Focal Segmental Glomerulosclerosis, FSGS, Glomerulosclerosis
Conditions
Brief summary
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects with FSGS to be conducted in the North America, Europe and Australia
Detailed description
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects with Focal Segmental Glomerulosclerosis (FSGS) to be conducted in the North America, Europe and Australia. The aim of this study is to evaluate the effect of treatment with CCX140-B, a selective antagonist of C-C chemokine receptor type 2 in subjects with focal segmental glomerulosclerosis on urinary protein excretion as assessed by changes in urine protein to creatinine ratio (UPCR). Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.
Interventions
OTHERPlacebo
Three placebo tablets, taken twice daily (BID), per os, for 84 days (12 weeks)
DRUGCCX140-B
One 5 mg CCX140-B tablet and 2 placebo tablets in the morning; 3 placebo tablets in the evening; per os, for 84 days.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind
Intervention model description
Randomized, placebo-controlled, Phase 2
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects aged 18-75 2. UPCR ≥ 1 g protein/g creatinine (or at 113 mg.mmol) at screening 3. Diagnosis of FSGS based on renal biopsy or high risk genetic variant 4. Diagnosis of one of primary FSGS based on characteristic histopathology, medical history and clinical course or FSGS secondary to genetic variants associated with increased risk or severity. 5. Estimated glomerular filtration rate (eGFR) \>30 mL/min/1.73m2 6. Clinical stable blood pressure not to exceed 145/95 mmHg 7. RAAS blockers must be stable for at least 4 weeks prior to screening and projected to remain stable through week 12, unless adjustments are required for management of hypertension. 8. Immunosuppressive or immunomodulatory therapy must be stable for at least 4 weeks prior to screening and projected to remain stable through study week 12 9. Glucocorticoids must be stable for at least 4 weeks prior to screening and projected to remain stable through study week 12. 10. Both genders of childbearing potential must agree to use adequate contraception during and for at least 3 months after the last dose of study drug. 11. Subjects must be willing and able to give written Informed Consent and to comply with protocol requirements. 12. Subjects must be judged to be otherwise fit for the study by the Investigator. -
Exclusion criteria
1. Pregnant or nursing 2. History of organ transplantation 3. On an organ transplant waiting list or anticipated organ transplant within 6 months of screening 4. Anti-CD20 monoclonal antibodies within 20 months of screening are exclusionary. Subjects that used anti CD20 monoclonal antibodies prior to week 20 are allowed with confirmed recovery of CD20+ B cell population to within normal range 5. Plasmapheresis within 12 weeks of screening 6. BMI ≥40 7. Participation in any clinical study of an investigational product within 12 weeks or 5 half-lives of screening 8. Currently on dialysis or likely to require dialysis during the blinded treatment phase of the study. 9. History or presence of any form of cancer within 5 years of screening except excised basal cell or squamous cell carcinoma or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or completed resected without evidence or recurrence. 10. Positive HBV, HCV, or HIV viral screening test. Subjects who have received highly effective therapy for HCV demonstrated to have negative viral titers for at least 6 months following discontinuation of treatment, will be considered to have a negative HCV screening test 11. Renal disease associated with disorders other than FSGS that is active or has significant risk of progressing during the course of the study. 12. Disorders that are associated with FSGS lesions. 13. Evidence of tuberculosis. 14. Evidence of hepatic disease with the exception that isolated INR elevation in the absence of other significant liver enzyme abnormalities is explained by anticoagulant therapy, (e.g. warfarin) 15. Hematologic abnormalities as follows: Hb \<8 g/dL, platelets \<50,000, ANC \<1000 cells/µL) at baseline. 16. QTcF greater than 450 msec. 17. History of alcohol or illicit drug abuse or of lithium, pamidronate and interferon. Recreational use of cannabis is not excluded where legal. 18. History of gastrointestinal conditions that may interfere with study medication compliance. 19. Known hypersensitivity to CCX140-B or inactive ingredients of the CCX140-B tablets (including microcrystalline cellulose, starch, crospovidone, magnesium stearate, or silicon dioxide). 20. History or presence of systemic disorder other than FSGS that requires, or is expected to require, systemic glucocorticoids or immune modulators during the study; topical or inhaled glucocorticoids and immune modulators are not excluded. 21. History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation. 22. Subjects taking strong CYP3A4 inducers or strong CYP3A4 inhibitors within two weeks prior to screening. 23. Subjects taking lithium or interferon; subjects taking non-steroidal anti-inflammatory agents (NSAIDS) chronically (intermittent, i.e. occasional NSAIDS for pain or fever is discouraged, but is not excluded). \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Urine Protein | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Urine Albumin | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Urine Creatinine | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Eosinophils | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in UPCR at Week 12 | Baseline to Week 12 | Least squared mean ratio of UPCR (Urine protein g:creatinine g) compared to baseline at Week 12 in the ITT population. ITT- Intent to treat |
| Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | Baseline to Week 12, and Week 12 to Week 24 | TEAEs leading to study withdrawal means study drug discontinuation in this endpoint. |
