ANCA-Associated Vasculitis
Conditions
Keywords
ANCA-associated vasculitis, complement, vasculitis, C5aR, avacopan, CCX168, MPA, GPA
Brief summary
The primary objective is to evaluate the efficacy of CCX168 (avacopan) to induce and sustain remission in patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or in combination with rituximab.
Detailed description
Complement 5a and its receptor C5aR (CD88) are involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This is a randomized, double-blind, active-controlled Phase 3 study to evaluate the safety and efficacy of the orally-administered, selective C5aR inhibitor CCX168 (avacopan) in inducing and sustaining remission in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated concomitantly with Rituximab or Cyclophosphamide/Azathioprine. Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
Interventions
DRUGAvacopan
Avacopan 30 mg twice daily orally for 52 weeks (364 days): \- Three 10 mg avacopan capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose. Oral prednisone-matching placebo tapering regimen over 20 weeks (140 days): * Prednisone-matching placebo capsules equivalent to 60 mg per day if the subject's body weight was ≥55 kg, or 45 mg per day if the subject's body weight was \<55 kg, starting on Day 1 with tapering according to a protocol-specified schedule. * Adolescents who weighed ≤37 kg started at a prednisone-matching placebo dose of 30 mg per day.
DRUGPrednisone
Avacopan-matching placebo twice daily orally for 52 weeks (364 days): \- Three avacopan-matching placebo capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose. Oral prednisone tapering regimen over 20 weeks (140 days): * Prednisone 60 mg per day if the subject's body weight was ≥55 kg, or 45 mg per day if the subject's body weight was \<55 kg, starting on Day 1 with tapering according to the protocol-specified schedule. * Adolescents who weighed ≤37 kg started at a prednisone dose of 30 mg per day.
DRUGCyclophosphamide
Orally or intravenously administered
BIOLOGICALRituximab
Intravenously administered
DRUGAzathioprine
Orally administered
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study was double-blind, double-dummy, i.e., placebo capsules were identical in appearance to the avacopan capsules, and prednisone capsules also had matching placebo capsules. To maintain the blind, multiple measures were taken (i.e., randomization code was not accessible to study personnel who had contact with study centers or who were involved in data management and analysis for the duration of the study).
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis * Male and female subjects, aged at least 18 years, with newly-diagnosed or relapsed associated vasculitis (AAV) where treatment with cyclophosphamide or rituximab is needed; where approved by Regulatory Agencies, adolescents (12-17 year old) may be enrolled * Use of adequate contraception * Positive test for anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) * At least 1 major item, or at least 3 non-major items, or at least the 2 renal items of proteinuria and hematuria on Birmingham Vasculitis Activity Score (BVAS) * Estimated glomerular filtration rate ≥15 mL/minute/1.73 m\^2 at screening
Exclusion criteria
* Pregnant or breast-feeding * Alveolar hemorrhage requiring pulmonary ventilation support at screening * Any other known multi-system autoimmune disease * Required dialysis or plasma exchange within 12 weeks prior to screening * Have a kidney transplant * Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1 * Received intravenous glucocorticoids, \>3000 mg methylprednisolone equivalent, within 4 weeks prior to screening * Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening * Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred (i.e., CD19 count \> 0.01x10\^9/L); received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or eculizumab within 12 weeks prior to screening * For patients scheduled to receive cyclophosphamide treatment, urinary outflow obstruction, active infection (especially varicella zoster infection), or platelet count \<50,000/μL before start of dosing * Participated previously in a CCX168 study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Disease Remission at Week 26 | Week 26 | Disease remission at Week 26 was defined as: * Achieving a BVAS of 0 as determined by the Adjudication Committee; * No administration of glucocorticoids given for ANCA-associated vasculitis within 4 weeks prior to Week 26; * No BVAS \>0 during the 4 weeks prior to Week 26 (if collected for an unscheduled assessment). |
| Percentage of Subjects Achieving Sustained Disease Remission at Week 52 | Week 52 | Sustained remission at Week 52 was defined as: * Disease remission at Week 26 as defined above; * Disease remission at Week 52 defined as a BVAS of 0 at Week 52 as determined by the Adjudication Committee and no administration of glucocorticoids for treatment of ANCA-associated vasculitis within 4 weeks prior to Week 52; * No disease relapse between Week 26 and Week 52 as determined by the Adjudication Committee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC | Week 4 | AC=Adjudication Committee; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health). |
| Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | Baseline, Week 26 and 52 | SF-36v2: Measure of health- related quality of life (Medical Outcomes Survey Short Form-36 version 2) EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels The SF-36v2 component scores and the EQ-5D-5L VAS score range from 0 (worst health) to 100 (best health). The EQ-5D-5L Index Score ranges from 0 (worst health) to 1 (best health). |
| Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study | Week 52 | The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: 1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or 2. having achieved BVAS=0 at any time during the treatment period ANCA=anti-neutrophil cytoplasmic autoantibody; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health). |
| Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period | Week 52 | The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: 1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or 2. having achieved BVAS=0 at any time during the treatment period The Birmingham Vasculitis Activity Score (BVAS) form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health). |
| In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks | Baseline, Week 26 and 52 | Change from baseline in kidney function, as measured by eGFR (based on the MDRD equation), was measured in subjects with renal disease based on the BVAS renal component. eGFR=estimated glomerular filtration rate BVAS=Birmingham Vasculitis Activity Score MDRD=Modification of Diet in Renal Disease |
| In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks | Baseline, Week 4, 26 and 52 | BVAS=Birmingham Vasculitis Activity Score UACR=Urinary albumin:creatinine ratio |
| In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks | Baseline, Week 26 and 52 | BVAS=Birmingham Vasculitis Activity Score MCP-1=monocyte chemoattractant protein-1 |
| Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points | Baseline, Week 26 and 52 | VDI=Vasculitis Damage Index; The VDI is comprised of 64 items of damage, grouped into 11 organ-based systems or categorizations. Damage is defined as the presence of non-healing scars and does not give any indication of current disease activity. Damage is also defined as having been present or currently present for at least 3 months. Completion of the form provides a numerical score, which ranges from 0 (best health) to 64 (worst health). |
| Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Baseline, Week 26 and 52 | — |
| Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Baseline, Week 26 and 52 | — |
| Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5) | Baseline, Week 26 and 52 | — |
| Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5) | Baseline, Week 26 and 52 | — |
| Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | From day 1 throughout the study period (day 421/week 60) | AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse event |
| Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Baseline, Week 26 and 52 | — |
| Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Baseline, Week 26 and 52 | — |
| Change From Baseline in Vital Signs (1/5) | Baseline, Week 26 and 52 | — |
| Change From Baseline in Vital Signs (2/5) | Baseline, Week 26 and 52 | — |
| Change From Baseline in Vital Signs (3/5) | Baseline, Week 26 and 52 | — |
| Change From Baseline in Vital Signs (4/5) | Baseline, Week 26 and 52 | — |
| Change From Baseline in Vital Signs (5/5) | Baseline, Week 26 and 52 | BMI=Body Mass Index |
| Number of Subjects With Clinically Significant ECG Changes From Baseline | From day 1 throughout the study period (day 421/week 60) | Clinical significance was assessed by the individual reading of the ECGs ECG=Electrocardiogram |
| Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | From day 1 throughout the study period (day 421/week 60) | AE=Adverse Event |
| Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | From day 1 throughout the study period (day 421/week 60) | WBC=White Blood Cell TEAE=Treatment-Emergent Adverse Event |
| Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study | From day 1 throughout the study period (day 421/week 60) | BVAS=Birmingham Vasculitis Activity Score; A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: 1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or 2. having achieved BVAS=0 at any time during the treatment period The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health). |
| Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5) | Baseline, Week 26 and 52 | — |
| Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | Baseline, Week 13 and 26 | GTI-CWS=Glucocorticoid Toxicity Index Cumulative Worsening Score; GTI-AIS=Glucocorticoid Toxicity Index Aggregate Improvement Score; The Glucocorticoid Toxicity Index (GTI) was developed to score glucocorticoid toxicity. The GTI includes: the Cumulative Worsening Score (CWS) that captures cumulative toxicity, both permanent and transient, over the course of time (serves as a cumulative record of toxicity); and the Aggregate Improvement Score that captures both improvement and worsening of toxicity over time (serves as a record of both improving and worsening toxicity). Both scores range from 0 (best health) to 100 (worst health). |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Ireland, Italy, Japan, Netherlands, New Zealand, Norway, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
A total of 143 study centers randomized at least 1 subject. The target enrollment was 300 subjects.
Pre-assignment details
Screening details: Of 386 subjects screened, 331 were enrolled in the study and randomized to treatment. Reasons for subjects failing screening included not meeting inclusion/exclusion criteria, withdrawal by subject, adverse event (AE) and other.
Participants by arm
| Arm | Count |
|---|---|
| Prednisone Group Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone | 164 |
| Avacopan Group Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo | 166 |
| Total | 330 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 4 | 2 |
| Overall Study | Did not meet eligibility criteria | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 4 | 3 |
| Overall Study | Withdrawal by parent/guardian | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Total | Avacopan Group | Prednisone Group |
|---|---|---|---|
| Age at diagnosis of ANCA-associated Vasculitis | 59.6 years STANDARD_DEVIATION 15.37 | 59.8 years STANDARD_DEVIATION 15.6 | 59.4 years STANDARD_DEVIATION 15.19 |
| Age at screening | 60.9 years STANDARD_DEVIATION 14.51 | 61.2 years STANDARD_DEVIATION 14.56 | 60.5 years STANDARD_DEVIATION 14.5 |
| Age, Customized Adolescents (12-17 years) | 3 Participants | 2 Participants | 1 Participants |
| Age, Customized Adults (18-50 years) | 58 Participants | 30 Participants | 28 Participants |
| Age, Customized Adults (51-64 years) | 109 Participants | 48 Participants | 61 Participants |
