Evaluation of Atacicept for Safety and Efficacy in Patients with Multiple Autoimmune Glomerular Diseases: A Phase 2 Clinical Trial

The primary objective of this study is to evaluate the **safety** and **tolerability** of atacicept in patients with multiple autoimmune glomerular diseases. Additionally, the study aims to assess the effect of atacicept on the change from baseline in **proteinuria**. These objectives are clinically relevant as they address the potential of atacicept to provide a therapeutic benefit while ensuring patient safety, which is crucial in the management of autoimmune glomerular diseases.

Secondary objectives include:

• Evaluating the effect of atacicept on change from baseline in estimated **eGFR** (estimated glomerular filtration rate), which is important for understanding the impact on kidney function.
• Assessing the effect of atacicept on change in anti-PLA2R antibodies (pMN) and Gd-IgA1 (IgAN/IgAVN), which are markers associated with specific glomerular diseases.
• Evaluating the **pharmacokinetics** of atacicept to understand its absorption, distribution, metabolism, and excretion.
• Assessing the effect of atacicept on achieving proteinuria response thresholds, which is significant for evaluating its efficacy in reducing proteinuria levels.

The clinical trial involves a total of **112 participants** diagnosed with **Multiple Autoimmune Glomerular Diseases**. The study population includes both male and female subjects, with an age range that encompasses children, adolescents, and adults. Participants were selected based on their stable prescribed standard of care treatment regimen, as well as specific health criteria such as maintaining a systolic blood pressure of ≤160 mmHg and a diastolic blood pressure of ≤90 mmHg at screening. Additionally, participants are required to have a minimum weight of 40 kg. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Lifestyle factors such as diet and physical activity are not specified, but participants must comply with contraceptive guidelines as outlined in the protocol. The selection criteria ensure that the study population is representative of individuals with the condition under investigation, while also maintaining a focus on safety and ethical standards.

The clinical trial is designed to evaluate the **safety** and efficacy of **atacicept** in patients with **multiple autoimmune glomerular diseases**. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to last until December 2027, with recruitment starting in September 2025. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as stable prescribed standard of care treatment, blood pressure, and weight requirements. Participants will be required to comply with contraceptive guidelines as part of the inclusion criteria.

Following the screening, participants will be randomized to receive either the investigational product, **atacicept**, administered as a **subcutaneous injection** in a pre-filled syringe, or a control. The primary endpoint is the change from baseline in urine protein-to-creatinine ratio (UPCR) at Week 36. Secondary endpoints include changes in specific biomarkers and estimated glomerular filtration rate (eGFR) at various time points, as well as the serum concentration of **atacicept** throughout the study. Participants will attend follow-up visits at specified intervals to monitor these parameters and assess the drug's efficacy and safety.

The expected length of participant involvement is up to 52 weeks, with the possibility of early termination if adverse events occur or if the participant fails to adhere to the study protocol. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the long-term effects of the treatment. The study aims to provide comprehensive data on the therapeutic potential of **atacicept** in treating **multiple autoimmune glomerular diseases**, contributing valuable insights into its clinical application.

The clinical trial involves the administration of **Atacicept**, a protein-based experimental medication, formulated as a **solution for injection in pre-filled syringe**. The pharmaceutical form is specifically designed for **subcutaneous injection**. Atacicept is provided in a pre-filled syringe, utilizing the BD Hypak™ SCF™ system, which includes a glass barrel with a staked needle and a Flurotec stopper. The maximum daily dose of Atacicept is 21.43 mg, with a total maximum dose of 7800 mg over the course of the study. The treatment period extends up to 52 weeks, with dosing schedules determined by the study protocol. Participant compliance is monitored through regular assessments and documentation of dosing adherence.

In this study, Atacicept is the sole investigational product, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized. The trial's primary objective is to evaluate the safety and tolerability of Atacicept, as well as its effect on proteinuria in patients with multiple autoimmune glomerular diseases. The study is conducted under the sponsorship of Vera Therapeutics Inc., and Atacicept is designated as an orphan drug, highlighting its potential significance in treating rare conditions. The administration of Atacicept is carefully monitored to ensure participant safety and to gather comprehensive data on its therapeutic effects.

The efficacy of Atacicept in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in the urine protein-to-creatinine ratio (UPCR) at Week 36. This parameter is crucial for evaluating the drug's impact on proteinuria, a common symptom in autoimmune glomerular diseases.

Secondary endpoints include several additional measures: changes from baseline in Gd-IgA1 for IgA nephropathy (IgAN) or anti-PLA2R for primary membranous nephropathy (pMN), changes from baseline in estimated glomerular filtration rate (eGFR) using the CKD-EPI formula at Weeks 36 and 52, and further changes in UPCR at various timepoints—Week 52 for IgAN cohorts, and Weeks 12, 24, and 52 for pMN and nephrotic syndrome (NS) cohorts. Additionally, the serum concentration of Atacicept will be monitored throughout the study, and the proportion of participants achieving predefined proteinuric responses at Weeks 24, 36, and 52 will be evaluated.

These efficacy parameters will be collected and analyzed at specified intervals to determine the therapeutic effect of Atacicept. The use of validated laboratory tests and clinical assessments will ensure the accuracy and reliability of the data collected during the trial.