| Change From Baseline in Activated Partial Thromboplastin Time | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal Range: 23.9 - 40.0 |
| Change From Baseline in Plasma Alanine Aminotransferase | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal Range: 6 - 41 U/L |
| Change From Baseline in Plasma Alkaline Phosphatase | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Amylase | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 22-123 U/L |
| Change From Baseline in Plasma Aspartate Aminotransferase | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range : 9-34 U/L |
| Change From Baseline in Plasma Bicarbonate | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 21-33 mmol/L |
| Change From Baseline in Plasma Bilirubin | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 0.1-1.10 mg/dL |
| Change From Baseline in Plasma C Reactive Protein | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 0.0-3.0 mg/L |
| Change From Baseline in Plasma Calcium | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 8.5-10.5 mg/dL |
| Change From Baseline in Plasma Chloride | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 95-110 mmol/L |
| Change From Baseline in Plasma Cholesterol | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 100-200 mg/dL |
| Change From Baseline in Plasma Creatine Kinase | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 23-210 U/L |
| Change From Baseline in Eosinophils/Leukocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Creatinine | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 0.62-1.44 mg/dL |
| Change From Baseline in Plasma Cystatin C | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Normal range: 0.53-0.95 mg/L |
| Change From Baseline in Plasma Direct Bilirubin | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Glucose | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | HGB - Hemoglobin |
| Change From Baseline in Plasma HDL Cholesterol | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | HDL -High-density lipoprotein |
| Change From Baseline in Plasma Indirect Bilirubin | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma LDL Cholesterol | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | LDL - Low-density lipoprotein |
| Change From Baseline in Lactate Dehydrogenase | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Pancreatic Lipase | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Magnesium | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Phosphate | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Potassium | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Protein | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Prothrombin Intl. Normalised Ratio | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Prothrombin Time | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Sodium | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Triglycerides | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Urate | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Plasma Urea Nitrogen | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Basophils | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Basophils/Leukocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Erythrocyte Mean Corpuscular Volume | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Erythrocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Hematocrit | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Hemoglobin | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Leukocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Lymphocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Lymphocytes/Leukocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Monocytes/Leukocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Neutrophils | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Neutrophils/Leukocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Platelets | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
| Change From Baseline in Reticulocytes/Erythrocytes | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Endpoint at Week 12 for Double-Blind Treatment Period and Endpoint at Week 24 for Open-Label Extension | 1\. Proportion of subjects achieving complete renal remission by the following definition at Weeks 12 and 24 o Reduction in UPCR to \<0.3 g/g o Serum albumin within normal range (for subjects with abnormal serum creatinine levels at baseline, return to normal levels for that age group; for subjects with normal serum creatinine levels at baseline, final value within 20% of baseline levels) 2. Proportion of subjects achieving partial remission defined as UPCR reduction of ≥50% from baseline and UPCR \<3.5 g/g (definition 1), assessed at Weeks 12 and 24 3. Proportion of subjects achieving partial remission defined Decrease in UPCR to less than 1.5 g/g and at least a 40% reduction in proteinuria from baseline (definition 2), assessed at Weeks 12 and 24 |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension) | Change from baseline in eGFR calculated by the CKD-EPI Cystatin C equation, CKD-EPI Creatinine equation, CKD-EPI Creatinine-Cystatin C equation and MDRD Creatinine equation at Weeks 12 and 24. CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; MDRD: Modification of Diet in Renal Disease Open label extension covers Baseline to Week 12 and Baseline to Week 24 |
Countries
Australia, Canada, France, Italy, New Zealand, Poland, United Kingdom, United States
Participant flow
Recruitment details
The recruitment took place in Australia, Canada, France, Italy, New Zealand, Poland, United Kingdom, and in the United States. The target was to enroll 40 male or female subjects. The first patient was enrolled on 17 May 2018. A total of 84 subjects were screened; 38 subjects failed screening and 46 subjects were randomized.