| Age, Customized Adults (65-75 years) | 114 Participants | 62 Participants | 52 Participants |
| Age, Customized Adults (>75 years) | 46 Participants | 24 Participants | 22 Participants |
| ANCA-associated vasculitis Status Newly diagnosed | 229 Participants | 115 Participants | 114 Participants |
| ANCA-associated vasculitis Status Relapsed | 101 Participants | 51 Participants | 50 Participants |
| ANCA Positivity Myeloperoxidase (MPO) | 188 Participants | 94 Participants | 94 Participants |
| ANCA Positivity Proteinase 3 (PR3) | 142 Participants | 72 Participants | 70 Participants |
| BMI | 26.75 kilogram(s)/square meter STANDARD_DEVIATION 5.612 | 26.72 kilogram(s)/square meter STANDARD_DEVIATION 5.997 | 26.78 kilogram(s)/square meter STANDARD_DEVIATION 5.212 |
| Body Weight | 77.07 kilogram(s) STANDARD_DEVIATION 19.783 | 76.43 kilogram(s) STANDARD_DEVIATION 20.254 | 77.71 kilogram(s) STANDARD_DEVIATION 19.335 |
| BVAS Components Abdominal | 5 Participants | 4 Participants | 1 Participants |
| BVAS Components Cardiovascular | 9 Participants | 6 Participants | 3 Participants |
| BVAS Components Chest | 142 Participants | 71 Participants | 71 Participants |
| BVAS Components Cutaneous | 47 Participants | 24 Participants | 23 Participants |
| BVAS Components Ear Nose and Throat | 144 Participants | 75 Participants | 69 Participants |
| BVAS Components General | 225 Participants | 111 Participants | 114 Participants |
| BVAS Components Mucous Membranes/Eyes | 66 Participants | 26 Participants | 40 Participants |
| BVAS Components Nervous System | 69 Participants | 38 Participants | 31 Participants |
| BVAS Components Renal + Other (RBC Casts and/or Glomerulonephritis) | 268 Participants | 134 Participants | 134 Participants |
| BVAS Entry Criteria One or more major item | 206 Participants | 104 Participants | 102 Participants |
| BVAS Entry Criteria Three or more minor items | 288 Participants | 146 Participants | 142 Participants |
| BVAS Entry Criteria Two renal items of proteinuria and hematuria | 117 Participants | 60 Participants | 57 Participants |
| BVAS Score | 16.2 units on a scale STANDARD_DEVIATION 5.77 | 16.3 units on a scale STANDARD_DEVIATION 5.87 | 16.2 units on a scale STANDARD_DEVIATION 5.69 |
| Duration of ANCA-Associated Vasculitis | 21.54 months STANDARD_DEVIATION 46.84 | 22.93 months STANDARD_DEVIATION 52.464 | 20.13 months STANDARD_DEVIATION 40.473 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 7 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 308 Participants | 151 Participants | 157 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 8 Participants | 2 Participants |
| Geographic Region Europe and Rest of World excluding Japan | 250 Participants | 121 Participants | 129 Participants |
| Geographic Region Japan | 21 Participants | 11 Participants | 10 Participants |
| Geographic Region North America | 59 Participants | 34 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 32 Participants | 17 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) White | 278 Participants | 138 Participants | 140 Participants |
| Region of Enrollment Australia | 14 participants | 10 participants | 4 participants |
| Region of Enrollment Austria | 6 participants | 3 participants | 3 participants |
| Region of Enrollment Belgium | 10 participants | 6 participants | 4 participants |
| Region of Enrollment Canada | 13 participants | 8 participants | 5 participants |
| Region of Enrollment Czechia | 9 participants | 2 participants | 7 participants |
| Region of Enrollment Denmark | 16 participants | 6 participants | 10 participants |
| Region of Enrollment France | 40 participants | 22 participants | 18 participants |
| Region of Enrollment Germany | 54 participants | 22 participants | 32 participants |
| Region of Enrollment Ireland | 8 participants | 4 participants | 4 participants |
| Region of Enrollment Italy | 11 participants | 9 participants | 2 participants |
| Region of Enrollment Japan | 21 participants | 11 participants | 10 participants |
| Region of Enrollment Netherlands | 6 participants | 1 participants | 5 participants |
| Region of Enrollment New Zealand | 4 participants | 2 participants | 2 participants |
| Region of Enrollment Spain | 15 participants | 8 participants | 7 participants |
| Region of Enrollment Sweden | 7 participants | 5 participants | 2 participants |
| Region of Enrollment Switzerland | 10 participants | 4 participants | 6 participants |
| Region of Enrollment United Kingdom | 40 participants | 17 participants | 23 participants |
| Region of Enrollment United States | 46 participants | 26 participants | 20 participants |
| Sex: Female, Male Female | 144 Participants | 68 Participants | 76 Participants |
| Sex: Female, Male Male | 186 Participants | 98 Participants | 88 Participants |
| Standard of Care Treatment Intravenous (IV) Cyclophosphamide | 102 Participants | 51 Participants | 51 Participants |
| Standard of Care Treatment Oral Cyclophosphamide | 14 Participants | 8 Participants | 6 Participants |
| Standard of Care Treatment Rituximab | 214 Participants | 107 Participants | 107 Participants |
| Type of ANCA-associated vasculitis Granulomatosis with polyangiitis (GPA) | 181 Participants | 91 Participants | 90 Participants |
| Type of ANCA-associated vasculitis Microscopic polyangiitis (MPA) | 149 Participants | 75 Participants | 74 Participants |
| VDI Score | 0.7 units on a scale STANDARD_DEVIATION 1.47 | 0.7 units on a scale STANDARD_DEVIATION 1.54 | 0.7 units on a scale STANDARD_DEVIATION 1.39 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 164 | 2 / 166 |
| other Total, other adverse events | 161 / 164 | 164 / 166 |
| serious Total, serious adverse events | 74 / 164 | 70 / 166 |
Outcome results
Primary
Percentage of Subjects Achieving Disease Remission at Week 26
Disease remission at Week 26 was defined as: * Achieving a BVAS of 0 as determined by the Adjudication Committee; * No administration of glucocorticoids given for ANCA-associated vasculitis within 4 weeks prior to Week 26; * No BVAS \>0 during the 4 weeks prior to Week 26 (if collected for an unscheduled assessment).
