ANCA-associated Vasculitis
Conditions
Keywords
ANCA-associated vasculitis, complement, vasculitis, C5aR
Brief summary
The aim of this trial is to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Funding Source - FDA OOPD
Detailed description
Complement 5a and its receptor C5aR (CD88) is involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This is a randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety and efficacy of the C5aR inhibitor CCX168 in subjects with ANCA-associated vasculitis. The aim of this trial is to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
Interventions
DRUGCCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
DRUGCCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids
OTHERPlacebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis or renal limited vasculitis * Male and female subjects, aged at least 18 years, with new or relapsed AAV where treatment with cyclophosphamide or rituximab would be required * Use of adequate contraception during, and for at least the three months after, any administration of study medication is required * Positive indirect immunofluorescence (IIF) test for P-ANCA or C-ANCA, or positive ELISA test for anti-proteinase-3 (PR3) or anti-myeloperoxidase (MPO) at screening * Have at least one major item, or at least 3 other items, or at least 2 renal items on the Birmingham Vasculitis Activity Score (BVAS) version 3 * Estimated glomerular filtration rate (eGFR) ≥ 20 mL per minute
Exclusion criteria
* Severe disease as determined by rapidly progressive glomerulonephritis, alveolar hemorrhage, hemoptysis, rapid-onset mononeuritis multiplex or central nervous system involvement * Any other multi-system autoimmune disease * Medical history of coagulopathy or bleeding disorder * 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 corticosteroids, \>3000 mg methylprednisolone equivalent, within 12 weeks prior to screening * Received an oral daily dose of a corticosteroid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to the screening visit * Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred; received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or plasma exchange within 12 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Baseline to Day 85 | This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms. |
| Proportion of Patients Achieving Disease Response Based on BVAS at Day 85 | Day 85 | Proportion of Patients achieving 50% reduction in the Birmingham Vasculitis Activity Score \[BVAS\] at Day 85 and no worsening in any body system component at day 85 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Day 85 in BVAS. | Baseline to Day 85 | The Birmingham Vasculitis Activity (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). A negative percentage change indicated improvement in health. |
| Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85 | Day 85 | Renal responses among patients (who had hematuria or albuminuria at baseline determined secondary to ANCA-associated vasculitis) were defined as improvement in the following parameters of renal vasculitis: (1) increase from baseline to day 85 in eGFR \[Modification of Diet in Renal Disease (MDRD equation)\], (2) decrease from baseline to day 85 in hematuria (microscopic count of urinary red blood cells \[RBC\]), and (3) decrease from baseline to day 85 in albuminuria (first morning urinary albumin:creatinine ratio). |
| Change in Estimated Glomerular Filtration Rate at Day 85 | Baseline to Day 85 | Mean Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula, for patients with renal disease at baseline. |
| Percentage Change in Estimated Glomerular Filtration Rate at Day 85 | Baseline to Day 85 | Mean Percentage Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula. |
| Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85 | Baseline to Day 85 | Mean Percent Change of Urinary Red Blood Cells (UBC) in Patients in Hematuria at Baseline. |
| Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85. | Day 85 | Proportion of subjects achieving disease remission based on Birmingham Vasculitis Activity Score (BVAS) defined as 0 at Day 85. |
| Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85 | Baseline to Day 85 | Mean Percent Change of Urinary monocyte chemoattractant protein (MCP-1:creatinine) ratio from Baseline |
| Change From Baseline to Day 85 in the VDI | Baseline to Day 85 | The Vasculitis Damage Index (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 to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | Baseline to Day 85 | Change from Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the Short Form-36 (SF-36v2) SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health). |
| Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L | Baseline to Day 85 | Mean Change from baseline to Day 85 in health-related quality-of-life as measured by the Euro Quality-of-Life-5 Domains-5 Levels (EQ-5D-5L). EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given can be converted into an Index Score ranging from 0 for death to 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst imaginable health) to 100 (the best imaginable health). |
| Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85 | Baseline to Day 85 | Proportion of subjects requiring rescue glucocorticoid treatment from Baseline to Day 85 |
| Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85 | Baseline to Day 85 | Mean Percent Change of Urinary Albumin:Creatinine Ratio in Patients with Albuminuria at Baseline |
| Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85. | Day 29 and 85 | Proportion of subjects achieving early disease remission based on Birmingham Vasculitis Activity Score (BVAS) score of 0 at Days 29 and 85. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo BID Plus Standard of Care Capsule, placebo, twice daily plus cyclophosphamide/rituximab plus glucocorticoids | 13 |
| CCX168 10 mg BID Plus Standard of Care Drug: CCX168 10 mg, twice daily plus cyclophosphamide/rituximab plus glucocorticoids | 13 |
| CCX168 30 mg BID Plus Standard of Care Drug: CCX168 30 mg, twice daily plus cyclophosphamide/rituximab plus glucocorticoids | 16 |
| Total | 42 |
Baseline characteristics
| Characteristic | Total | CCX168 10 mg BID Plus Standard of Care | CCX168 30 mg BID Plus Standard of Care | Placebo BID Plus Standard of Care |
|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 13.18 | 60.0 years STANDARD_DEVIATION 10.17 | 55.3 years STANDARD_DEVIATION 13.81 | 58.5 years STANDARD_DEVIATION 15.42 |
| Albumin:creatinine ratio | 104.7 mg/g | 76.1 mg/g | 111.9 mg/g | 135.4 mg/g |
| ANCA-associated vasculitis disease duration at screening (months) | 1.0 months | 1.0 months | 2.5 months | 1.0 months |
| ANCA disease status Newly diagnosed | 27 Participants | 10 Participants | 9 Participants | 8 Participants |
| ANCA disease status Relapsed | 15 Participants | 3 Participants | 7 Participants | 5 Participants |
| ANCA positivity stratification status Anti-MPO positive | 21 Participants | 6 Participants | 8 Participants | 7 Participants |
| ANCA positivity stratification status Anti-PR3 positive | 21 Participants | 7 Participants | 8 Participants | 6 Participants |
| Background treatment Cyclophosphamide | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Background treatment Rituximab | 39 Participants | 13 Participants | 14 Participants | 12 Participants |
| BMI | 30.2 kg/m^2 STANDARD_DEVIATION 9.65 | 27.6 kg/m^2 STANDARD_DEVIATION 8.91 | 31.5 kg/m^2 STANDARD_DEVIATION 7.59 | 31.0 kg/m^2 STANDARD_DEVIATION 12.51 |
| BVAS | 15.3 score on a scale STANDARD_DEVIATION 6.63 | 15.8 score on a scale STANDARD_DEVIATION 8.84 | 15.1 score on a scale STANDARD_DEVIATION 6.43 | 15.0 score on a scale STANDARD_DEVIATION 4.45 |
| Estimated glomerular filtration rate | 59.4 mL/min/1.73 m^2 STANDARD_DEVIATION 27.2 | 56.4 mL/min/1.73 m^2 STANDARD_DEVIATION 26.75 | 61.4 mL/min/1.73 m^2 STANDARD_DEVIATION 31.09 | 60.1 mL/min/1.73 m^2 STANDARD_DEVIATION 24.25 |
| Ethnicity Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Ethnicity Not Hispanic or Latino | 39 Participants | 12 Participants | 14 Participants | 13 Participants |
| Race Black or African American | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race Other | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race White | 38 Participants | 11 Participants | 14 Participants | 13 Participants |
| Sex: Female, Male Female | 23 Participants | 5 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 19 Participants | 8 Participants | 7 Participants | 4 Participants |
| Smoking status Current smoker | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Smoking status Never smoked | 24 Participants | 7 Participants | 10 Participants | 7 Participants |
| Smoking status Past smoker | 16 Participants | 5 Participants | 6 Participants | 5 Participants |
| Type of AAV GPA | 29 Participants | 8 Participants | 12 Participants | 9 Participants |
| Type of AAV Microscopic polyangiitis | 11 Participants | 4 Participants | 4 Participants | 3 Participants |
| Type of AAV Renal-limited vasculitis | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Urinary MCP-1:creatinine ratio | 522.6 pg/mg creatinine | 499.0 pg/mg creatinine | 463.5 pg/mg creatinine | 651.7 pg/mg creatinine |
| Urinary RBCs 30-49 per hpf | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Urinary RBCs 50-75 per hpf | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Urinary RBCs >75 per hpf | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| VDI score | 0.8 score on a scale STANDARD_DEVIATION 1.81 | 0.8 score on a scale STANDARD_DEVIATION 2.49 | 0.6 score on a scale STANDARD_DEVIATION 1.15 | 1.2 score on a scale STANDARD_DEVIATION 1.77 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 16 |
| other Total, other adverse events | 13 / 13 | 12 / 13 | 15 / 16 |
| serious Total, serious adverse events | 3 / 13 | 2 / 13 | 4 / 16 |
Outcome results
Primary
Incidence of Adverse Events
This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.
Time frame: Baseline to Day 85
Population: Safety population: The Safety Population included all subjects who were randomized and received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo BID Plus Standard of Care | Incidence of Adverse Events | 13 Participants |
| CCX168 10 mg BID Plus Standard of Care | Incidence of Adverse Events | 11 Participants |
| CCX168 30 mg BID Plus Standard of Care | Incidence of Adverse Events | 15 Participants |
Primary
Proportion of Patients Achieving Disease Response Based on BVAS at Day 85
Proportion of Patients achieving 50% reduction in the Birmingham Vasculitis Activity Score \[BVAS\] at Day 85 and no worsening in any body system component at day 85
Time frame: Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on-treatment BVAS measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID Plus Standard of Care | Proportion of Patients Achieving Disease Response Based on BVAS at Day 85 | 0.85 proportion of participants |
| CCX168 10 mg BID Plus Standard of Care | Proportion of Patients Achieving Disease Response Based on BVAS at Day 85 | 0.92 proportion of participants |
| CCX168 30 mg BID Plus Standard of Care | Proportion of Patients Achieving Disease Response Based on BVAS at Day 85 | 0.8 proportion of participants |
Secondary
Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2
Change from Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the Short Form-36 (SF-36v2) SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health).
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 postbaseline, on-treatment BVAS measurement.~\*p\<0.05 for CCX168 compared to control for change or percent change from baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Physical functioning | 4.9 score on a scale | Standard Error 7.51 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Role - physical | 4.1 score on a scale | Standard Error 11.44 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Bodily pain | -3.5 score on a scale | Standard Error 8.4 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 General health perceptions | -12.6 score on a scale | Standard Error 4.97 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Vitality | -2.5 score on a scale | Standard Error 8.09 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Social functioning | 4.4 score on a scale | Standard Error 7.81 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Mental health | 8.2 score on a scale | Standard Error 5.49 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Reported health transition | -0.7 score on a scale | Standard Error 0.48 |
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Role - emotional | 8.4 score on a scale | Standard Error 7.76 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Social functioning | 15.2 score on a scale | Standard Error 8.96 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Role - emotional | 10.8 score on a scale | Standard Error 8.42 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Role - physical | 16.1 score on a scale | Standard Error 13.58 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Physical functioning | 13.5 score on a scale | Standard Error 8.33 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Reported health transition | -1.1 score on a scale | Standard Error 0.58 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Bodily pain | 11.0 score on a scale | Standard Error 9.58 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Vitality | 13.8 score on a scale | Standard Error 9.31 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Mental health | 13.3 score on a scale | Standard Error 5.8 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 General health perceptions | -3.8 score on a scale | Standard Error 5.61 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Mental health | 12.6 score on a scale | Standard Error 4.66 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Vitality | 11.8 score on a scale | Standard Error 7.38 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Physical functioning | 17.2 score on a scale | Standard Error 6.61 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Social functioning | 0.5 score on a scale | Standard Error 7.12 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Role - emotional | 12.7 score on a scale | Standard Error 6.8 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 General health perceptions | -6.6 score on a scale | Standard Error 4.49 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Role - physical | 9.6 score on a scale | Standard Error 10.15 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Bodily pain | 14.9 score on a scale | Standard Error 7.85 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the SF-36v2 | SF-36 Reported health transition | -1.6 score on a scale | Standard Error 0.44 |
Secondary
Change From Baseline to Day 85 in the VDI
The Vasculitis Damage Index (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 to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on treatment BVAS measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID Plus Standard of Care | Change From Baseline to Day 85 in the VDI | 0.31 score on a scale | Standard Deviation 0.751 |
| CCX168 10 mg BID Plus Standard of Care | Change From Baseline to Day 85 in the VDI | 0.09 score on a scale | Standard Deviation 0.302 |
| CCX168 30 mg BID Plus Standard of Care | Change From Baseline to Day 85 in the VDI | 0.14 score on a scale | Standard Deviation 0.363 |
Secondary
Change in Estimated Glomerular Filtration Rate at Day 85
Mean Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula, for patients with renal disease at baseline.
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on-treatment BVAS measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID Plus Standard of Care | Change in Estimated Glomerular Filtration Rate at Day 85 | 2.0 ml/min/1.73 m^2 | Standard Deviation 10.71 |
| CCX168 10 mg BID Plus Standard of Care | Change in Estimated Glomerular Filtration Rate at Day 85 | 1.3 ml/min/1.73 m^2 | Standard Deviation 9.75 |
| CCX168 30 mg BID Plus Standard of Care | Change in Estimated Glomerular Filtration Rate at Day 85 | 6.2 ml/min/1.73 m^2 | Standard Deviation 22.17 |
Secondary
Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L
Mean Change from baseline to Day 85 in health-related quality-of-life as measured by the Euro Quality-of-Life-5 Domains-5 Levels (EQ-5D-5L). EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given can be converted into an Index Score ranging from 0 for death to 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst imaginable health) to 100 (the best imaginable health).
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 postbaseline, on-treatment BVAS measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID Plus Standard of Care | Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L | EQ-5D-5L VAS Score | 12.85 score on scale | Standard Deviation 25.413 |
| Placebo BID Plus Standard of Care | Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L | EQ-5D-5L Index Score | 0.03 score on scale | Standard Deviation 0.14 |
| CCX168 10 mg BID Plus Standard of Care | Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L | EQ-5D-5L VAS Score | 20.18 score on scale | Standard Deviation 18.121 |
| CCX168 10 mg BID Plus Standard of Care | Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L | EQ-5D-5L Index Score | 0.05 score on scale | Standard Deviation 0.2 |
| CCX168 30 mg BID Plus Standard of Care | Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L | EQ-5D-5L VAS Score | 11.21 score on scale | Standard Deviation 21.641 |
| CCX168 30 mg BID Plus Standard of Care | Mean Change From Baseline to Day 85 in Health-related Quality-of-life as Measured by the EQ-5D-5L | EQ-5D-5L Index Score | 0.04 score on scale | Standard Deviation 0.138 |
Secondary
Percentage Change in Estimated Glomerular Filtration Rate at Day 85
Mean Percentage Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula.
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on-treatment BVAS measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID Plus Standard of Care | Percentage Change in Estimated Glomerular Filtration Rate at Day 85 | 6.2 % change from baseline (ml/min/1.73 m²) | Standard Deviation 35.65 |
| CCX168 10 mg BID Plus Standard of Care | Percentage Change in Estimated Glomerular Filtration Rate at Day 85 | 0.9 % change from baseline (ml/min/1.73 m²) | Standard Deviation 17.63 |
| CCX168 30 mg BID Plus Standard of Care | Percentage Change in Estimated Glomerular Filtration Rate at Day 85 | 7.7 % change from baseline (ml/min/1.73 m²) | Standard Deviation 27.92 |
Secondary
Percent Change From Baseline to Day 85 in BVAS.
The Birmingham Vasculitis Activity (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). A negative percentage change indicated improvement in health.