Pre-assignment details
Eighty-four (84) patients were screened. Screen failure occurred in 38 (45.2%) subjects due to not meeting inclusion or exclusion criteria (35 \[41.7%\] subjects) and other reasons (3 \[3.6%\] subjects).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo control | 12 |
| CCX140-B 5 mg Once Daily CCX140-B 5 mg once daily
CCX140-B: CCX140-B is an orally administered selective antagonist of CCR2 | 11 |
| CCX140-B 10 mg Twice Daily CCX140-B 10 mg twice daily
CCX140-B: CCX140-B is an orally administered selective antagonist of CCR2 | 12 |
| CCX140-B 15 mg Twice Daily CCX140-B 15 mg twice daily
CCX140-B: CCX140-B is an orally administered selective antagonist of CCR2 | 11 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double Blind Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
| Open Label Extension | Other | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | CCX140-B 5 mg Once Daily | Total | CCX140-B 15 mg Twice Daily | CCX140-B 10 mg Twice Daily |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 44 Participants | 10 Participants | 11 Participants |
| Age, Continuous | 46.3 years STANDARD_DEVIATION 12.5 | 41.7 years STANDARD_DEVIATION 12.7 | 42.3 years STANDARD_DEVIATION 13.47 | 43.4 years STANDARD_DEVIATION 13.26 | 37.9 years STANDARD_DEVIATION 15.51 |
| Baseline eGFR (CKD-EPI Creatinine-Cystatin C) | 72.75 ml/min/1.73 m^2 STANDARD_DEVIATION 36.204 | 56.18 ml/min/1.73 m^2 STANDARD_DEVIATION 28.927 | 61.35 ml/min/1.73 m^2 STANDARD_DEVIATION 29.163 | 61.36 ml/min/1.73 m^2 STANDARD_DEVIATION 32.265 | 54.67 ml/min/1.73 m^2 STANDARD_DEVIATION 15.622 |
| Baseline urine MCP-1 creatinine ratio | 453.74 g protein/g creatinine STANDARD_DEVIATION 438.384 | 576.41 g protein/g creatinine STANDARD_DEVIATION 470.089 | 490.67 g protein/g creatinine STANDARD_DEVIATION 399.559 | 430.66 g protein/g creatinine STANDARD_DEVIATION 325.651 | 504.02 g protein/g creatinine STANDARD_DEVIATION 388.569 |
| Concomitant use of ACE inhibitor or ARB or aldosterone antagonists No | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Concomitant use of ACE inhibitor or ARB or aldosterone antagonists Yes | 12 Participants | 10 Participants | 43 Participants | 10 Participants | 11 Participants |
| Concomitant use of all calcineurin inhibitors combined No | 10 Participants | 7 Participants | 34 Participants | 8 Participants | 9 Participants |
| Concomitant use of all calcineurin inhibitors combined Yes | 2 Participants | 4 Participants | 12 Participants | 3 Participants | 3 Participants |
| Concomitant use of calcineurin inhibitors cyclosporin No | 11 Participants | 10 Participants | 40 Participants | 10 Participants | 9 Participants |
| Concomitant use of calcineurin inhibitors cyclosporin Yes | 1 Participants | 1 Participants | 6 Participants | 1 Participants | 3 Participants |
| Concomitant use of glucocorticoids No | 6 Participants | 7 Participants | 27 Participants | 6 Participants | 8 Participants |
| Concomitant use of glucocorticoids Yes | 6 Participants | 4 Participants | 19 Participants | 5 Participants | 4 Participants |
| Current use of glucocorticoids and/or immunosuppressive medications No | 5 Participants | 5 Participants | 21 Participants | 5 Participants | 6 Participants |
| Current use of glucocorticoids and/or immunosuppressive medications Yes | 7 Participants | 6 Participants | 25 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 10 Participants | 41 Participants | 9 Participants | 11 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 16 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 30 Participants | 8 Participants | 7 Participants |
| UPCR | 2.19 g protein/g creatinine STANDARD_DEVIATION 1.029 | 2.00 g protein/g creatinine STANDARD_DEVIATION 1.149 | 2.54 g protein/g creatinine STANDARD_DEVIATION 1.773 | 3.12 g protein/g creatinine STANDARD_DEVIATION 2.504 | 2.86 g protein/g creatinine STANDARD_DEVIATION 2.008 |
| UPCR at baseline UPCR < 3.5 at baseline | 11 g/dL | 10 g/dL | 37 g/dL | 7 g/dL | 9 g/dL |
| UPCR at baseline UPCR ≥ 3.5 at baseline | 1 g/dL | 1 g/dL | 9 g/dL | 4 g/dL | 3 g/dL |
| UPCR at screening UPCR < 3.5 at screening | 9 Participants | 9 Participants | 35 Participants | 8 Participants | 9 Participants |
| UPCR at screening UPCR ≥ 3.5 at screening | 3 Participants | 2 Participants | 11 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 7 / 11 | 8 / 11 | 10 / 12 | 8 / 11 | 7 / 11 | 6 / 11 | 6 / 11 | 5 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 11 | 1 / 11 | 0 / 10 |
Outcome results
Primary
