Trial to Evaluate the Long-term Safety and Efficacy of Avacopan in participants With ANCA-associated Vasculitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Jul 2025 → ongoing

Decision date (initial)

2024-09-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-503184-42-00

WHO UTN

U1111-1288-6579

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the long-term safety of avacopan in participants with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)

Secondary objectives 2

1. To evaluate the long-term maintenance of remission with avacopan after month 12 in participants with AAV
2. To evaluate the effect of avacopan on health-related quality of life and other aspects including renal function

Conditions and MedDRA coding

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002023-PIP01-16

Plan to share IPD

Yes

IPD plan description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant has provided informed consent before initiation of any study-specific activities/procedures.
2. 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
3. Age ≥18 years (or ≥ legal age within the country if it is older than 18 years).
4. Positive test for anti-PR3 or anti-MPO (current or historic) antibodies.
5. At least 1 BVAS major item, or at least 3 BVAS nonmajor items, or at least the 2 renal items of proteinuria and hematuria.
6. eGFR ≥ 15 mL/min/1.73 m2 (using Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations).

Exclusion criteria 19

1. Alveolar hemorrhage requiring invasive pulmonary ventilation support anticipated to last beyond the screening period.
2. History of non-TB mycobacteria, opportunistic infections, without appropriate standard course of therapy meeting local guidelines.
3. White blood cell count < 3500/µL, neutrophil count < 1500/µL, or lymphocyte count < 500/µL.
4. Evidence of clinically significant hepatic disease
5. Taking a strong/moderate inducer of the cytochrome P450 3A4 enzyme unless the strong/moderate CYP3A4 inducer can be changed to an alternative medicine.
6. 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
7. 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
8. Female participants with a positive pregnancy test assessed at screening and/or day 1 before randomization by a highly sensitive serum/urine pregnancy test
9. 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.
10. 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.
11. 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.
12. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase>2.0 x the upper limit of normal.
13. Total bilirubin > 1.5 x the ULN. Note: a participant with documented Gilbert's syndrome with total bilirubin < 2 x ULN may be eligible
14. 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
15. Any known multisystem autoimmune disease.
16. Any medical condition requiring or expected to require use of immunosuppressive treatments, including corticosteroids that may cause confoundment with study assessments and conclusions.
17. Had a kidney transplant.
18. Acute/chronic, active hepatitis B virus or hepatitis C virus, or human immunodeficiency virus infection during screening
19. Positive test for active or latent tuberculosis during screening defined as: Positive QuantiFERON or T-SPOT test

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 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.
2. AEs of special interest include: • Hepatic events and drug-induced liver injury (DILI) • Serious hypersensitivity reactions • Serious infections
3. 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

Secondary endpoints 4

1. 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
2. • 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
3. • 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
4. • 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 4

Locations

7 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 69 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications