AVACOPAN for ANCA-associated vasculitis (AAV) | Granulomatosis with polyangiitis (GPA) | Microscopic polyangiitis (MPA)

Inclusion criteria

• {"criterion_text":"- Participant has provided informed consent before initiation of any study-specific activities/procedures.\n- Newly diagnosed or relapse of GPA or MPA, consistent with Chapel-Hill Consensus Conference definitions (Jennette et al, 2013), where induction treatment with cyclophosphamide or rituximab is needed\n- Age ≥18 years (or ≥ legal age within the country if it is older than 18 years).\n- Positive test for anti-PR3 or anti-MPO (current or historic) antibodies.\n- At least 1 BVAS major item, or at least 3 BVAS nonmajor items, or at least the 2 renal items of proteinuria and hematuria.\n- eGFR ≥ 15 mL/min/1.73 m2 (using Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations)."}

Exclusion criteria

• {"criterion_text":"- Alveolar hemorrhage requiring invasive pulmonary ventilation support anticipated to last beyond the screening period.\n- History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or Amgen physician if consulted, would pose a risk to participant safety/ interfere with the study evaluation, procedures, or completion.\n- Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study to the best of the subject and investigator’s knowledge.\n- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase>2.0 x the upper limit of normal.\n- Total bilirubin > 1.5 x the ULN. Note: a participant with documented Gilbert's syndrome with total bilirubin < 2 x ULN may be eligible\n- If before signing the informed consent subject has any of the following: Received dialysis or plasma exchange within 12 weeks Malignancy (except curatively treated nonmelanoma skin cancers, curatively treated cervical carcinoma in situ, or curatively treated breast ductal carcinoma in situ within the last 5 years Active infection, or infection requiring IV anti-infective agents within 4 weeks or completion of oral anti-infective agents within 2 weeks Known COVID-19 positive test within 2 weeks History of any clinically significant cardiovascular disease within 12 weeks Received cyclophosphamide within 12 weeks; if on AZA, mycophenolate, or MTX at the time of screening, these drugs must be withdrawn before receiving the cyclophosphamide or rituximab. Have been taking an oral daily dose of a glucocorticoid of >10 mg prednisone equivalent for more than 6 weeks continuously Received rituximab/B-cell depleting therapies within 26 weeks. Received any of the following within 12 weeks: - antitumor necrosis factor treatment,- abatacept,alemtuzumab,- IV Ig,belimumab,- tocilizumab Note: immunosuppressive drugs not listed here must be discussed with the medical monitor. Received a live, replication-competent vaccine within 6 weeks Received an investigational drug within 30 days or within 5 half-lives (whichever is longer) Previously received avacopan without clinical benefit per investigator’s opinion or received avacopan within 60 days\n- Any known multisystem autoimmune disease.\n- Any medical condition requiring or expected to require use of immunosuppressive treatments, including corticosteroids that may cause confoundment with study assessments and conclusions.\n- Had a kidney transplant.\n- Acute/chronic, active hepatitis B virus or hepatitis C virus, or human immunodeficiency virus infection during screening\n- Positive test for active or latent tuberculosis during screening defined as: Positive QuantiFERON or T-SPOT test\n- History of non-TB mycobacteria, opportunistic infections, without appropriate standard course of therapy meeting local guidelines.\n- White blood cell count < 3500/µL, neutrophil count < 1500/µL, or lymphocyte count < 500/µL.\n- Evidence of clinically significant hepatic disease\n- Taking a strong/moderate inducer of the cytochrome P450 3A4 enzyme unless the strong/moderate CYP3A4 inducer can be changed to an alternative medicine.\n- Female participants of childbearing potential unwilling to use protocol-specified contraception during treatment and for at least 60 days after last dose of avacopan/placebo\n- Female participants who are breastfeeding, who plan to breastfeed, or who are planning to become pregnant while on study, through to 60 days after the last dose of avacopan/placebo\n- Female participants with a positive pregnancy test assessed at screening and/or day 1 before randomization by a highly sensitive serum/urine pregnancy test\n- Any contraindication, including known hypersensitivity to avacopan or any of the protocol-required therapies to be administered during dosing, in alignment with the local product information of those therapies."}