Change From Baseline in Activated Partial Thromboplastin Time
Normal Range: 23.9 - 40.0
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Population: Data is not available for all participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Activated Partial Thromboplastin Time | Week 12 | 2.40 second | Standard Deviation 4.259 |
| Placebo | Change From Baseline in Activated Partial Thromboplastin Time | Week 24 | 2.91 second | Standard Deviation 4.132 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Activated Partial Thromboplastin Time | Week 12 | 2.05 second | Standard Deviation 4.396 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Activated Partial Thromboplastin Time | Week 24 | 1.39 second | Standard Deviation 3.187 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Activated Partial Thromboplastin Time | Week 12 | 2.36 second | Standard Deviation 2.614 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Activated Partial Thromboplastin Time | Week 24 | 2.34 second | Standard Deviation 6.169 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Activated Partial Thromboplastin Time | Week 24 | 0.10 second | Standard Deviation 3.223 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Activated Partial Thromboplastin Time | Week 12 | 1.28 second | Standard Deviation 2.508 |
| Open-label Extension | Change From Baseline in Activated Partial Thromboplastin Time | Week 12 | 1.76 second | Standard Deviation 4.332 |
| Open-label Extension | Change From Baseline in Activated Partial Thromboplastin Time | Week 24 | 1.76 second | Standard Deviation 4.332 |
Primary
Change From Baseline in Basophils
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Basophils | 0.02 cells x 10^9/L | Standard Deviation 0.058 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Basophils | 0.03 cells x 10^9/L | Standard Deviation 0.047 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Basophils | 0.02 cells x 10^9/L | Standard Deviation 0.6 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Basophils | -0.03 cells x 10^9/L | Standard Deviation 0.048 |
| Open-label Extension | Change From Baseline in Basophils | 0.02 cells x 10^9/L | Standard Deviation 0.063 |
Primary
Change From Baseline in Basophils/Leukocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Basophils/Leukocytes | 0.08 percentage of basophils in leukocytes | Standard Deviation 0.389 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Basophils/Leukocytes | -0.01 percentage of basophils in leukocytes | Standard Deviation 0.459 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Basophils/Leukocytes | 0.18 percentage of basophils in leukocytes | Standard Deviation 0.547 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Basophils/Leukocytes | -0.13 percentage of basophils in leukocytes | Standard Deviation 0.419 |
| Open-label Extension | Change From Baseline in Basophils/Leukocytes | 0.16 percentage of basophils in leukocytes | Standard Deviation 0.433 |
Primary
Change From Baseline in Eosinophils
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Eosinophils | 0.01 cells x 10^9/L | Standard Deviation 0.108 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Eosinophils | 0.01 cells x 10^9/L | Standard Deviation 0.122 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Eosinophils | 0.00 cells x 10^9/L | Standard Deviation 0.184 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Eosinophils | 0.01 cells x 10^9/L | Standard Deviation 0.099 |
| Open-label Extension | Change From Baseline in Eosinophils | 0.03 cells x 10^9/L | Standard Deviation 0.162 |
Primary
Change From Baseline in Eosinophils/Leukocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Eosinophils/Leukocytes | 0.32 percentage of Eosinophils in Leukocytes | Standard Deviation 1.375 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Eosinophils/Leukocytes | 0.09 percentage of Eosinophils in Leukocytes | Standard Deviation 0.984 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Eosinophils/Leukocytes | -0.02 percentage of Eosinophils in Leukocytes | Standard Deviation 2.245 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Eosinophils/Leukocytes | 0.33 percentage of Eosinophils in Leukocytes | Standard Deviation 1.43 |
| Open-label Extension | Change From Baseline in Eosinophils/Leukocytes | 0.27 percentage of Eosinophils in Leukocytes | Standard Deviation 1.922 |
Primary
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | -0.2 picogram(s) | Standard Deviation 0.58 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | -0.3 picogram(s) | Standard Deviation 0.47 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | -0.5 picogram(s) | Standard Deviation 0.82 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | 0.0 picogram(s) | Standard Deviation 0.82 |
