A Study to Evaluate Avacopan in Participants With ANCA-associated Vasculitis

Sponsor

Amgen (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06072482

Collaborator

(none)

300

Enrollment

Arms

91.8

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the long-term safety of avacopan in participants with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Condition or Disease	Intervention/Treatment	Phase
Antineutrophil Cytoplasmic Antibody-associated Vasculitis	Drug: Avacopan Drug: Placebo Drug: Standard of Care	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled Phase 4 Clinical Trial to Evaluate the Long-term Safety and Efficacy of Avacopan in Subjects With Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

Anticipated Study Start Date :

Dec 12, 2023

Anticipated Primary Completion Date :

Aug 6, 2031

Anticipated Study Completion Date :

Aug 6, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: Avacopan + Standard of Care (SoC) Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.	Drug: Avacopan Administered orally. Other Names: CCX168 Drug: Standard of Care All participants will receive SoC background immunosuppressive therapy for induction and maintenance, at the discretion of the Investigator and as supported by current guidelines, product labels and local practices and informed by the individual participant's clinical condition, preferences, and values.
Experimental: Group B: Avacopan/Placebo + SoC Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.	Drug: Avacopan Administered orally. Other Names: CCX168 Drug: Placebo Administered orally. Drug: Standard of Care All participants will receive SoC background immunosuppressive therapy for induction and maintenance, at the discretion of the Investigator and as supported by current guidelines, product labels and local practices and informed by the individual participant's clinical condition, preferences, and values.
Placebo Comparator: Group C: Placebo + SoC Placebo twice daily for 5 years + SoC background immunosuppressive therapy.	Drug: Placebo Administered orally. Drug: Standard of Care All participants will receive SoC background immunosuppressive therapy for induction and maintenance, at the discretion of the Investigator and as supported by current guidelines, product labels and local practices and informed by the individual participant's clinical condition, preferences, and values.

Arm

Intervention/Treatment

Experimental: Group A: Avacopan + Standard of Care (SoC)

Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.

Drug: Avacopan

Administered orally.

Other Names:

CCX168

Drug: Standard of Care

All participants will receive SoC background immunosuppressive therapy for induction and maintenance, at the discretion of the Investigator and as supported by current guidelines, product labels and local practices and informed by the individual participant's clinical condition, preferences, and values.

Experimental: Group B: Avacopan/Placebo + SoC

Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.

Drug: Avacopan

Administered orally.

Other Names:

CCX168

Drug: Placebo

Administered orally.

Drug: Standard of Care

Placebo Comparator: Group C: Placebo + SoC

Placebo twice daily for 5 years + SoC background immunosuppressive therapy.

Drug: Placebo

Administered orally.

Drug: Standard of Care

Outcome Measures

Primary Outcome Measures

Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [Up to Month 60]
Percentage of Participants Experiencing Adverse Events of Special Interest [Up to Month 60]
Percentage of Participants Experiencing Serious Adverse Events [Up to Month 60]
Percentage of Participants Experiencing Adverse Events Leading to Withdrawal [Up to Month 60]
Percentage of Participants Experiencing Adverse Events Leading to Death [Up to Month 60]
Number of Participants Experiencing Clinical Significant Changes from Baseline in Vital Signs Measurements [Up to Month 60]
Number of Participants Experiencing Clinical Significant Changes from Baseline in Hematology Assessments [Up to Month 60]
Number of Participants Experiencing Clinical Significant Changes from Baseline in Serum Chemistry Assessments [Up to Month 60]
Number of Participants Experiencing Clinical Significant Changes from Baseline in Urinalysis Assessments [Up to Month 60]