Primary endpoints

• {"endpoint_text":"- Evaluation of the overall safety of avacopan, based on reported treatment-emergent adverse events (AEs), AEs of special interest, SAEs, AEs leading to withdrawal, deaths, and changes from baseline vital signs, hematology, serum chemistry, and urinalysis.","definition_or_measurement_approach":"Overall safety assessed by reported treatment-emergent AEs, AEs of special interest, SAEs, AEs leading to withdrawal, deaths, and changes from baseline in vital signs, hematology, serum chemistry, and urinalysis."}
• {"endpoint_text":"- AEs of special interest include: • Hepatic events and drug-induced liver injury (DILI) • Serious hypersensitivity reactions • Serious infections","definition_or_measurement_approach":"AEs of special interest specifically tracked: hepatic events/DILI, serious hypersensitivity reactions, and serious infections (as reported AEs)."}
• {"endpoint_text":"- Other safety endpoints include: • Infections, based on reported AEs • Creatinine phosphokinase (CPK) increases, based on reported AEs and measured CPK levels • General safety topics including malignancy and major cardiovascular events","definition_or_measurement_approach":"Other safety endpoints include infections (reported AEs), CPK increases (reported AEs and measured CPK laboratory values), and monitoring for malignancy and major cardiovascular events."}

Secondary endpoints

• {"endpoint_text":"- Time to relapse in AAV between month 12 and month 60 among participants who achieved remission at month 12, in group A compared with group B","definition_or_measurement_approach":"Time-to-event analysis of relapse between month 12 and month 60 among participants in remission at month 12, comparing Group A vs Group B."}
• {"endpoint_text":"- • Proportion of participants who relapse after achieving remission at month 12 in group A compared with group B • Proportion of participants who achieved sustained remission at month 60 in group A compared with group C","definition_or_measurement_approach":"Proportion (categorical outcomes) of participants relapsing after month 12 and proportion achieving sustained remission at month 60, compared across specified groups."}
• {"endpoint_text":"- • Change from baseline to month 60 in: - eGFR of participants with overt renal disease at baseline in group A compared with group C - SF-36 v2 General Health Perception score in group A compared with group C - EQ 5D-5L visual analogue scale in group A compared with group C - Vasculitis damage index (VDI) in group A compared with group C • Proportion of participants who achieved remission at month 6 in groups A + B compared with group C","definition_or_measurement_approach":"Continuous and categorical measures comparing change from baseline to month 60 for eGFR, SF-36 v2 general health score, EQ-5D-5L VAS, VDI, and proportion achieving remission at month 6 (groups A+B vs C)."}
• {"endpoint_text":"- • Proportion of participants with composite outcome of initiation of maintenance dialysis, kidney transplantation, or death in group A compared with group C from baseline to month 60 • Glucocorticoid use • Immunosuppressant use","definition_or_measurement_approach":"Composite outcome (initiation of maintenance dialysis, kidney transplant, or death) proportion comparison baseline to month 60; monitoring and summarisation of glucocorticoid and immunosuppressant use."}

Methods

• Physician-to-physician referral letters (Dr to Dr) — recruitment materials present in K2/Recruitment documents.
• Patient-facing materials and Patient Reported Outcome materials — patient information and recruitment materials (multiple languages) are documented.
• Site-based recruitment via participating hospitals/clinics as listed in trial sites (site-specific recruitment procedures documented in K1 recruitment arrangements).

Hungary

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

10-07-2025

Processing Time Days

364

Number Of Sites

2

Number Of Participants

4

Romania

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

15-07-2025

Processing Time Days

407

Number Of Sites

3

Number Of Participants

5

Czechia

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

522

Number Of Sites

7

Number Of Participants

10

Poland

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

666

Number Of Sites

5

Number Of Participants

12

Denmark

Earliest CTIS Part Ii Submission Date

23-02-2026

Latest Decision Or Authorization Date

02-03-2026

Processing Time Days

7

Number Of Sites

3

Number Of Participants

6

France

Earliest CTIS Part Ii Submission Date

25-03-2026

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

19

Number Of Sites

4

Number Of Participants

4

Greece

Earliest CTIS Part Ii Submission Date

17-11-2025

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

112

Number Of Sites

2

Number Of Participants

6

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Suvoda LLC

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central laboratory services","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"University Of Oxford","duties_or_roles":"Investigator BVAS/VDI training","organisation_type":"Educational Institution"}
• {"country":"France","full_name":"Quipment","duties_or_roles":"Equipment and ancillary supplies provider","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}