| Open-label Extension | Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin | -0.1 picogram(s) | Standard Deviation 0.8 |
Primary
Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration
HGB - Hemoglobin
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration | -0.20 g/dL | Standard Deviation 0.603 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration | -0.18 g/dL | Standard Deviation 0.778 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration | -0.24 g/dL | Standard Deviation 0.439 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration | -0.16 g/dL | Standard Deviation 0.556 |
| Open-label Extension | Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration | -0.28 g/dL | Standard Deviation 0.891 |
Primary
Change From Baseline in Erythrocyte Mean Corpuscular Volume
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Erythrocyte Mean Corpuscular Volume | -0.21 fL | Standard Deviation 1.472 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Erythrocyte Mean Corpuscular Volume | -0.02 fL | Standard Deviation 2.093 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Erythrocyte Mean Corpuscular Volume | -0.33 fL | Standard Deviation 1.251 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Erythrocyte Mean Corpuscular Volume | 0.03 fL | Standard Deviation 1.931 |
| Open-label Extension | Change From Baseline in Erythrocyte Mean Corpuscular Volume | 0.44 fL | Standard Deviation 1.801 |
Primary
Change From Baseline in Erythrocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Erythrocytes | -0.004 cells x 10^12/L | Standard Deviation 0.2946 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Erythrocytes | 0.055 cells x 10^12/L | Standard Deviation 0.2211 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Erythrocytes | 0.010 cells x 10^12/L | Standard Deviation 0.2326 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Erythrocytes | -0.55 cells x 10^12/L | Standard Deviation 0.1761 |
| Open-label Extension | Change From Baseline in Erythrocytes | -0.003 cells x 10^12/L | Standard Deviation 0.2968 |
Primary
Change From Baseline in Hematocrit
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematocrit | -0.3 percentage of red blood cells in blood | Standard Deviation 2.34 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Hematocrit | 0.5 percentage of red blood cells in blood | Standard Deviation 2.11 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Hematocrit | -0.1 percentage of red blood cells in blood | Standard Deviation 2.26 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Hematocrit | -0.8 percentage of red blood cells in blood | Standard Deviation 1.55 |
| Open-label Extension | Change From Baseline in Hematocrit | 0.2 percentage of red blood cells in blood | Standard Deviation 2.61 |
Primary
Change From Baseline in Hemoglobin
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin | -0.12 g/dL | Standard Deviation 0.802 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Hemoglobin | 0.13 g/dL | Standard Deviation 0.588 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Hemoglobin | -0.10 g/dL | Standard Deviation 0.784 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Hemoglobin | -0.25 g/dL | Standard Deviation 0.488 |
| Open-label Extension | Change From Baseline in Hemoglobin | -0.07 g/dL | Standard Deviation 0.923 |
Primary
Change From Baseline in Lactate Dehydrogenase
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Lactate Dehydrogenase | -10.2 U/L | Standard Deviation 25.67 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Lactate Dehydrogenase | -26.4 U/L | Standard Deviation 69.73 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Lactate Dehydrogenase | -14.5 U/L | Standard Deviation 26.09 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Lactate Dehydrogenase | 5.1 U/L | Standard Deviation 27.15 |
| Open-label Extension | Change From Baseline in Lactate Dehydrogenase | -12.0 U/L | Standard Deviation 41.83 |
Primary
Change From Baseline in Leukocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Leukocytes | -0.98 cells x 10^3/microlitre | Standard Deviation 1.915 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Leukocytes | 0.45 cells x 10^3/microlitre | Standard Deviation 1.012 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Leukocytes | 0.37 cells x 10^3/microlitre | Standard Deviation 1.819 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Leukocytes | -0.09 cells x 10^3/microlitre | Standard Deviation 1.928 |
