C3 Glomerulopathy (C3G)
Conditions
Keywords
C3 Glomerulonephritis, C3 glomerulopathy, C3G, DDD, dense deposit disease, membranoproliferative glomerulonephritis, MPGN, C3GN, idiopathic MPGN
Brief summary
The aim of this trial is to evaluate the effect of avacopan treatment on renal disease activity in patients with complement component 3 glomerulopathy (C3G). Funding Source - FDA OOPD
Detailed description
C3 glomerulopathy (C3G) is characterized by evidence of alternative complement activation based on C3 deposition in the glomeruli. There are two forms of the disease: dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). There is no approved treatment for patients with C3G. This is a randomized, double blind, placebo controlled Phase 2 study to evaluate the safety and efficacy of avacopan (CCX168) in patients with C3G. Patients receive avacopan 30mg or matching placebo orally twice-daily. The placebo-controlled treatment period is 26 weeks (182 days). This will be followed by 26 weeks during which time all patients will receive avacopan (results for this second period will be reported in due course in a follow-up publication). Thereafter, all patients will be followed for eight weeks (56 days) without study drug treatment. The primary objective is to evaluate the efficacy of avacopan compared to placebo based on histologic changes in kidney biopsies taken at baseline and after 26 weeks of treatment. The primary endpoint will be based on the percent change from baseline in the C3G Histologic Index for disease activity. Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
Interventions
DRUGAvacopan
Orally administered
DRUGAvacopan Matching Placebo
avacopan matching placebo
Sponsors
Medpace, Inc.
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Matching placebo
Intervention model description
Placebo crossover to active
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Biopsy-proven C3G, either DDD or C3GN, with or without a renal transplant, and with the following observations upon renal biopsy taken within 12 weeks prior to screening or during screening: 1. ≥2-levels of magnitude greater staining of C3 than any combination of IgG, IgM, IgA, kappa and lambda light chains, and C1q by immunohistochemistry, and 2. evidence of proliferative glomerulonephritis (mesangial hypercellularity of greater than 3 mesangial cells per mesangial area and/or endocapillary hypercellularity defined as an increased number of cells within glomerular capillary lumina, causing luminal narrowing) based on light microscopy, and 3. confirmation of the presence of electron dense deposits in the glomeruli on electron microscopy corresponding with the C3 immunofluorescence positivity; 2. Male or female subjects, aged at least 18 years; where approved, adolescents (12-17 year old) may be enrolled; female subjects of childbearing potential (i.e., those who have experienced menarche and who is not permanently sterile or postmenopausal, defined as at least 12 consecutive months with no menses without an alternative medical cause) may participate if adequate contraception is used during, and for at least the three months after study completion; Male subjects with partners of childbearing potential may participate in the study if they had a vasectomy at least 6 months prior to randomization or if adequate contraception is used during, and for at least the 3 months after study completion; Adequate contraception is defined as resulting in a failure rate of less than 1% per year (combined estrogen and progestogen \[oral, intravaginal, or transdermal\], or progestogen-only hormonal contraception (oral, injectable, or implantable), intra-uterine device, intra-uterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, or true sexual abstinence, i.e., in line with the preferred and usual lifestyle of the subject); 3. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; written Assent and Informed Consent must be obtained from the legal guardian in accordance with regional laws or regulations for subjects 12 to 17 years of age; and 4. Judged to be otherwise fit for the study by the Investigator, based on medical history, physical examination, and clinical laboratory assessments. Subjects with clinical laboratory values that are outside of normal limits (other than those specified in the
Exclusion criteria
) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Subjects With Elevated C5b-9 | Week 26 | Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy |
| Percent Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata | Week 26 | Percent change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy \* Multiple Imputation: Missing Week 26 values are imputed using the regression method to create 100 complete datasets. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9 | Week 26 | Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease chronicity over the placebo-controlled treatment period - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. C3G Histological Index for Disease Chronicity Scores can range from 0 to 10. A decrease indicates improvement. C3G=C3 glomerulopathy |
| Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata | Week 26 | Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease chronicity over the placebo-controlled treatment period - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. C3G Histological Index for Disease Chronicity Scores can range from 0 to 10. A decrease indicates improvement. C3G=C3 glomerulopathy |
| Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 | Week 26 | The percent change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. |
| Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata | Week 26 | The percent change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. |
| Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 | Week 26 | The change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. |
| Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata | Week 26 | The change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. |
| Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Subjects With Elevated C5b-9 | Week 26 | Percent change from baseline Over 26 Weeks in UPCR in patients with Abnormal UPCR at Baseline (\>= 0.15 g/g) - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. LSM=Least Squares Mean; UPCR = Urine Protein : Creatinine Ratio |
| Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Combined C5b-9 Strata | Week 26 | Percent change from baseline Over 26 Weeks in UPCR in patients with Abnormal UPCR at Baseline (\>= 0.15 g/g) - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. LSM=Least Squares Mean; UPCR = Urine Protein : Creatinine Ratio |
| Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Subjects With Elevated C5b-9 | Week 26 | Proportion of subjects who have a histologic response defined as a decrease (improvement) in the biopsy-based C3G Histologic Index for activity of at least 35% from baseline to 26 weeks - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy |
| Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Combined C5b-9 Strata | Week 26 | Percent change from baseline over 26 weeks in urinary MCP-1: creatinine ratio - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. LSM=Least Squares Mean; MCP-1=Monocyte Chemoattractant Protein-1 |
| Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9 | Week 26 | Change from baseline over 26 weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. 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). |
| Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata | Week 26 | Change from baseline over 26 weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. 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). |
| Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | Week 26 | Change from baseline over 26 weeks in SF-36 v2 - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. 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). |
| Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | Week 26 | Change from baseline over 26 weeks in SF-36 v2 - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. 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). |
| Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | From day 1 throughout the study period (day 182/week 26) | Number of Subjects with Treatment-emergent SAEs, AEs, relatedness to study medication and Withdrawals Due to AEs AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse events 'Possibly related' refers to the Investigators' causality assessment |
| Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | From day 1 throughout the study period (day 182/week 26) | Number of Treatment-emergent SAEs, AEs, relatedness to study medication and Withdrawals Due to AEs AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse events 'Possibly related' refers to the Investigators' causality assessment |
| Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Subjects With Elevated C5b-9 | Week 26 | Percent change from baseline over 26 weeks in urinary MCP-1: creatinine ratio - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. LSM=Least Squares Mean; MCP-1=Monocyte Chemoattractant Protein-1 |
| Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Combined C5b-9 Strata | Week 26 | Proportion of subjects who have a histologic response defined as a decrease (improvement) in the biopsy-based C3G Histologic Index for activity of at least 35% from baseline to 26 weeks - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy |
Countries
Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group Avacopan-matching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period
Avacopan-matching placebo: Orally administered | 29 |
| Avacopan Group Avacopan (formerly CCX168) 10 mg capsules x 3 administered twice daily during the blinded 26 week blinded treatment period
Avacopan: Orally administered | 28 |
| Total | 57 |
Baseline characteristics
| Characteristic | Total | Placebo Group | Avacopan Group |
|---|---|---|---|
| Age at Diagnosis of C3G | 30.8 years STANDARD_DEVIATION 17.56 | 33.3 years STANDARD_DEVIATION 17.95 | 28.2 years STANDARD_DEVIATION 17.08 |
| Age, Continuous | 34.7 years STANDARD_DEVIATION 16.39 | 37.2 years STANDARD_DEVIATION 17.53 | 32.2 years STANDARD_DEVIATION 15.03 |
| Age, Customized 12-17 years | 2 Participants | 2 Participants | 0 Participants |
| Age, Customized 18-50 years | 43 Participants | 20 Participants | 23 Participants |
| Age, Customized 51-65 years | 8 Participants | 4 Participants | 4 Participants |
| Age, Customized >65 years | 4 Participants | 3 Participants | 1 Participants |
| BMI | 25.34 kilogram(s)/square meter STANDARD_DEVIATION 5.09 | 24.65 kilogram(s)/square meter STANDARD_DEVIATION 3.41 | 26.05 kilogram(s)/square meter STANDARD_DEVIATION 6.375 |
| Body Weight | 75.44 kilogram(s) STANDARD_DEVIATION 16.317 | 72.65 kilogram(s) STANDARD_DEVIATION 12.631 | 78.33 kilogram(s) STANDARD_DEVIATION 19.229 |
| C3GN or DDD C3GN | 48 Participants | 25 Participants | 23 Participants |
| C3GN or DDD DDD | 8 Participants | 4 Participants | 4 Participants |
| C3GN or DDD Missing | 1 Participants | 0 Participants | 1 Participants |
| C5b-9 Stratum <= 244 ng/mL | 14 Participants | 7 Participants | 7 Participants |
| C5b-9 Stratum > 244 ng/mL | 43 Participants | 22 Participants | 21 Participants |
| Duration of C3G | 47.4 months STANDARD_DEVIATION 44.68 | 46.7 months STANDARD_DEVIATION 43.78 | 48.2 months STANDARD_DEVIATION 46.38 |
| eGFR | 75.75 mL/min/1.73m² STANDARD_DEVIATION 41.48 | 72.34 mL/min/1.73m² STANDARD_DEVIATION 43.509 | 79.29 mL/min/1.73m² STANDARD_DEVIATION 39.751 |
| EQ-5D-5L Index Score | 0.88 units on a scale STANDARD_DEVIATION 0.13 | 0.88 units on a scale STANDARD_DEVIATION 0.145 | 0.87 units on a scale STANDARD_DEVIATION 0.116 |
| EQ-5D-5L VAS Score | 76.26 units on a scale STANDARD_DEVIATION 19.862 | 78.83 units on a scale STANDARD_DEVIATION 20.604 | 73.61 units on a scale STANDARD_DEVIATION 19.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 25 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Geographic Region North America | 26 Participants | 12 Participants | 14 Participants |
| Geographic Region Rest of World | 31 Participants | 17 Participants | 14 Participants |
| Height | 172.60 centimeter(s) STANDARD_DEVIATION 9.81 | 171.41 centimeter(s) STANDARD_DEVIATION 8.773 | 173.82 centimeter(s) STANDARD_DEVIATION 10.805 |
| History of Kidney Transplant Missing | 1 Participants | 0 Participants | 1 Participants |
| History of Kidney Transplant No | 53 Participants | 27 Participants | 26 Participants |
| History of Kidney Transplant Yes | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 49 Participants | 25 Participants | 24 Participants |
| Region of Enrollment Belgium | 3 participants | 1 participants | 2 participants |
| Region of Enrollment Canada | 5 participants | 2 participants | 3 participants |
| Region of Enrollment Denmark | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Germany | 3 participants | 2 participants | 1 participants |
| Region of Enrollment Ireland | 6 participants | 3 participants | 3 participants |
| Region of Enrollment Italy | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Netherlands | 6 participants | 5 participants | 1 participants |
| Region of Enrollment Spain | 6 participants | 2 participants | 4 participants |
| Region of Enrollment United Kingdom | 4 participants | 2 participants | 2 participants |
| Region of Enrollment United States | 21 participants | 10 participants | 11 participants |
| Sex: Female, Male Female | 22 Participants | 13 Participants | 9 Participants |
| Sex: Female, Male Male | 35 Participants | 16 Participants | 19 Participants |
| UPCR | 3.44 g/g STANDARD_DEVIATION 2.985 | 2.80 g/g STANDARD_DEVIATION 2.435 | 4.11 g/g STANDARD_DEVIATION 3.38 |
| UPCR (g/g) <= 1 g/g | 14 Participants | 8 Participants | 6 Participants |
| UPCR (g/g) > 1 g/g | 43 Participants | 21 Participants | 22 Participants |
| Urinary MCP-1:Creatinine Ratio | 978.85 pg/mg Creatinine STANDARD_DEVIATION 997.191 | 750.29 pg/mg Creatinine STANDARD_DEVIATION 492.542 | 1215.88 pg/mg Creatinine STANDARD_DEVIATION 1303.359 |
| Viral Test Results - Hepatitis B Virus Surface Antigen Non-reactive | 57 Participants | 29 Participants | 28 Participants |
| Viral Test Results - Hepatitis B Virus Surface Antigen Reactive | 0 Participants | 0 Participants | 0 Participants |
| Viral Test Results - Hepatitis C Virus Antibody Non-reactive | 56 Participants | 29 Participants | 27 Participants |
| Viral Test Results - Hepatitis C Virus Antibody Reactive | 1 Participants | 0 Participants | 1 Participants |
| Viral Test Results HIV-1/2 Antibody Non-reactive | 57 Participants | 29 Participants | 28 Participants |
| Viral Test Results HIV-1/2 Antibody Reactive | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 28 |
| other Total, other adverse events | 24 / 29 | 25 / 28 |
| serious Total, serious adverse events | 3 / 29 | 3 / 28 |
Outcome results
Primary
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Subjects With Elevated C5b-9
Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy
Time frame: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Subjects With Elevated C5b-9 | -0.9 score on a scale |
| Avacopan Group | Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Subjects With Elevated C5b-9 | -1.0 score on a scale |
p-value: 0.96795% CI: [-1.9, 1.8]ANCOVA
Primary
Percent Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata
Percent change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy \* Multiple Imputation: Missing Week 26 values are imputed using the regression method to create 100 complete datasets.
