Evaluation of Long-term Safety and Efficacy of Avacopan in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis

The primary objective of this clinical trial is to evaluate the long-term **safety** of avacopan in participants with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This is clinically relevant as it aims to ensure that avacopan, a treatment option for AAV, does not pose significant long-term health risks to patients, thereby supporting its use in managing this condition.

Secondary objectives include: - Evaluating the long-term maintenance of remission with avacopan after month 12 in participants with AAV. This is important for understanding the sustained efficacy of avacopan in preventing disease relapse. - Assessing the effect of avacopan on health-related quality of life and other aspects, including renal function. This objective is crucial for determining the broader impact of avacopan on patient well-being and organ function, which are significant considerations in the management of AAV.

The clinical trial involves a total of **60 participants** diagnosed with **antineutrophil cytoplasmic antibody-associated vasculitis (AAV)**. The study population includes both male and female subjects, aged 18 years and older, with no vulnerable populations selected. Participants were chosen based on specific criteria, including a positive test for anti-PR3 or anti-MPO antibodies and a requirement for induction treatment with cyclophosphamide or rituximab. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include having at least one BVAS major item or specific renal items, and an eGFR of at least 15 mL/min/1.73 m². The trial aims to evaluate the long-term safety of avacopan in this patient group.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the long-term safety and efficacy of **avacopan** in participants with **antineutrophil cytoplasmic antibody-associated vasculitis (AAV)**. The trial is categorized as a Phase IV study, focusing on the post-marketing surveillance of the drug. The estimated duration of the trial is from September 2024 to December 2036, with participant involvement expected to last up to 60 months. The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit.

During the **screening visit**, participants will undergo assessments to confirm eligibility based on inclusion criteria such as age, diagnosis of AAV, and renal function. The trial will involve the administration of **Tavneos 10 mg hard capsules** (avacopan) or a placebo, with the primary objective being the evaluation of the drug's safety profile. This will be assessed through the monitoring of treatment-emergent adverse events, serious adverse events, and changes in vital signs and laboratory parameters. Secondary endpoints include the time to relapse and the proportion of participants achieving sustained remission.

Participants will be required to attend regular follow-up visits to monitor their health status and the efficacy of the treatment. These visits will include clinical evaluations, laboratory tests, and assessments of disease activity. The end-of-study visit will conclude the participant's involvement, with a final evaluation of their health status and any long-term effects of the treatment. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, withdrawal of consent, or non-compliance with study procedures.

The trial aims to provide comprehensive data on the long-term safety and efficacy of avacopan in managing AAV, contributing valuable information to the medical community and potentially improving treatment strategies for this condition.

The clinical trial involves the administration of **Avacopan**, marketed as Tavneos 10 mg hard capsules, which is the primary experimental medication. Avacopan is formulated as hard capsules and is administered orally. The maximum daily dose is 60 mg, with a total maximum dose of 21,840 mg over a treatment period of 60 days. This medication is of chemical origin and is specifically designed for pediatric use. The trial aims to evaluate the long-term safety and efficacy of Avacopan in participants with **Antineutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis**.

A placebo, referred to as Placebo for AMG 569, is utilized in the study to maintain the double-blind nature of the trial. The pharmaceutical form and route of administration for the placebo are not specified. The placebo serves as a control to compare the effects of Avacopan.

Several auxiliary treatments are included in the trial, such as **Mycophenolate Mofetil**, which is administered both orally and intravenously. The pharmaceutical form is denoted as PHF00170MIG. The maximum daily and total doses are unspecified, but the treatment period is limited to one day.

**Rituximab** is another auxiliary treatment, administered intravenously. It is formulated as PHF00230MIG, with unspecified maximum daily and total doses, and a treatment period of one day.

**Azathioprine** is included as an auxiliary treatment, available for oral and intravenous administration. The pharmaceutical form is PHF00170MIG, with unspecified dosing limits and a one-day treatment period.

**Cyclophosphamide** is administered intravenously as part of the auxiliary treatments. It is formulated as PHF00231MIG, with unspecified maximum daily and total doses, and a treatment period of one day.

**Methotrexate Sodium** is also used as an auxiliary treatment, administered both orally and intravenously. The pharmaceutical form is PHF00245MIG, with unspecified dosing limits and a one-day treatment period.

**Glucocorticoids** for systemic use are included as a non-experimental treatment, administered orally and intravenously. The pharmaceutical form is PHF00231MIG, with unspecified maximum daily and total doses, and a treatment period of one day.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial is designed to assess the safety and efficacy of Avacopan in comparison to the placebo and auxiliary treatments in managing ANCA-associated vasculitis.

The efficacy of avacopan in participants with **Antineutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis** will be assessed through several secondary endpoints. These include the time to relapse in ANCA-associated vasculitis between month 12 and month 60 among participants who achieved remission at month 12, comparing group A with group B. Additionally, the proportion of participants who relapse after achieving remission at month 12 in group A compared with group B, and the proportion of participants who achieved sustained remission at month 60 in group A compared with group C will be evaluated.

Further efficacy assessments will involve changes from baseline to month 60 in various parameters, such as the estimated glomerular filtration rate (eGFR) of participants with overt renal disease at baseline, the SF-36 v2 General Health Perception score, the EQ 5D-5L visual analogue scale, and the Vasculitis Damage Index (VDI), all comparing group A with group C. The proportion of participants who achieved remission at month 6 in groups A + B compared with group C will also be measured. Additionally, the composite outcome of initiation of maintenance dialysis, kidney transplantation, or death in group A compared with group C from baseline to month 60 will be assessed, along with glucocorticoid and immunosuppressant use.