Phase 2 Open‑Label Study of Subcutaneous Surovatamig (AZD0486) in Adults with Antibody‑Mediated Kidney Disease: Safety, Tolerability, PK and Proteinuria Efficacy

Primary objective is to evaluate the safety and tolerability of surovatamig and its impact on proteinuria in adults with antibody-mediated kidney disease. Safety assessment will determine the incidence and severity of adverse events, providing a risk–benefit profile, while reduction in proteinuria serves as a surrogate marker of disease activity and renal prognosis.

Secondary objectives include:

• Proportion of participants achieving partial or complete remission at 24 months.
• Effect of surovatamig on proteinuria.
• Quantification of anti‑PLA2R antibodies in serum.
• Assessment of B‑cell depletion in peripheral blood.
• Time to relapse after attaining remission.
• Time to a sustained reduction in estimated glomerular filtration rate from baseline.
• Change in patient‑reported experience.
• Characterisation of the pharmacokinetic profile of surovatamig.
• Evaluation of the immunogenicity of surovatamig.

Seventeen participants (male and female, inclusive of all gender identities) aged 18 to 75 years were enrolled. All were patients with anti-PLA2R antibody‑positive primary membranous nephropathy, classified as antibody‑mediated kidney disease according to KDIGO 2021 guidelines. Enrollment required prior receipt of standard‑of‑care therapy with an ACE inhibitor or angiotensin receptor blocker for at least four weeks, unless intolerance or contraindication existed. Additional health criteria included an estimated glomerular filtration rate meeting the protocol minimum, adequate hematologic function, and specified minimum levels of CD19⁺ B cells and IgG at screening. Participants were required to use contraception consistent with local regulations, and vulnerable individuals were permitted to enroll. Selection was based on these inclusion criteria without further specification of exclusion criteria.

The study is a Phase 2, open-label investigation of subcutaneous surovatamig in adults with Antibody-mediated Kidney Disease. After an initial screening visit to confirm eligibility (including anti‑PLA2R positivity, eGFR, CD19+ B‑cell count and IgG levels), participants receive a baseline dose and commence a 24‑month treatment period. Follow‑up visits are scheduled at regular intervals (e.g., monthly for safety assessments, PK sampling at predefined time points, and efficacy evaluations at 6, 12 and 24 months). The primary endpoints include incidence and severity of adverse events and the change from baseline in UPCR at 6 months; secondary endpoints assess remission rates, antibody titers, B‑cell counts, renal function, patient‑reported outcomes, PK parameters and anti‑drug antibodies. Expected participant involvement spans the screening period plus the 24‑month treatment and observation phase. Early termination may occur for significant safety concerns (e.g., serious adverse events), protocol non‑compliance, withdrawal of consent, or loss to follow‑up.

The investigational product identified as AZD0486 is supplied as a solution for injection for subcutaneous administration. One formulation contains a human IgG4 kappa monoclonal antibody against CD3 and CD19; the dose specified in the protocol is 0 mg per administration, delivered via the subcutaneous route. The dosing frequency is not explicitly defined in the source data and will follow the schedule outlined in the study protocol.

A second formulation of surovatamig is also provided under the designation AZD0486 and is presented as a solution for injection intended for subcutaneous delivery. The protocol lists a dose of 0 mg per administration, with the route of administration being subcutaneous. Frequency of dosing will be determined according to the protocol‑specified regimen.

No additional non‑experimental comparators, such as standard‑of‑care therapy or placebo, are described for this study. All investigational administrations are performed by qualified personnel, and compliance is monitored through documented dosing logs, verification of injection sites, and periodic assessment of drug accountability. Adherence to the dosing schedule is reinforced by scheduled study visits and direct observation of each subcutaneous injection.

Efficacy assessments will focus on quantitative changes in proteinuria, serologic markers, cellular biomarkers, and clinical outcomes. The primary efficacy parameter is the change from baseline in the urine protein‑to‑creatinine ratio (UPCR) measured from a 24‑hour urine collection at 6 months. Secondary efficacy parameters include the proportion of participants achieving complete or partial remission of primary membranous nephropathy (complete remission and partial remission) at 24 months, change from baseline in UPCR at 24 months, change in anti‑PLA2R antibody titer, change in peripheral blood B‑cell count, time to relapse after remission, time to a sustained ≥3‑month reduction in eGFR, and change in patient‑reported outcomes.

Proteinuria will be quantified using standardized 24‑hour urine collections, with UPCR calculated in grams per 24 h. Anti‑PLA2R antibody titers and B‑cell counts will be measured using validated laboratory assays on peripheral blood samples. Patient‑reported outcomes will be captured with the study‑specified questionnaire administered at baseline and predefined visits. Remission status will be determined by applying predefined proteinuria thresholds and stable kidney function criteria to the laboratory data.

Assessments will be performed at baseline, 6 months, and 24 months for longitudinal comparisons. Time‑to‑event endpoints (relapse and sustained eGFR decline) will be evaluated continuously up to 24 months using survival analysis methods. All efficacy data will be analyzed using appropriate statistical techniques, including comparison of mean changes from baseline, calculation of remission rates with confidence intervals, and Kaplan‑Meier estimates for time‑dependent outcomes.