Time frame: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percent Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata | 26.20 Percentage change | Standard Error 47.302 |
| Avacopan Group | Percent Change From Baseline to Week 26 in the C3G Histologic Index for Disease Activity - Combined C5b-9 Strata | -5.77 Percentage change | Standard Error 5.904 |
p-value: 0.3083Van Elteren's Test
Secondary
Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata
Change from baseline over 26 weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. 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: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata | EQ-5D-5L Index Score | 0.0060 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata | EQ-5D-5L VAS Score | 0.1 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata | EQ-5D-5L VAS Score | -1.9 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Combined C5b-9 Strata | EQ-5D-5L Index Score | -0.0138 score on a scale |
Comparison: EQ-5D-5L VAS Scorep-value: 0.489895% CI: [-7.9, 3.8]Mixed Models Analysis
Comparison: EQ-5D-5L Index Scorep-value: 0.482695% CI: [-0.0757, 0.036]Mixed Models Analysis
Secondary
Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9
Change from baseline over 26 weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. 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: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9 | EQ-5D-5L VAS Score | -3.5 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9 | EQ-5D-5L Index Score | 0.0220 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9 | EQ-5D-5L VAS Score | -1.9 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in EQ-5D-5L Health Scale VAS and Index Score - Subjects With Elevated C5b-9 | EQ-5D-5L Index Score | -0.0202 score on a scale |
Comparison: EQ-5D-5L VAS Scorep-value: 0.602595% CI: [-4.6, 7.9]Mixed Models Analysis
Comparison: EQ-5D-5L Index Scorep-value: 0.179795% CI: [-0.1043, 0.0198]Mixed Models Analysis
Secondary
Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata
Change from baseline over 26 weeks in SF-36 v2 - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. 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: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Role-Physical | -2.4712 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Role-Emotional | 4.3024 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Mental Health | 1.503 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: General Health Perceptions | -1.0 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Physical Component | -0.3578 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Bodily Pain | 1.5 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Mental Component | 1.3591 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Vitality | -0.468 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Social Functioning | 4.66 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Physical Functioning | 2.9619 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Role-Emotional | 7.8375 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Physical Functioning | 4.6532 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Role-Physical | 1.2077 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Bodily Pain | -2.0 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: General Health Perceptions | 0.7 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Social Functioning | 1.55 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Mental Health | 3.914 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Physical Component | -0.5096 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Mental Component | 2.3874 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Combined C5b-9 Strata | SF-36v2: Vitality | 4.085 score on a scale |
Comparison: SF-36v2: Physical Component Scorep-value: 0.924295% CI: [-3.3192, 3.0156]Mixed Models Analysis
Comparison: SF-36v2: Mental Component Scorep-value: 0.653495% CI: [-3.4972, 5.5537]Mixed Models Analysis
Secondary
Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9
Change from baseline over 26 weeks in SF-36 v2 - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. 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: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Physical Functioning | 2.8518 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Role-Physical | -4.2592 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Bodily Pain | 3.6 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: General Health Perceptions | -0.9 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Vitality | -2.472 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Role-Emotional | 0.6859 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Mental Health | 2.423 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Physical Component | -0.3257 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Mental Component | 0.7556 score on a scale |
| Placebo Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Social Functioning | 4.58 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Social Functioning | 0.34 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Physical Functioning | 3.2197 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Mental Component | 0.7608 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Role-Physical | 3.5162 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Role-Emotional | 3.2461 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Bodily Pain | -3.5 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Physical Component | 0.0762 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: General Health Perceptions | 1.6 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Mental Health | 2.730 score on a scale |
