Long-term safety and tolerability of zigakibart in adults with primary IgA nephropathy: an open-label extension study

Trial ID: 2024-519638-22-00
Protocol: CFUB523A12302B
Sponsor: Novartis Pharma AG

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Diseases & Conditions

IgA nephropathy

Objectives

The primary objective of this study is to evaluate the long-term safety and tolerability of zigakibart in adults with IgA nephropathy. This assessment is clinically relevant for determining the prolonged risk profile and patient endurance of the therapeutic agent during continuous administration.

The secondary objectives include:

Evaluation of the effect of zigakibart on proteinuria.
Evaluation of the effect of zigakibart on the estimated glomerular filtration rate (eGFR).
Characterization of the pharmacokinetics, pharmacodynamics, and immunogenicity of zigakibart.
Further assessment of the safety and tolerability of zigakibart.

Participants

This clinical trial involves a total of 151 participants diagnosed with IgA nephropathy. The study population consists of both male and female patients, including vulnerable individuals. The participants are within the age ranges corresponding to pediatric and adolescent groups. Inclusion requires the completion of a preceding parent study involving both the investigational product and a placebo. Eligible subjects must provide signed informed consent and meet the investigator's clinical judgment regarding the potential benefit of receiving open-label zigakibart 600 mg subcutaneous every two weeks. The primary objective is to evaluate the long-term safety and tolerability of the intervention.

Plans and Procedures

This multicenter, open-label extension study is designed to evaluate the long-term safety and tolerability of zigakibart in adults diagnosed with IgA nephropathy. The research methodology involves the administration of 600 mg of zigakibart via subcutaneous injection every two weeks. Eligible participants must have completed a preceding parent study involving either the investigational product or a placebo. The primary objectives are to assess the type, incidence, severity, and seriousness of treatment-emergent adverse events and adverse events of special interest. Secondary endpoints include monitoring changes in the urinary protein-to-creatinine ratio, the estimated glomerular filtration rate, serum concentrations of the drug, immunoglobulin levels, and the presence of anti-drug antibodies. The study duration is estimated to continue through early 2033. Participants may be subject to early termination based on the investigator's clinical judgment.

Treatment

The experimental medication is zigakibart (Bion 1301/FUB523), which is provided as a solution for injection. The administered dose is 600 mg via subcutaneous injection. This substance is classified as an orphan drug.

Efficacy

Efficacy assessment in this study involves the measurement of several secondary endpoints. Changes from baseline to weeks 48 and 96 in the urinary protein-to-creatinine ratio (UPCR) will be evaluated using 24-hour urine collection. The estimated glomerular filtration rate (eGFR) will be assessed at week 96 using the chronic kidney disease-epidemiology collaboration (CKD-EPI) creatinine equation, including the change from the parent study baseline to week 96 of the open-label extension.

Additional efficacy evaluations include:

Serum concentrations of zigakibart.
Changes from baseline in immunoglobulin levels.
Presence of circulating binding and neutralizing antidrug antibodies (ADA/Nab).

Inclusion and Exclusion Criteria

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Inclusion Criteria

Signed informed consent must be obtained prior to participation in the OLE study.
Completion of the parent study (both participants assigned to receive the investigational product and placebo) as defined by the respective protocol
Per Investigator’s clinical judgment, the participant may benefit from receiving open-label treatment of zigakibart 600 mg s.c. Q2W.

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Exclusion Criteria

Participants who prematurely withdrew from zigakibart parent studies in IgAN for any reason
Participants who at the time of first study treatment administration in the OLE are receiving chronic dialysis (≥ 30 days) or who require kidney transplantation.
Acute kidney injury (AKI), defined by AKIN criteria (Mehta et al 2007) within 4 weeks of first study treatment administration in the OLE study.
Clinical suspicion or diagnosis of rapidly progressive glomerulonephritis (RPGN), defined by KDIGO guidelines, or another glomerulopathy at the time of first study treatment administration in the OLE study.
Received a live vaccination within 12 weeks prior to first study treatment administration in the OLE study or plan to have a live vaccination within 6 months after the last dose of study treatment.
Use of systemic corticosteroid therapy (including budesonide) or other immunosuppressive therapy such as but not limited to mycophenolate, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, etc., and herbs such as Tripterygium Wilfordii Hook F, Caulis sinomenii, and Sinomenium acutum for > 2 weeks in the 12 weeks prior to first study treatment administration in the OLE study; use of rituximab within 180-days of first study treatment administration in the OLE study.
Current severe infection at the time of first study treatment in the OLE study or history of recurrent, severe, infections as determined by the Investigator.
Newly diagnosed positive serology for hepatitis A virus IgM antibodies (anti-HAV IgM), hepatitis B surface antigen (HBsAg), detectable hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) antibodies (participants who completed treatment and are persistently antibody positive but have documentation of negative HCV polymerase chain reaction [PCR] will be allowed), or antibodies to HIV-1 and/or HIV-2.
Newly diagnosed malignancy (participants with basal cell carcinoma that was completely resected or curatively treated cervical carcinoma in situ or low-risk prostate cancer (i.e., Gleason score < 7 and prostate specific antigen < 10 ng/mL) are eligible for the study).
Pregnancy or breastfeeding or intent to become pregnant or to donate sperm during the study period and until 24 weeks after last dose.
History or evidence of any other clinically significant medical or psychiatric disorder, condition, disease, or laboratory finding that, in the discretion of the Investigator, constitutes an uncertain or unfavorable benefit-risk for continued long-term therapy with zigakibart.
Confirmed IgG levels < 3 g/L prior to first study treatment administration in the OLE study.
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, from menarche until becoming post-menopausal unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for 24 weeks after stopping study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms).
Sexually active males unwilling to use a highly effective methods of contraception during intercourse while taking study treatment and for 24 weeks after stopping study treatment. In addition, male participants must not donate sperm for the time period specified above.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Yet Recruiting	11 Aug 2026	15
Croatia	Not Yet Recruiting	11 Aug 2026	5
Czechia	Not Yet Recruiting	11 Aug 2026	3
France	Not Yet Recruiting	11 Aug 2026	8
Germany	Not Yet Recruiting	11 Aug 2026	10
Greece	Not Yet Recruiting	11 Aug 2026	6
Italy	Not Yet Recruiting	11 Aug 2026	14
Spain	Not Yet Recruiting	11 Aug 2026	8