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Beijing, 100034
- Recruiting
Novartis Investigative Site
Shanghai, 200025
Japan2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Kawasaki, Kanagawa, 2138587
- Recruiting
Novartis Investigative Site
Miyazaki, 8891692
Poland2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Lodz, 92-213
- Recruiting
Novartis Investigative Site
Opole, 45-401
South Korea2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Seoul, Seoul, 03080
- Recruiting
Novartis Investigative Site
Seoul, 03722
Taiwan2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Kaohsiung City, 833
- Recruiting
Novartis Investigative Site
Taipei, 10002
Czechia1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Prague, 128 08
About this study
Official title: 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.
Read the 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).
- Conditions
- Immunoglobulin A Nephropathy (IgAN)
- Being tested
- zigakibart
- Keywords
- zigakibart, FUB523, anit-APRIL, SHIFT, IgA nephropathy, IgAN, proteinuria, kidney, biopsy, adults
- Medical subject headings
- Glomerulonephritis, IGA, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zigakibartBiological
zigakibart 600 mg sc injections every second week for 104 weeks (2 years)
| Study group | Role | What they receive |
|---|---|---|
| zigakibart | Experimental | zigakibart injections every second week for two years Receives: Biological: zigakibart |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mesangial IgA deposition
Change in mesangial IgA deposition as assessed by intensity of immunofluorescence staining
Measured: Baseline to Week 53 or 105
Secondary outcomes (11)
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
Measured: 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).
- Mesangial hypercellularity
- M0 (present in ≤50% of glomeruli)
- M1 (present in >50% of glomeruli)
- Endocapillary hypercellularity
- E0 (Absent)
- E1 (Present)
- Segmental glomerulosclerosis (more than four mesangial cells)
- S0 (Absent)
- S1 (Present)
- Tubular atrophy/interstitial fibrosis
- T0 (0-25% of cortical area)
- T1 (26-50% of cortical area)
- T2 (>50% of cortical area)
- Cellular or fibrocellular crescents
- C0 (No crescents)
- C1 (>25% of glomeruli)
- C2 (≥25% of glomeruli)
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to Week 53 and 105
Change in eGFR
Change in estimated glomerular filtration rate (eGFR)
Measured: Baseline to Week 53 and 105
Change in albuminuria
Change in urine albumin - creatinine ratio (UACR), based on 24-hour urine collection
Measured: Baseline to Week 53 and 105
Change in hematuria
Change in presence of red blood cells in urine
Measured: 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
Measured: Baseline to Week 13, 29, 53, 79 and 105
Serum zigakibart concentrations
Serum concentration values will be provided
Measured: 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
Measured: Baseline, Week 13, 29, 66, 79 and 105
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2025
- Study start26 Mar 2026
- Primary completion12 Jul 2030 (estimated)
- Study completion18 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immunoglobulin A Nephropathy (IgAN)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Participants will be randomly assigned in a ratio of 1:1 to undergo the on-treatment biopsy at one of two possible timepoints
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07146906
- Sponsor's protocol ID
- CFUB523A12201
- Other IDs
- 2024-519699-24, U1111-1323-5075
- Acronym
- SHIFT
- Status last verified
- Oct 2026
- First submitted
- 21 Aug 2025
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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