Time frame: Week 26
Population: Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone Group | Percentage of Subjects Achieving Disease Remission at Week 26 | 70.1 percentage of participants |
| Avacopan Group | Percentage of Subjects Achieving Disease Remission at Week 26 | 72.3 percentage of participants |
p-value: <0.000195% CI: [-6, 12.8]Summary score test
p-value: =0.238795% CI: [-6, 12.8]Summary score test
Primary
Percentage of Subjects Achieving Sustained Disease Remission at Week 52
Sustained remission at Week 52 was defined as: * Disease remission at Week 26 as defined above; * Disease remission at Week 52 defined as a BVAS of 0 at Week 52 as determined by the Adjudication Committee and no administration of glucocorticoids for treatment of ANCA-associated vasculitis within 4 weeks prior to Week 52; * No disease relapse between Week 26 and Week 52 as determined by the Adjudication Committee.
Time frame: Week 52
Population: Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone Group | Percentage of Subjects Achieving Sustained Disease Remission at Week 52 | 54.9 percentage of participants |
| Avacopan Group | Percentage of Subjects Achieving Sustained Disease Remission at Week 52 | 65.7 percentage of participants |
p-value: <0.000195% CI: [2.6, 22.3]Summary score test
p-value: =0.006695% CI: [2.6, 22.3]Summary score test
Secondary
Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity
WBC=White Blood Cell TEAE=Treatment-Emergent Adverse Event
Time frame: From day 1 throughout the study period (day 421/week 60)
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Infection | 124 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Infection Leading to Death | 2 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Infection Leading to Study Withdrawal | 5 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any TEAE Associated with Hepatic Abnormalities | 19 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Serious Treatment-Emergent Infection | 25 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any TEAE Associated with Low WBC Counts | 39 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Life-threatening Infection | 2 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any TEAE Associated with hypersensitivity | 70 Participants |
| Prednisone Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Severe Treatment-Emergent Infection | 10 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any TEAE Associated with hypersensitivity | 68 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Severe Treatment-Emergent Infection | 12 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Infection | 113 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Serious Treatment-Emergent Infection | 22 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Infection Leading to Study Withdrawal | 4 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Life-threatening Infection | 1 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any Treatment-Emergent Infection Leading to Death | 1 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any TEAE Associated with Hepatic Abnormalities | 22 Participants |
| Avacopan Group | Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity | Any TEAE Associated with Low WBC Counts | 31 Participants |
Secondary
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Lymphocytes (Week 26) | -0.62 10^3 cells/μL | Standard Error 0.09 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Leukocytes (Week 52) | -5.54 10^3 cells/μL | Standard Error 0.365 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Lymphocytes (Week 52) | -0.67 10^3 cells/μL | Standard Error 0.09 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Neutrophils (Week 26) | -5.10 10^3 cells/μL | Standard Error 0.338 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Neutrophils (Week 52) | -4.89 10^3 cells/μL | Standard Error 0.361 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Leukocytes (Week 26) | -5.69 10^3 cells/μL | Standard Error 0.338 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Lymphocytes (Week 52) | -0.82 10^3 cells/μL | Standard Error 0.1 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Lymphocytes (Week 26) | -0.84 10^3 cells/μL | Standard Error 0.099 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Leukocytes (Week 26) | -5.94 10^3 cells/μL | Standard Error 0.387 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Leukocytes (Week 52) | -5.62 10^3 cells/μL | Standard Error 0.395 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Neutrophils (Week 26) | -5.24 10^3 cells/μL | Standard Error 0.38 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) | Neutrophils (Week 52) | -4.95 10^3 cells/μL | Standard Error 0.372 |
Secondary
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Platelets (Week 26) | -73.9 10^9 cells/L | Standard Error 8.49 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Platelets (Week 52) | -75.5 10^9 cells/L | Standard Error 8.01 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Eosinophils (Week 26) | 0.07 10^9 cells/L | Standard Error 0.016 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Eosinophils (Week 52) | 0.05 10^9 cells/L | Standard Error 0.013 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Basophils (Week 26) | -0.01 10^9 cells/L | Standard Error 0.004 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Basophils (Week 52) | -0.01 10^9 cells/L | Standard Error 0.004 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Monocytes (Week 26) | 0.01 10^9 cells/L | Standard Error 0.022 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Monocytes (Week 52) | 0.01 10^9 cells/L | Standard Error 0.024 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Monocytes (Week 52) | -0.01 10^9 cells/L | Standard Error 0.026 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Platelets (Week 26) | -77.1 10^9 cells/L | Standard Error 9.3 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Basophils (Week 26) | -0.00 10^9 cells/L | Standard Error 0.004 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Platelets (Week 52) | -73.8 10^9 cells/L | Standard Error 9.31 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Monocytes (Week 26) | -0.04 10^9 cells/L | Standard Error 0.024 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Eosinophils (Week 26) | 0.07 10^9 cells/L | Standard Error 0.018 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Basophils (Week 52) | -0.01 10^9 cells/L | Standard Error 0.004 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) | Eosinophils (Week 52) | 0.07 10^9 cells/L | Standard Error 0.019 |