Secondary Outcome Measures

Group A and B Participants who Achieved Remission at Month 12: Time to Relapse in AAV Between Month 12 and Month 60 [Month 12 to Month 60]
Group A and B Participants who Achieved Remission at Month 12: Percentage of Participants who Relapse After Achieving Remission at Month 12 [Month 12 to Month 60]
Groups A and C: Percentage of Participants who Achieved Sustained Remission at Month 60 [Month 60]
Group A and C Participants with Overt Renal Disease at Baseline: Change from Baseline to Month 60 in Estimated Glomerular Filtration Rate (eGFR) [Baseline and Month 60]
Groups A and C: Change from Baseline to Month 60 in Short Form 36 Health Survey Version 2 (SF-36 v2) General Health Perception Score [Baseline and Month 60]
Groups A and C: Change from Baseline to Month 60 in EuroQoL-5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) [Baseline and Month 60]
Percentage of Participants who Achieved Remission at Month 6 [Month 6]
Groups A and C: Change from Baseline to Week 60 in Vasculitis Damage Index (VDI) [Baseline and Week 60]
Groups A and C: Percentage of Participants with Composite Outcome of Initiation of Maintenance Dialysis, Kidney Transplantation, or Death [Up to Month 60]
Percentage of Participants With Glucocorticoid Use [Up to Month 60]
Percentage of Participants With Immunosuppressant Use [Up to Month 60]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants has provided informed consent before initiation of any study-specific activities/procedures.
Newly diagnosed or relapse of granulomatosis with polyangiitis or microscopic polyangiitis, consistent with Chapel-Hill Consensus Conference definitions (Jennette et al, 2013), where treatment with cyclophosphamide or rituximab is needed.
Age >/= 18 years (or >/= legal age within the country if it is older than 18 years).
Positive test for anti-positive antiproteinase 3 or antimyeloperoxidase (current or historic) antibodies.
At least 1 Birmingham Vasculitis Activity Score (BVAS) major item, at least 3 BVAS nonmajor items, or at least the 2 renal items of proteinuria and hematuria.
eGFR 15 mL/min/1.73 m^2 (using Chronic Kidney Disease Epidemiology Collaboration equations).

Exclusion Criteria

Alveolar hemorrhage requiring invasive pulmonary ventilation support anticipated to last beyond the screening period of the study.
Any other known multisystem autoimmune disease including eosinophilic granulomatosis with polyangiitis (Churg-Strauss), systemic lupus erythematosus, immunoglobulin A vasculitis (Henoch-Schönlein), rheumatoid vasculitis, Sjogren's syndrome, anti-glomerular basement membrane disease, or cryoglobulinemic vasculitis.
Any medical condition requiring or expected to require continued use of immunosuppressive therapies, including corticosteroids that may cause confoundment with study assessments and study conclusions.
Received dialysis or plasma exchange within 12 weeks before signing of the informed consent.
Have had a kidney transplant.
Malignancy except nonmelanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years before signing the informed consent.
Acute or chronic, active hepatitis B virus or hepatitis C virus, or human immunodeficiency virus infection during screening.
Positive test for active or latent tuberculosis during screening.
White blood cell count < 3500/µL, neutrophil count < 1500/µL, or lymphocyte count < 500/µl.
Evidence of clinically significant hepatic disease including prior diagnosis of cirrhosis.
aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase >2.0 times the upper limit of normal (ULN).
Total bilirubin > 1.5 times the ULN. A participant with documented Gilbert's syndrome with total bilirubin < 2 x ULN may be eligible.
Active infection and/or infection requiring oral or intravenous (IV) antimicrobials within 4 weeks before signing of the informed consent.
History of any clinically significant cardiovascular disease, such as symptomatic congestive heart failure, unstable angina, myocardial infarction or stroke, within 12 weeks before signing of the informed consent.
Received cyclophosphamide (CYC) within 12 weeks before signing the informed consent; if on azathioprine, mycophenolate, or methotrexate at the time of screening, these drugs must be withdrawn before receiving the CYC or rituximab (RTX).
Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone equivalent for more than 6 weeks continuously before signing of the informed consent.
Received RTX or other B-cell depleting therapies within 52 weeks before signing of the informed consent or within 26 weeks before signing of the informed consent provided CD19 count > 0.01x10^9/L, or received any of the following within 12 weeks before signing the informed consent:
antitumor necrosis factor treatment
abatacept
alemtuzumab
IV immunoglobulin
belimumab
tocilizumab.
Taking a strong or moderate inducer of the cytochrome P450 3A4 (CYP3A4) enzyme unless the strong or moderate CYP3A4 inducer can be changed to an alternative medicine at least 1 week before Day 1.
Received an investigational drug within 30 days or within 5 half-lives (whichever is longer) before signing of the informed consent.
Previously received avacopan without clinical benefit per the Investigator's opinion or received avacopan within 60 days before signing of the informed consent.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Amgen

Investigators

Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

AmgenTrials clinical trials website

Publications

None provided.

Responsible Party:

Amgen

ClinicalTrials.gov Identifier:

NCT06072482

Other Study ID Numbers:

20220159
EU CT Number

First Posted:

Oct 10, 2023

Last Update Posted:

Oct 10, 2023

Last Verified:

Oct 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Amgen

Avacopan

ANCA-associated Vasculitis

AAV

Additional relevant MeSH terms:

Vasculitis

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Study Results

No Results Posted as of Oct 10, 2023