| Open-label Extension | Change From Baseline in Leukocytes | -0.09 cells x 10^3/microlitre | Standard Deviation 1.711 |
Primary
Change From Baseline in Lymphocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Lymphocytes | -0.080 cells x 10^3/L | Standard Deviation 0.2152 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Lymphocytes | 0.122 cells x 10^3/L | Standard Deviation 0.3541 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Lymphocytes | 0.099 cells x 10^3/L | Standard Deviation 0.4865 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Lymphocytes | 0.194 cells x 10^3/L | Standard Deviation 0.9257 |
| Open-label Extension | Change From Baseline in Lymphocytes | 0.161 cells x 10^3/L | Standard Deviation 0.4165 |
Primary
Change From Baseline in Lymphocytes/Leukocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Lymphocytes/Leukocytes | 2.51 percentage of lymphocytes in leukocytes | Standard Deviation 5.052 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Lymphocytes/Leukocytes | 0.06 percentage of lymphocytes in leukocytes | Standard Deviation 6.287 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Lymphocytes/Leukocytes | -0.99 percentage of lymphocytes in leukocytes | Standard Deviation 8.132 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Lymphocytes/Leukocytes | 1.52 percentage of lymphocytes in leukocytes | Standard Deviation 7.013 |
| Open-label Extension | Change From Baseline in Lymphocytes/Leukocytes | 2.61 percentage of lymphocytes in leukocytes | Standard Deviation 7.099 |
Primary
Change From Baseline in Monocytes/Leukocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Monocytes/Leukocytes | 1.38 percentage of monocytes in leukocytes | Standard Deviation 1.641 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Monocytes/Leukocytes | 0.25 percentage of monocytes in leukocytes | Standard Deviation 2.056 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Monocytes/Leukocytes | 0.99 percentage of monocytes in leukocytes | Standard Deviation 3.022 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Monocytes/Leukocytes | 0.56 percentage of monocytes in leukocytes | Standard Deviation 1.532 |
| Open-label Extension | Change From Baseline in Monocytes/Leukocytes | -0.21 percentage of monocytes in leukocytes | Standard Deviation 2.262 |
Primary
Change From Baseline in Neutrophils
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Neutrophils | -0.954 cells x 10^3/L | Standard Deviation 1.629 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Neutrophils | 0.255 cells x 10^3/L | Standard Deviation 1.1041 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Neutrophils | 0.137 cells x 10^3/L | Standard Deviation 1.6023 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Neutrophils | -0.289 cells x 10^3/L | Standard Deviation 1.4171 |
| Open-label Extension | Change From Baseline in Neutrophils | -0.281 cells x 10^3/L | Standard Deviation 1.5104 |
Primary
Change From Baseline in Neutrophils/Leukocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Neutrophils/Leukocytes | -4.28 percentage of neutrophils in leukocytes | Standard Deviation 5.941 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Neutrophils/Leukocytes | -0.39 percentage of neutrophils in leukocytes | Standard Deviation 6.548 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Neutrophils/Leukocytes | -0.16 percentage of neutrophils in leukocytes | Standard Deviation 8.247 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Neutrophils/Leukocytes | -2.28 percentage of neutrophils in leukocytes | Standard Deviation 7.23 |
| Open-label Extension | Change From Baseline in Neutrophils/Leukocytes | -2.84 percentage of neutrophils in leukocytes | Standard Deviation 7.83 |
Primary
Change From Baseline in Plasma Alanine Aminotransferase
Normal Range: 6 - 41 U/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Alanine Aminotransferase | 0.5 U/L | Standard Deviation 2.7 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Alanine Aminotransferase | 0.8 U/L | Standard Deviation 5.22 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Alanine Aminotransferase | 0.3 U/L | Standard Deviation 3.29 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Alanine Aminotransferase | -1.8 U/L | Standard Deviation 2.95 |
| Open-label Extension | Change From Baseline in Plasma Alanine Aminotransferase | 0.0 U/L | Standard Deviation 3.65 |
Primary
Change From Baseline in Plasma Alkaline Phosphatase