Secondary
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5) | Erythrocytes (Week 26) | 0.226 10^12 cells/L | Standard Error 0.045 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5) | Erythrocytes (Week 52) | 0.244 10^12 cells/L | Standard Error 0.041 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5) | Erythrocytes (Week 26) | 0.252 10^12 cells/L | Standard Error 0.0432 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5) | Erythrocytes (Week 52) | 0.279 10^12 cells/L | Standard Error 0.0432 |
Secondary
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5) | Hemoglobin (Week 26) | 1.07 g/dL | Standard Error 0.129 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5) | Hemoglobin (Week 52) | 1.20 g/dL | Standard Error 0.126 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5) | Hemoglobin (Week 26) | 1.10 g/dL | Standard Error 0.12 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5) | Hemoglobin (Week 52) | 1.27 g/dL | Standard Error 0.125 |
Secondary
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5) | Hematocrit (Week 26) | 2.6 percentage of red blood cells | Standard Error 0.38 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5) | Hematocrit (Week 52) | 3.0 percentage of red blood cells | Standard Error 0.37 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5) | Hematocrit (Week 26) | 2.7 percentage of red blood cells | Standard Error 0.38 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5) | Hematocrit (Week 52) | 3.2 percentage of red blood cells | Standard Error 0.38 |
Secondary
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Creatine Kinase (Week 26) | 47.6 U/L | Standard Error 5.27 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Lactate Dehydrogenase (Week 26) | 2.3 U/L | Standard Error 5.68 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Creatine Kinase (Week 52) | 57.6 U/L | Standard Error 5.67 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alkaline Phosphatase (Week 26) | -0.6 U/L | Standard Error 2.47 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alanine Aminotransferase (Week 52) | -8.2 U/L | Standard Error 1.57 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alanine Aminotransferase (Week 26) | -6.8 U/L | Standard Error 1.77 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Aspartate Aminotransferase (Week 26) | 1.9 U/L | Standard Error 0.98 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alkaline Phosphatase (Week 52) | 0.8 U/L | Standard Error 1.77 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Aspartate Aminotransferase (Week 52) | 0.5 U/L | Standard Error 0.85 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Lactate Dehydrogenase (Week 52) | -8.6 U/L | Standard Error 5.33 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Aspartate Aminotransferase (Week 52) | 2.0 U/L | Standard Error 0.69 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Lactate Dehydrogenase (Week 26) | -6.1 U/L | Standard Error 5.4 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Lactate Dehydrogenase (Week 52) | -10.7 U/L | Standard Error 4.8 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alkaline Phosphatase (Week 26) | -3.9 U/L | Standard Error 2.84 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alkaline Phosphatase (Week 52) | -4.0 U/L | Standard Error 2.34 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Creatine Kinase (Week 26) | 76.8 U/L | Standard Error 10.34 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alanine Aminotransferase (Week 26) | -6.1 U/L | Standard Error 1.54 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Alanine Aminotransferase (Week 52) | -7.2 U/L | Standard Error 1.46 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Aspartate Aminotransferase (Week 26) | 2.5 U/L | Standard Error 0.72 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) | Creatine Kinase (Week 52) | 76.3 U/L | Standard Error 9.68 |
Secondary
Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Creatinine (Week 26) | -0.105 mg/dL | Standard Error 0.0569 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Creatinine (Week 52) | -0.200 mg/dL | Standard Error 0.0416 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Urea Nitrogen (Week 26) | -9.4 mg/dL | Standard Error 1.16 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Urea Nitrogen (Week 52) | -7.8 mg/dL | Standard Error 1.11 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Protein (Week 26) | 50 mg/dL | Standard Error 50 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Protein (Week 52) | 160 mg/dL | Standard Error 48 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Cholesterol (Week 26) | 19.0 mg/dL | Standard Error 4.27 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Cholesterol (Week 52) | 13.8 mg/dL | Standard Error 4.28 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | LDL Cholesterol (Week 26) | 22.7 mg/dL | Standard Error 3.66 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | LDL Cholesterol (Week 52) | 21.7 mg/dL | Standard Error 3.48 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Bilirubin (Week 26) | 0.065 mg/dL | Standard Error 0.0182 |
| Prednisone Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Bilirubin (Week 52) | 0.053 mg/dL | Standard Error 0.0185 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Bilirubin (Week 26) | 0.078 mg/dL | Standard Error 0.025 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Creatinine (Week 26) | -0.195 mg/dL | Standard Error 0.0508 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Cholesterol (Week 26) | 7.4 mg/dL | Standard Error 3.99 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Creatinine (Week 52) | -0.244 mg/dL | Standard Error 0.0627 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | LDL Cholesterol (Week 52) | 11.9 mg/dL | Standard Error 3.41 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Urea Nitrogen (Week 26) | -11.0 mg/dL | Standard Error 1.32 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Cholesterol (Week 52) | 9.3 mg/dL | Standard Error 4.05 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Urea Nitrogen (Week 52) | -11.9 mg/dL | Standard Error 1.32 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Bilirubin (Week 52) | 0.057 mg/dL | Standard Error 0.0201 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Protein (Week 26) | 220 mg/dL | Standard Error 47 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | LDL Cholesterol (Week 26) | 12.0 mg/dL | Standard Error 3.47 |
