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

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.

Overview

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).

Interventions

• Biological zigakibart
  zigakibart 600 mg sc injections every second week for 104 weeks (2 years)

Primary outcome measures

• Change in mesangial IgA deposition [Time frame: Baseline to Week 53 or 105]

Secondary outcome measures (11)

• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Day 1 to Week 118]
• Change in MEST-C score [Time frame: Baseline to Week 53 or 105]
• Change in CD68+ cells in glomeruli and tubulo-interstitial compartment [Time frame: Baseline to Week 53 or 105]
• Change in complement component C3c [Time frame: Baseline to Week 53 or 105]
• Change in UPCR [Time frame: Baseline to Week 53 and 105]
• Change in eGFR [Time frame: Baseline to Week 53 and 105]
• Change in albuminuria [Time frame: Baseline to Week 53 and 105]
• Change in hematuria [Time frame: Baseline to Week 53 and 105]
• Change in serum IgA, IgM and IgG [Time frame: Baseline to Week 13, 29, 53, 79 and 105]
• Serum zigakibart concentrations [Time frame: Baseline, Week 13, 29, 66, 79 and 105]
• Circulating anti-zigakibart antibodies [Time frame: Baseline, Week 13, 29, 66, 79 and 105]

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
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• Colorado Kidney Care Nephrology — Denver
• American Clinical Trials — Acworth
• Univ Of Iowa Hospitals And Clinics — Iowa City
• Inter Med Consultants — Edina

Spain · 4 centers

• Novartis Investigative Site — Pamplona
• Novartis Investigative Site — Valencia
• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Seville

Germany · 3 centers

• Novartis Investigative Site — Munich
• Novartis Investigative Site — Hanover
• Novartis Investigative Site — Mainz

Italy · 3 centers

• Novartis Investigative Site — Ranica
• Novartis Investigative Site — Brescia
• Novartis Investigative Site — Pavia

Brazil · 2 centers

• Novartis Investigative Site — Serra
• Novartis Investigative Site — Botucatu

China · 2 centers

• Novartis Investigative Site — Beijing
• Novartis Investigative Site — Shanghai

Japan · 2 centers

• Novartis Investigative Site — Kawasaki
• Novartis Investigative Site — Miyazaki

Poland · 2 centers

• Novartis Investigative Site — Lodz
• Novartis Investigative Site — Opole

South Korea · 2 centers

• Novartis Investigative Site — Seoul
• Novartis Investigative Site — Seoul

Taiwan · 2 centers

• Novartis Investigative Site — Kaohsiung City
• Novartis Investigative Site — Taipei

Identifiers

NCT: NCT07146906 · CFUB523A12201 · 2024-519699-24 · U1111-1323-5075

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