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Alkaline Phosphatase | 10.2 U/L | Standard Deviation 7.08 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Alkaline Phosphatase | -1.0 U/L | Standard Deviation 11.59 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Alkaline Phosphatase | 0.7 U/L | Standard Deviation 15.86 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Alkaline Phosphatase | -1.9 U/L | Standard Deviation 9.45 |
| Open-label Extension | Change From Baseline in Plasma Alkaline Phosphatase | 2.3 U/L | Standard Deviation 12.16 |
Primary
Change From Baseline in Plasma Amylase
Normal range: 22-123 U/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Amylase | 3.1 U/L | Standard Deviation 16.11 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Amylase | 8.9 U/L | Standard Deviation 18.3 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Amylase | 5.0 U/L | Standard Deviation 24.56 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Amylase | 3.9 U/L | Standard Deviation 23.19 |
| Open-label Extension | Change From Baseline in Plasma Amylase | 5.2 U/L | Standard Deviation 20.09 |
Primary
Change From Baseline in Plasma Aspartate Aminotransferase
Normal range : 9-34 U/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Aspartate Aminotransferase | 18.3 U/L | Standard Deviation 6.17 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Aspartate Aminotransferase | -0.4 U/L | Standard Deviation 4.6 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Aspartate Aminotransferase | -3.5 U/L | Standard Deviation 7.71 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Aspartate Aminotransferase | -3.2 U/L | Standard Deviation 3.07 |
| Open-label Extension | Change From Baseline in Plasma Aspartate Aminotransferase | -1.7 U/L | Standard Deviation 5.25 |
Primary
Change From Baseline in Plasma Bicarbonate
Normal range: 21-33 mmol/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Bicarbonate | 0.5 mmol/L | Standard Deviation 3.45 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Bicarbonate | -0.4 mmol/L | Standard Deviation 3.24 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Bicarbonate | 0.9 mmol/L | Standard Deviation 3.59 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Bicarbonate | -0.6 mmol/L | Standard Deviation 2.83 |
| Open-label Extension | Change From Baseline in Plasma Bicarbonate | 0.1 mmol/L | Standard Deviation 3.24 |
Primary
Change From Baseline in Plasma Bilirubin
Normal range: 0.1-1.10 mg/dL
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Bilirubin | 0.044 mg/dL | Standard Deviation 0.1985 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Bilirubin | -0.006 mg/dL | Standard Deviation 0.2796 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Bilirubin | 0.160 mg/dL | Standard Deviation 0.2381 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Bilirubin | -0.012 mg/dL | Standard Deviation 0.1519 |
| Open-label Extension | Change From Baseline in Plasma Bilirubin | 0.050 mg/dL | Standard Deviation 0.2263 |
Primary
Change From Baseline in Plasma Calcium
Normal range: 8.5-10.5 mg/dL
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Calcium | 0.18 mg/dL | Standard Deviation 0.387 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Calcium | 0.20 mg/dL | Standard Deviation 0.427 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Calcium | 0.17 mg/dL | Standard Deviation 0.498 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Calcium | -0.01 mg/dL | Standard Deviation 0.454 |
| Open-label Extension | Change From Baseline in Plasma Calcium | 0.14 mg/dL | Standard Deviation 0.434 |
Primary
Change From Baseline in Plasma Chloride
Normal range: 95-110 mmol/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Chloride | -0.5 mmol/L | Standard Deviation 2.7 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Chloride | 0.9 mmol/L | Standard Deviation 1.79 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Chloride | -0.8 mmol/L | Standard Deviation 3.31 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Chloride | 3.2 mmol/L | Standard Deviation 2.33 |
| Open-label Extension | Change From Baseline in Plasma Chloride | 0.6 mmol/L | Standard Deviation 2.97 |
Primary
Change From Baseline in Plasma Cholesterol
Normal range: 100-200 mg/dL
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Cholesterol | -2.7 mg/dL | Standard Deviation 31.11 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Cholesterol | -2.0 mg/dL | Standard Deviation 27.67 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Cholesterol | 18.9 mg/dL | Standard Deviation 48.17 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Cholesterol | -43.0 mg/dL | Standard Deviation 64.17 |