| Avacopan Group | Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) | Protein (Week 52) | 250 mg/dL | Standard Error 41 |
Secondary
Change From Baseline in Vital Signs (1/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline in Vital Signs (1/5) | Diastolic Blood Pressure (Week 26) | 2.7 mmHg | Standard Error 0.98 |
| Prednisone Group | Change From Baseline in Vital Signs (1/5) | Systolic Blood Pressure (Week 52) | -2.4 mmHg | Standard Error 1.64 |
| Prednisone Group | Change From Baseline in Vital Signs (1/5) | Diastolic Blood Pressure (Week 52) | 1.4 mmHg | Standard Error 1.01 |
| Prednisone Group | Change From Baseline in Vital Signs (1/5) | Systolic Blood Pressure (Week 26) | -2.5 mmHg | Standard Error 1.7 |
| Avacopan Group | Change From Baseline in Vital Signs (1/5) | Diastolic Blood Pressure (Week 52) | 1.4 mmHg | Standard Error 1 |
| Avacopan Group | Change From Baseline in Vital Signs (1/5) | Systolic Blood Pressure (Week 52) | -1.0 mmHg | Standard Error 1.6 |
| Avacopan Group | Change From Baseline in Vital Signs (1/5) | Diastolic Blood Pressure (Week 26) | 0.5 mmHg | Standard Error 0.92 |
| Avacopan Group | Change From Baseline in Vital Signs (1/5) | Systolic Blood Pressure (Week 26) | -2.6 mmHg | Standard Error 1.54 |
Secondary
Change From Baseline in Vital Signs (2/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline in Vital Signs (2/5) | Pulse Rate (Week 26) | 2.2 beats/min | Standard Error 1.12 |
| Prednisone Group | Change From Baseline in Vital Signs (2/5) | Pulse Rate (Week 52) | -1.3 beats/min | Standard Error 1.07 |
| Avacopan Group | Change From Baseline in Vital Signs (2/5) | Pulse Rate (Week 26) | 0.9 beats/min | Standard Error 1.25 |
| Avacopan Group | Change From Baseline in Vital Signs (2/5) | Pulse Rate (Week 52) | -0.3 beats/min | Standard Error 1.21 |
Secondary
Change From Baseline in Vital Signs (3/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline in Vital Signs (3/5) | Temperature (Week 26) | -0.03 degree Celsius | Standard Error 0.043 |
| Prednisone Group | Change From Baseline in Vital Signs (3/5) | Temperature (Week 52) | 0.04 degree Celsius | Standard Error 0.044 |
| Avacopan Group | Change From Baseline in Vital Signs (3/5) | Temperature (Week 26) | -0.11 degree Celsius | Standard Error 0.046 |
| Avacopan Group | Change From Baseline in Vital Signs (3/5) | Temperature (Week 52) | -0.11 degree Celsius | Standard Error 0.048 |
Secondary
Change From Baseline in Vital Signs (4/5)
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline in Vital Signs (4/5) | Weight (Week 26) | 3.33 kilogram(s) | Standard Error 0.397 |
| Prednisone Group | Change From Baseline in Vital Signs (4/5) | Weight (Week 52) | 3.27 kilogram(s) | Standard Error 0.477 |
| Avacopan Group | Change From Baseline in Vital Signs (4/5) | Weight (Week 26) | 1.93 kilogram(s) | Standard Error 0.369 |
| Avacopan Group | Change From Baseline in Vital Signs (4/5) | Weight (Week 52) | 2.59 kilogram(s) | Standard Error 0.487 |
Secondary
Change From Baseline in Vital Signs (5/5)
BMI=Body Mass Index
Time frame: Baseline, Week 26 and 52
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline in Vital Signs (5/5) | BMI (Week 26) | 1.13 kilogram(s)/ square meter | Standard Error 0.135 |
| Prednisone Group | Change From Baseline in Vital Signs (5/5) | BMI (Week 52) | 1.12 kilogram(s)/ square meter | Standard Error 0.164 |
| Avacopan Group | Change From Baseline in Vital Signs (5/5) | BMI (Week 26) | 0.67 kilogram(s)/ square meter | Standard Error 0.132 |
| Avacopan Group | Change From Baseline in Vital Signs (5/5) | BMI (Week 52) | 0.94 kilogram(s)/ square meter | Standard Error 0.179 |
Secondary
Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index
SF-36v2: Measure of health- related quality of life (Medical Outcomes Survey Short Form-36 version 2) EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels The SF-36v2 component scores and the EQ-5D-5L VAS score range from 0 (worst health) to 100 (best health). The EQ-5D-5L Index Score ranges from 0 (worst health) to 1 (best health).
Time frame: Baseline, Week 26 and 52
Population: Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug. The number of subjects with data at the specified visit is reported.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L Index Score (Week 52) | -0.0038 Change from baseline | Standard Error 0.01471 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Social Functioning (Week 26) | 11.09 Change from baseline | Standard Error 2.037 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Component Score (Week 26) | 1.344 Change from baseline | Standard Error 0.7432 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Functioning (Week 26) | 1.88 Change from baseline | Standard Error 1.787 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Functioning (Week 52) | 4.82 Change from baseline | Standard Error 1.809 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Physical (Week 26) | 7.52 Change from baseline | Standard Error 2.198 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Physical (Week 52) | 12.27 Change from baseline | Standard Error 2.228 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Bodily Pain (Week 26) | 9.82 Change from baseline | Standard Error 2.197 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Bodily Pain (Week 52) | 11.87 Change from baseline | Standard Error 2.22 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: General Health Perception (Week 26) | -2.89 Change from baseline | Standard Error 1.428 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: General Health Perception (Week 52) | -0.17 Change from baseline | Standard Error 1.442 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Component Score (Week 26) | 3.271 Change from baseline | Standard Error 0.8403 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Component Score (Week 52) | 4.694 Change from baseline | Standard Error 0.8491 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Health (Week 26) | 6.84 Change from