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 postbaseline, on-treatment BVAS measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo BID Plus Standard of Care | Percent Change From Baseline to Day 85 in BVAS. | -81.8 percentage change from baseline | Standard Deviation 23.3 |
| CCX168 10 mg BID Plus Standard of Care | Percent Change From Baseline to Day 85 in BVAS. | -95.6 percentage change from baseline | Standard Deviation 8.03 |
| CCX168 30 mg BID Plus Standard of Care | Percent Change From Baseline to Day 85 in BVAS. | -81.7 percentage change from baseline | Standard Deviation 31.28 |
Secondary
Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85
Mean Percent Change of Urinary Albumin:Creatinine Ratio in Patients with Albuminuria at Baseline
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on-treatment BVAS measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo BID Plus Standard of Care | Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85 | -66.281 percentage change from baseline |
| CCX168 10 mg BID Plus Standard of Care | Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85 | -13.890 percentage change from baseline |
| CCX168 30 mg BID Plus Standard of Care | Percent Change of Urinary Albumin:Creatinine Ratio in Patients With Albuminuria From Baseline to Day 85 | -57.596 percentage change from baseline |
Secondary
Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85
Mean Percent Change of Urinary monocyte chemoattractant protein (MCP-1:creatinine) ratio from Baseline
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on-treatment BVAS measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo BID Plus Standard of Care | Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85 | -33.175 percentage change from baseline |
| CCX168 10 mg BID Plus Standard of Care | Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85 | -34.802 percentage change from baseline |
| CCX168 30 mg BID Plus Standard of Care | Percent Change of Urinary MCP-1:Creatinine Ratio From Baseline to Day 85 | 63.567 percentage change from baseline |
Secondary
Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85
Mean Percent Change of Urinary Red Blood Cells (UBC) in Patients in Hematuria at Baseline.
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on-treatment BVAS measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo BID Plus Standard of Care | Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85 | -56.3 percentage change from baseline |
| CCX168 10 mg BID Plus Standard of Care | Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85 | -31.5 percentage change from baseline |
| CCX168 30 mg BID Plus Standard of Care | Percent Change of Urinary Red Blood Cells in Patient With Hematuria From Baseline to Day 85 | -95.0 percentage change from baseline |
Secondary
Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85.
Proportion of subjects achieving disease remission based on Birmingham Vasculitis Activity Score (BVAS) defined as 0 at Day 85.
Time frame: Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 postbaseline, on-treatment BVAS measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID Plus Standard of Care | Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85. | 0.54 proportion of participants |
| CCX168 10 mg BID Plus Standard of Care | Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85. | 0.67 proportion of participants |
| CCX168 30 mg BID Plus Standard of Care | Proportion of Subjects Achieving Disease Remission Based on BVAS at Day 85. | 0.47 proportion of participants |
Secondary
Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85.
Proportion of subjects achieving early disease remission based on Birmingham Vasculitis Activity Score (BVAS) score of 0 at Days 29 and 85.
Time frame: Day 29 and 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 postbaseline, on-treatment BVAS measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID Plus Standard of Care | Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85. | 0.15 proportion of participants |
| CCX168 10 mg BID Plus Standard of Care | Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85. | 0.08 proportion of participants |
| CCX168 30 mg BID Plus Standard of Care | Proportion of Subjects Achieving Early Disease Remission Based on BVAS of 0 at Days 29 and 85. | 0.2 proportion of participants |
Secondary
Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85
Proportion of subjects requiring rescue glucocorticoid treatment from Baseline to Day 85
Time frame: Baseline to Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 postbaseline, on-treatment BVAS measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID Plus Standard of Care | Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85 | 0 proportion of participants |
| CCX168 10 mg BID Plus Standard of Care | Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85 | 0 proportion of participants |
| CCX168 30 mg BID Plus Standard of Care | Proportion of Subjects Requiring Rescue Glucocorticoid Treatment From Baseline to Day 85 | 0 proportion of participants |
Secondary
Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85
Renal responses among patients (who had hematuria or albuminuria at baseline determined secondary to ANCA-associated vasculitis) were defined as improvement in the following parameters of renal vasculitis: (1) increase from baseline to day 85 in eGFR \[Modification of Diet in Renal Disease (MDRD equation)\], (2) decrease from baseline to day 85 in hematuria (microscopic count of urinary red blood cells \[RBC\]), and (3) decrease from baseline to day 85 in albuminuria (first morning urinary albumin:creatinine ratio).
Time frame: Day 85
Population: ITT population: The ITT Population included all subjects who were randomized, received at least 1 dose of study medication, and had at least 1 post-baseline, on-treatment BVAS measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo BID Plus Standard of Care | Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85 | 0.17 proportion of participants |
| CCX168 10 mg BID Plus Standard of Care | Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85 | 0.4 proportion of participants |
| CCX168 30 mg BID Plus Standard of Care | Proportion of Subjects With Hematuria and Albuminuria at Baseline Who Showed a Renal Response at Day 85 | 0.63 proportion of participants |