| Avacopan Group | Change From Baseline Over 26 Weeks in SF-36 v2 - Subjects With Elevated C5b-9 | SF-36v2: Vitality | 3.898 score on a scale |
Comparison: SF-36v2: Physical Component Scorep-value: 0.816195% CI: [-3.0402, 3.844]Mixed Models Analysis
Comparison: SF-36v2: Mental Component Scorep-value: 0.998295% CI: [-4.5994, 4.6099]Mixed Models Analysis
Secondary
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata
Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease chronicity over the placebo-controlled treatment period - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. C3G Histological Index for Disease Chronicity Scores can range from 0 to 10. A decrease indicates improvement. C3G=C3 glomerulopathy
Time frame: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata | 1.6 score on a scale |
| Avacopan Group | Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Combined C5b-9 Strata | 0.8 score on a scale |
p-value: 0.040195% CI: [-1.7, 0]ANCOVA
Secondary
Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9
Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease chronicity over the placebo-controlled treatment period - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. C3G Histological Index for Disease Chronicity Scores can range from 0 to 10. A decrease indicates improvement. C3G=C3 glomerulopathy
Time frame: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9 | 1.5 score on a scale |
| Avacopan Group | Change From Baseline to Week 26 in the C3G Histologic Index for Disease Chronicity - Subjects With Elevated C5b-9 | 1.1 score on a scale |
p-value: 0.336895% CI: [-1.5, 0.5]ANCOVA
Secondary
Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs
Number of Subjects with Treatment-emergent SAEs, AEs, relatedness to study medication and Withdrawals Due to AEs AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse events 'Possibly related' refers to the Investigators' causality assessment
Time frame: From day 1 throughout the study period (day 182/week 26)
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) |
|---|---|---|---|
| Placebo Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with at least one TEAE | 24 participants |
| Placebo Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with SAEs | 3 participants |
| Placebo Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with TEAEs possibly related to Study Medication | 11 participants |
| Placebo Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with TEAEs leading to discontinuation | 1 participants |
| Avacopan Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with TEAEs leading to discontinuation | 1 participants |
| Avacopan Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with at least one TEAE | 25 participants |
| Avacopan Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with TEAEs possibly related to Study Medication | 10 participants |
| Avacopan Group | Number of Subjects With Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of subjects with SAEs | 3 participants |
Secondary
Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs
Number of Treatment-emergent SAEs, AEs, relatedness to study medication and Withdrawals Due to AEs AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse events 'Possibly related' refers to the Investigators' causality assessment
Time frame: From day 1 throughout the study period (day 182/week 26)
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) |
|---|---|---|---|
| Placebo Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of TEAEs | 107 Adverse events |
| Placebo Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of SAEs | 4 Adverse events |
| Placebo Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of TEAEs possibly related to Study Medication | 24 Adverse events |
| Placebo Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of TEAEs leading to discontinuation | 2 Adverse events |
| Avacopan Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of TEAEs leading to discontinuation | 2 Adverse events |
| Avacopan Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of TEAEs | 149 Adverse events |
| Avacopan Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of TEAEs possibly related to Study Medication | 38 Adverse events |
| Avacopan Group | Number of Treatment-emergent SAEs, AEs, Relatedness to Study Medication and Withdrawals Due to AEs | Number of SAEs | 6 Adverse events |
Secondary
Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Combined C5b-9 Strata
Percent change from baseline Over 26 Weeks in UPCR in patients with Abnormal UPCR at Baseline (\>= 0.15 g/g) - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. LSM=Least Squares Mean; UPCR = Urine Protein : Creatinine Ratio
Time frame: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Combined C5b-9 Strata | -14 Percentage change |
| Avacopan Group | Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Combined C5b-9 Strata | -26 Percentage change |
p-value: 0.377895% CI: [0.6, 1.21]Mixed Models Analysis
Secondary
Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Subjects With Elevated C5b-9
Percent change from baseline Over 26 Weeks in UPCR in patients with Abnormal UPCR at Baseline (\>= 0.15 g/g) - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. LSM=Least Squares Mean; UPCR = Urine Protein : Creatinine Ratio
Time frame: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Subjects With Elevated C5b-9 | -14 Percentage change |
| Avacopan Group | Percent Change From Baseline Over 26 Weeks in UPCR in Patients With Abnormal UPCR at Baseline - Subjects With Elevated C5b-9 | -16 Percentage change |