baseline | Standard Error 1.331 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Health (Week 52) | 9.66 Change from baseline | Standard Error 1.347 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Emotional (Week 26) | 1.40 Change from baseline | Standard Error 2.183 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Emotional (Week 52) | 4.14 Change from baseline | Standard Error 2.212 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Social Functioning (Week 52) | 13.56 Change from baseline | Standard Error 2.059 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Vitality (Week 26) | 6.42 Change from baseline | Standard Error 1.751 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Vitality (Week 52) | 10.48 Change from baseline | Standard Error 1.77 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L VAS Score (Week 26) | 5.5 Change from baseline | Standard Error 1.39 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L VAS Score (Week 52) | 7.1 Change from baseline | Standard Error 1.41 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L Index Score (Week 26) | -0.0010 Change from baseline | Standard Error 0.01462 |
| Prednisone Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Component Score (Week 52) | 2.626 Change from baseline | Standard Error 0.7505 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Social Functioning (Week 52) | 18.06 Change from baseline | Standard Error 2.03 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Component Score (Week 52) | 4.980 Change from baseline | Standard Error 0.7435 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Component Score (Week 52) | 6.394 Change from baseline | Standard Error 0.8406 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L Index Score (Week 52) | 0.0474 Change from baseline | Standard Error 0.01451 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L VAS Score (Week 26) | 9.1 Change from baseline | Standard Error 1.38 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Component Score (Week 26) | 4.445 Change from baseline | Standard Error 0.7332 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Health (Week 26) | 8.29 Change from baseline | Standard Error 1.318 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Functioning (Week 26) | 7.31 Change from baseline | Standard Error 1.773 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Vitality (Week 26) | 12.03 Change from baseline | Standard Error 1.727 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Physical Functioning (Week 52) | 9.55 Change from baseline | Standard Error 1.79 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Health (Week 52) | 10.89 Change from baseline | Standard Error 1.337 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Physical (Week 26) | 16.78 Change from baseline | Standard Error 2.173 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L Index Score (Week 26) | 0.0229 Change from baseline | Standard Error 0.01438 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Physical (Week 52) | 17.12 Change from baseline | Standard Error 2.198 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Emotional (Week 26) | 7.32 Change from baseline | Standard Error 2.158 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Bodily Pain (Week 26) | 14.75 Change from baseline | Standard Error 2.164 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Vitality (Week 52) | 14.36 Change from baseline | Standard Error 1.75 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Bodily Pain (Week 52) | 16.12 Change from baseline | Standard Error 2.185 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Role Emotional (Week 52) | 9.38 Change from baseline | Standard Error 2.181 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: General Health Perception (Week 26) | 3.12 Change from baseline | Standard Error 1.405 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Social Functioning (Week 26) | 14.50 Change from baseline | Standard Error 2.002 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: General Health Perception (Week 52) | 5.84 Change from baseline | Standard Error 1.42 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | EQ-5D-5L VAS Score (Week 52) | 13.0 Change from baseline | Standard Error 1.39 |
| Avacopan Group | Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index | SF-36v2: Mental Component Score (Week 26) | 4.849 Change from baseline | Standard Error 0.8273 |
Secondary
Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points
VDI=Vasculitis Damage Index; The VDI is comprised of 64 items of damage, grouped into 11 organ-based systems or categorizations. Damage is defined as the presence of non-healing scars and does not give any indication of current disease activity. Damage is also defined as having been present or currently present for at least 3 months. Completion of the form provides a numerical score, which ranges from 0 (best health) to 64 (worst health).
Time frame: Baseline, Week 26 and 52
Population: Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug. The number of subjects with data at baseline and the specified visit is reported.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points | Week 26 | 0.97 score on a scale | Standard Error 0.092 |
| Prednisone Group | Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points | Week 52 | 1.15 score on a scale | Standard Error 0.093 |
| Avacopan Group | Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points | Week 26 | 1.06 score on a scale | Standard Error 0.09 |
| Avacopan Group | Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points | Week 52 | 1.17 score on a scale | Standard Error 0.091 |
Secondary
Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI
GTI-CWS=Glucocorticoid Toxicity Index Cumulative Worsening Score; GTI-AIS=Glucocorticoid Toxicity Index Aggregate Improvement Score; The Glucocorticoid Toxicity Index (GTI) was developed to score glucocorticoid toxicity. The GTI includes: the Cumulative Worsening Score (CWS) that captures cumulative toxicity, both permanent and transient, over the course of time (serves as a cumulative record of toxicity); and the Aggregate Improvement Score that captures both improvement and worsening of toxicity over time (serves as a record of both improving and worsening toxicity). Both scores range from 0 (best health) to 100 (worst health).
