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

Primary Purpose

Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Avacopan
Placebo
Standard of Care
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Antineutrophil Cytoplasmic Antibody-associated Vasculitis focused on measuring Avacopan, ANCA-associated Vasculitis, AAV

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Group A: Avacopan + Standard of Care (SoC)

    Group B: Avacopan/Placebo + SoC

    Group C: Placebo + SoC

    Arm Description

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

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

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

    Outcomes

    Primary Outcome Measures

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

    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
    Group A and B Participants who Achieved Remission at Month 12: Percentage of Participants who Relapse After Achieving Remission at Month 12
    Groups A and C: Percentage of Participants who Achieved Sustained Remission at 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)
    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
    Groups A and C: Change from Baseline to Month 60 in EuroQoL-5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
    Percentage of Participants who Achieved Remission at Month 6
    Groups A and C: Change from Baseline to Week 60 in Vasculitis Damage Index (VDI)
    Groups A and C: Percentage of Participants with Composite Outcome of Initiation of Maintenance Dialysis, Kidney Transplantation, or Death
    Percentage of Participants With Glucocorticoid Use
    Percentage of Participants With Immunosuppressant Use

    Full Information

    First Posted
    October 2, 2023
    Last Updated
    October 6, 2023
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06072482
    Brief Title
    A Study to Evaluate Avacopan in Participants With ANCA-associated Vasculitis
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 12, 2023 (Anticipated)
    Primary Completion Date
    August 6, 2031 (Anticipated)
    Study Completion Date
    August 6, 2031 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. 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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Antineutrophil Cytoplasmic Antibody-associated Vasculitis
    Keywords
    Avacopan, ANCA-associated Vasculitis, AAV

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    300 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group A: Avacopan + Standard of Care (SoC)
    Arm Type
    Experimental
    Arm Description
    Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.
    Arm Title
    Group B: Avacopan/Placebo + SoC
    Arm Type
    Experimental
    Arm Description
    Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.
    Arm Title
    Group C: Placebo + SoC
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo twice daily for 5 years + SoC background immunosuppressive therapy.
    Intervention Type
    Drug
    Intervention Name(s)
    Avacopan
    Other Intervention Name(s)
    CCX168
    Intervention Description
    Administered orally.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Administered orally.
    Intervention Type
    Drug
    Intervention Name(s)
    Standard of Care
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
    Time Frame
    Up to Month 60
    Title
    Percentage of Participants Experiencing Adverse Events of Special Interest
    Time Frame
    Up to Month 60
    Title
    Percentage of Participants Experiencing Serious Adverse Events
    Time Frame
    Up to Month 60
    Title
    Percentage of Participants Experiencing Adverse Events Leading to Withdrawal
    Time Frame
    Up to Month 60
    Title
    Percentage of Participants Experiencing Adverse Events Leading to Death
    Time Frame
    Up to Month 60
    Title
    Number of Participants Experiencing Clinical Significant Changes from Baseline in Vital Signs Measurements
    Time Frame
    Up to Month 60
    Title
    Number of Participants Experiencing Clinical Significant Changes from Baseline in Hematology Assessments
    Time Frame
    Up to Month 60
    Title
    Number of Participants Experiencing Clinical Significant Changes from Baseline in Serum Chemistry Assessments
    Time Frame
    Up to Month 60
    Title
    Number of Participants Experiencing Clinical Significant Changes from Baseline in Urinalysis Assessments
    Time Frame
    Up to Month 60
    Secondary Outcome Measure Information:
    Title
    Group A and B Participants who Achieved Remission at Month 12: Time to Relapse in AAV Between Month 12 and Month 60
    Time Frame
    Month 12 to Month 60
    Title
    Group A and B Participants who Achieved Remission at Month 12: Percentage of Participants who Relapse After Achieving Remission at Month 12
    Time Frame
    Month 12 to Month 60
    Title
    Groups A and C: Percentage of Participants who Achieved Sustained Remission at Month 60
    Time Frame
    Month 60
    Title
    Group A and C Participants with Overt Renal Disease at Baseline: Change from Baseline to Month 60 in Estimated Glomerular Filtration Rate (eGFR)
    Time Frame
    Baseline and Month 60
    Title
    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
    Time Frame
    Baseline and Month 60
    Title
    Groups A and C: Change from Baseline to Month 60 in EuroQoL-5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)
    Time Frame
    Baseline and Month 60
    Title
    Percentage of Participants who Achieved Remission at Month 6
    Time Frame
    Month 6
    Title
    Groups A and C: Change from Baseline to Week 60 in Vasculitis Damage Index (VDI)
    Time Frame
    Baseline and Week 60
    Title
    Groups A and C: Percentage of Participants with Composite Outcome of Initiation of Maintenance Dialysis, Kidney Transplantation, or Death
    Time Frame
    Up to Month 60
    Title
    Percentage of Participants With Glucocorticoid Use
    Time Frame
    Up to Month 60
    Title
    Percentage of Participants With Immunosuppressant Use
    Time Frame
    Up to Month 60

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    100 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Amgen Call Center
    Phone
    866-572-6436
    Email
    medinfo@amgen.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
    IPD Sharing Time Frame
    Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
    IPD Sharing Access Criteria
    Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
    IPD Sharing URL
    http://www.amgen.com/datasharing
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website

    Learn more about this trial

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

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