Zigakibart treatment for IgA nephropathy

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.

This trial will test whether the drug zigakibart can slow disease progression in people with biopsy-confirmed IgA nephropathy and persistent proteinuria.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Novartis (industry)
• Locations: 8 sites (Denver, Colorado and 7 other locations)
• Trial ID: NCT07146906 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter, randomized Phase 2 study of zigakibart in participants with primary IgA nephropathy. Participants are assigned to one of two groups that differ only by when an on-treatment kidney biopsy is done: at the end of year one (Group A) or at the end of year two (Group B). The treatment period lasts 104 weeks, with a screening window and a 13-week safety follow-up for a total possible participation time of up to 125 weeks. Enrollment requires biopsy-confirmed primary IgAN, eGFR ≥45 mL/min/1.73 m2, and persistent proteinuria despite maximally tolerated supportive therapy.

Who should consider this trial

Good fit: Ideal candidates are people with primary IgA nephropathy confirmed by kidney biopsy within five years, eGFR ≥45 mL/min/1.73 m2, and persistent proteinuria despite supportive therapy.

Not a fit: People with secondary forms of IgAN, IgA vasculitis, other chronic kidney or urinary tract diseases, very low total IgG, or eGFR below the required cutoff are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, zigakibart could reduce proteinuria and slow loss of kidney function in people with IgA nephropathy.

How similar studies have performed: Early clinical work targeting APRIL and related B-cell pathways has shown promise for reducing proteinuria in IgAN, but larger confirmatory trials are still needed.

Eligibility criteria

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
* Untreated hypertension or uncontrolled hypertension despite treatment (i.e., resistant hypertension)
* 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.

Where this trial is running

Denver, Colorado and 7 other locations

• Colorado Kidney Care Nephrology — Denver, Colorado, United States (RECRUITING)
• American Clinical Trials — Acworth, Georgia, United States (RECRUITING)
• Inter Med Consultants — Edina, Minnesota, United States (RECRUITING)
• Novartis Investigative Site — Shanghai, China (RECRUITING)
• Novartis Investigative Site — Kawasaki, Kanagawa, Japan (RECRUITING)
• Novartis Investigative Site — Miyazaki, Japan (RECRUITING)
• Novartis Investigative Site — Seoul, Korea, South Korea (RECRUITING)
• Novartis Investigative Site — Taipei, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions: Immunoglobulin A Nephropathy, zigakibart, FUB523, anit-APRIL, SHIFT, IgA nephropathy, IgAN, proteinuria