Time frame: Baseline, Week 13 and 26
Population: Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug. The number of subjects with data at the specified visit is reported.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-CWS (Week 13) | 36.6 Glucocorticoid Toxicity Index | Standard Error 3.41 |
| Prednisone Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-CWS (Week 26) | 56.6 Glucocorticoid Toxicity Index | Standard Error 3.45 |
| Prednisone Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-AIS (Week 13) | 23.2 Glucocorticoid Toxicity Index | Standard Error 3.46 |
| Prednisone Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-AIS (Week 26) | 23.4 Glucocorticoid Toxicity Index | Standard Error 3.5 |
| Avacopan Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-AIS (Week 26) | 11.2 Glucocorticoid Toxicity Index | Standard Error 3.48 |
| Avacopan Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-CWS (Week 13) | 25.7 Glucocorticoid Toxicity Index | Standard Error 3.4 |
| Avacopan Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-AIS (Week 13) | 9.9 Glucocorticoid Toxicity Index | Standard Error 3.45 |
| Avacopan Group | Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI | GTI-CWS (Week 26) | 39.7 Glucocorticoid Toxicity Index | Standard Error 3.43 |
Secondary
In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks
BVAS=Birmingham Vasculitis Activity Score UACR=Urinary albumin:creatinine ratio
Time frame: Baseline, Week 4, 26 and 52
Population: Intent-to-Treat (ITT) Subjects With Renal Disease (based on BVAS) and Albuminuria (UACR\>=10 mg/g creatinine) at Baseline~ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Prednisone Group | In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks | Week 4 | 0 Percentage change |
| Prednisone Group | In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks | Week 26 | -70 Percentage change |
| Prednisone Group | In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks | Week 52 | -77 Percentage change |
| Avacopan Group | In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks | Week 4 | -40 Percentage change |
| Avacopan Group | In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks | Week 26 | -63 Percentage change |
| Avacopan Group | In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks | Week 52 | -74 Percentage change |
Secondary
In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks
Change from baseline in kidney function, as measured by eGFR (based on the MDRD equation), was measured in subjects with renal disease based on the BVAS renal component. eGFR=estimated glomerular filtration rate BVAS=Birmingham Vasculitis Activity Score MDRD=Modification of Diet in Renal Disease
Time frame: Baseline, Week 26 and 52
Population: Intent-to-Treat (ITT) Subjects With Renal Disease at Baseline (based on BVAS).~ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Prednisone Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks | Week 26 | 2.9 Change in eGFR (mL/min/1.73 m^2) |
| Prednisone Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks | Week 52 | 4.1 Change in eGFR (mL/min/1.73 m^2) |
| Avacopan Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks | Week 26 | 5.8 Change in eGFR (mL/min/1.73 m^2) |
| Avacopan Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks | Week 52 | 7.3 Change in eGFR (mL/min/1.73 m^2) |
Secondary
In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks
BVAS=Birmingham Vasculitis Activity Score MCP-1=monocyte chemoattractant protein-1
Time frame: Baseline, Week 26 and 52
Population: Intent-to-Treat (ITT) Subjects With Renal Disease at Baseline (based on BVAS).~ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Prednisone Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks | Week 26 | -64 Percentage change |
| Prednisone Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks | Week 52 | -71 Percentage change |
| Avacopan Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks | Week 26 | -67 Percentage change |
| Avacopan Group | In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks | Week 52 | -73 Percentage change |
Secondary
Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study
BVAS=Birmingham Vasculitis Activity Score; A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: 1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or 2. having achieved BVAS=0 at any time during the treatment period The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time frame: From day 1 throughout the study period (day 421/week 60)
Population: Intended-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prednisone Group | Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study | 33 Participants |
| Avacopan Group | Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study | 16 Participants |
Secondary
Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator
AE=Adverse Event
Time frame: From day 1 throughout the study period (day 421/week 60)
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prednisone Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of cyclophosphamide IV use to an AE | 30 Participants |
| Prednisone Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of rituximab use to an AE | 61 Participants |
| Prednisone Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of glucocorticoid use to an AE | 131 Participants |
| Prednisone Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of azathioprine use to an AE | 35 Participants |
| Prednisone Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of oral cyclophosphamide use to an AE | 4 Participants |
| Prednisone Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of mycophenolate use to an AE | 9 Participants |
| Prednisone Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of avacopan/placebo to an AE | 103 Participants |
| Avacopan Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of mycophenolate use to an AE | 6 Participants |
| Avacopan Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of avacopan/placebo to an AE | 100 Participants |
| Avacopan Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of glucocorticoid use to an AE | 107 Participants |
| Avacopan Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of cyclophosphamide IV use to an AE | 31 Participants |
| Avacopan Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of oral cyclophosphamide use to an AE | 8 Participants |
| Avacopan Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of rituximab use to an AE | 50 Participants |
| Avacopan Group | Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator | Relationship of azathioprine use to an AE | 28 Participants |
Secondary
Number of Subjects With Clinically Significant ECG Changes From Baseline
Clinical significance was assessed by the individual reading of the ECGs ECG=Electrocardiogram
Time frame: From day 1 throughout the study period (day 421/week 60)
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prednisone Group | Number of Subjects With Clinically Significant ECG Changes From Baseline | 8 Participants |
| Avacopan Group | Number of Subjects With Clinically Significant ECG Changes From Baseline | 12 Participants |
Secondary
Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC
AC=Adjudication Committee; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time frame: Week 4
Population: Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone Group | Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC | 68.9 percentage of participants |
| Avacopan Group | Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC | 62.7 percentage of participants |
Secondary
Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period
The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: 1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or 2. having achieved BVAS=0 at any time during the treatment period The Birmingham Vasculitis Activity Score (BVAS) form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time frame: Week 52
Population: Intent-to-Treat (ITT) Subjects who achieved BVAS=0 during the 52 week treatment period.~ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone Group | Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period | 21.0 percentage of participants |
| Avacopan Group | Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period | 10.1 percentage of participants |
Secondary
Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study
The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: 1. having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or 2. having achieved BVAS=0 at any time during the treatment period ANCA=anti-neutrophil cytoplasmic autoantibody; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time frame: Week 52
Population: Intent-to-Treat (ITT) Subjects in the analysis population for the specified treatment group.~ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone Group | Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study | 12.2 percentage of participants |
| Avacopan Group | Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study | 7.5 percentage of participants |
Secondary
Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs
AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse event
Time frame: From day 1 throughout the study period (day 421/week 60)
Population: Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of TEAEs | 2139 Number |
| Prednisone Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of SAEs | 166 Number |
| Prednisone Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of subjects with SAEs | 74 Number |
| Prednisone Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Subjects with TEAE leading to discontinuation | 28 Number |
| Prednisone Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of subjects with at least one TEAE | 161 Number |
| Avacopan Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Subjects with TEAE leading to discontinuation | 27 Number |
| Avacopan Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of subjects with at least one TEAE | 164 Number |
| Avacopan Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of TEAEs | 1779 Number |
| Avacopan Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of subjects with SAEs | 70 Number |
| Avacopan Group | Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs | Number of SAEs | 116 Number |