p-value: 0.928495% CI: [0.67, 1.45]Mixed Models Analysis
Secondary
Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Combined C5b-9 Strata
Percent change from baseline over 26 weeks in urinary MCP-1: creatinine ratio - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. LSM=Least Squares Mean; MCP-1=Monocyte Chemoattractant Protein-1
Time frame: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Combined C5b-9 Strata | 1 Percentage change |
| Avacopan Group | Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Combined C5b-9 Strata | -12 Percentage change |
p-value: 0.323395% CI: [0.66, 1.15]Mixed Models Analysis
Secondary
Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Subjects With Elevated C5b-9
Percent change from baseline over 26 weeks in urinary MCP-1: creatinine ratio - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. LSM=Least Squares Mean; MCP-1=Monocyte Chemoattractant Protein-1
Time frame: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Subjects With Elevated C5b-9 | 1 Percentage change |
| Avacopan Group | Percent Change From Baseline Over 26 Weeks in Urinary MCP-1 - Subjects With Elevated C5b-9 | -23 Percentage change |
p-value: 0.08195% CI: [0.55, 1.04]Mixed Models Analysis
Secondary
Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Combined C5b-9 Strata
Proportion of subjects who have a histologic response defined as a decrease (improvement) in the biopsy-based C3G Histologic Index for activity of at least 35% from baseline to 26 weeks - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy
Time frame: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with C3G Histological Index of Disease Activity Percent Change at Week 26 is reported.~The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Combined C5b-9 Strata | Responder | 7 Participants |
| Placebo Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Combined C5b-9 Strata | Non-Responder | 18 Participants |
| Avacopan Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Combined C5b-9 Strata | Responder | 4 Participants |
| Avacopan Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Combined C5b-9 Strata | Non-Responder | 21 Participants |
p-value: 0.3106Cochran-Mantel-Haenszel
Secondary
Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Subjects With Elevated C5b-9
Proportion of subjects who have a histologic response defined as a decrease (improvement) in the biopsy-based C3G Histologic Index for activity of at least 35% from baseline to 26 weeks - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy
Time frame: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with C3G Histological Index of Disease Activity Percent Change at Week 26 is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Subjects With Elevated C5b-9 | Responder | 4 Participants |
| Placebo Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Subjects With Elevated C5b-9 | Non-Responder | 16 Participants |
| Avacopan Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Subjects With Elevated C5b-9 | Responder | 2 Participants |
| Avacopan Group | Proportion of Subjects Who Have a Histologic Response Defined as a Decrease (Improvement) in the Biopsy-based C3G Histologic Index for Activity of at Least 35% From Baseline to 26 Weeks - Subjects With Elevated C5b-9 | Non-Responder | 16 Participants |
p-value: 0.4591Cochran-Mantel-Haenszel
Secondary
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata
The change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population.
Time frame: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata | -3.35 mL/min/1.73m^2 |
| Avacopan Group | Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata | 0.47 mL/min/1.73m^2 |
p-value: 0.206995% CI: [-2.14, 9.77]Mixed Models Analysis
Secondary
Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9
The change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population.
Time frame: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 | -3.57 mL/min/1.73m^2 |
| Avacopan Group | Renal Function as Assessed by Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 | 0.44 mL/min/1.73m^2 |
p-value: 0.263895% CI: [-3.08, 11.08]Mixed Models Analysis
Secondary
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata
The percent change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population.
Time frame: Week 26
Population: Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata | -5.88 Percentage change |
| Avacopan Group | Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Combined C5b-9 Strata | 4.79 Percentage change |
p-value: 0.022195% CI: [1.56, 19.78]Mixed Models Analysis
Secondary
Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9
The percent change from baseline over 26 weeks in estimated Glomerular Filtration Rate (eGFR) - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population.
Time frame: Week 26
Population: Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat (ITT) Population. The number of subjects with data at baseline and the specified visit is reported.~ITT Population: The ITT Population included all randomized subjects who received at least one dose of study medication; subjects with a histologic activity score of 0 at baseline or who were ongoing and had not completed the Week 26 visit were not included in the ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Group | Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 | -4.73 Percentage change |
| Avacopan Group | Renal Function as Assessed by Percent Change From Baseline Over 26 Weeks in eGFR - Subjects With Elevated C5b-9 | 6.11 Percentage change |
p-value: 0.053495% CI: [-0.16, 21.85]Mixed Models Analysis