| Open-label Extension | Change From Baseline in Plasma Cholesterol | -5.6 mg/dL | Standard Deviation 47.99 |
Primary
Change From Baseline in Plasma C Reactive Protein
Normal range: 0.0-3.0 mg/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma C Reactive Protein | 1.200 mg/L | Standard Deviation 3.1597 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma C Reactive Protein | 2.144 mg/L | Standard Deviation 8.5528 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma C Reactive Protein | -1.000 mg/L | Standard Deviation 4.6448 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma C Reactive Protein | -1.444 mg/L | Standard Deviation 3.8014 |
| Open-label Extension | Change From Baseline in Plasma C Reactive Protein | 0.260 mg/L | Standard Deviation 5.4276 |
Primary
Change From Baseline in Plasma Creatine Kinase
Normal range: 23-210 U/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Creatine Kinase | 21.2 U/L | Standard Deviation 39.65 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Creatine Kinase | 18.1 U/L | Standard Deviation 59.2 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Creatine Kinase | -19.5 U/L | Standard Deviation 89.93 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Creatine Kinase | 14.2 U/L | Standard Deviation 206.95 |
| Open-label Extension | Change From Baseline in Plasma Creatine Kinase | 11.9 U/L | Standard Deviation 89.15 |
Primary
Change From Baseline in Plasma Creatinine
Normal range: 0.62-1.44 mg/dL
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Creatinine | 0.060 mg/dL | Standard Deviation 0.1437 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Creatinine | 0.033 mg/dL | Standard Deviation 0.2461 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Creatinine | 0.115 mg/dL | Standard Deviation 0.2186 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Creatinine | 0.147 mg/dL | Standard Deviation 0.379 |
| Open-label Extension | Change From Baseline in Plasma Creatinine | 0.161 mg/dL | Standard Deviation 0.3926 |
Primary
Change From Baseline in Plasma Cystatin C
Normal range: 0.53-0.95 mg/L
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Cystatin C | 0.114 mg/L | Standard Deviation 0.1838 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Cystatin C | 0.104 mg/L | Standard Deviation 0.1074 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Cystatin C | 0.093 mg/L | Standard Deviation 0.2896 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Cystatin C | 0.018 mg/L | Standard Deviation 0.2198 |
| Open-label Extension | Change From Baseline in Plasma Cystatin C | 0.087 mg/L | Standard Deviation 0.2436 |
Primary
Change From Baseline in Plasma Direct Bilirubin
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Direct Bilirubin | 0.011 mg/dL | Standard Deviation 0.0396 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Direct Bilirubin | 0.008 mg/dL | Standard Deviation 0.0316 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Direct Bilirubin | 0.005 mg/dL | Standard Deviation 0.0497 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Direct Bilirubin | -0.005 mg/dL | Standard Deviation 0.0254 |
| Open-label Extension | Change From Baseline in Plasma Direct Bilirubin | 0.004 mg/dL | Standard Deviation 0.0373 |
Primary
Change From Baseline in Plasma Glucose
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Glucose | -5.3 mg/dL | Standard Deviation 15.11 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Glucose | 1.1 mg/dL | Standard Deviation 10.58 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Glucose | 1.5 mg/dL | Standard Deviation 16.91 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Glucose | -6.2 mg/dL | Standard Deviation 14.07 |
| Open-label Extension | Change From Baseline in Plasma Glucose | -0.9 mg/dL | Standard Deviation 14.27 |
Primary
Change From Baseline in Plasma HDL Cholesterol
HDL -High-density lipoprotein
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma HDL Cholesterol | 0.8 mg/dL | Standard Deviation 5.75 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma HDL Cholesterol | -2.3 mg/dL | Standard Deviation 12.95 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma HDL Cholesterol | 2.1 mg/dL | Standard Deviation 20.41 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma HDL Cholesterol | 2.4 mg/dL | Standard Deviation 9.65 |
| Open-label Extension | Change From Baseline in Plasma HDL Cholesterol | 0.7 mg/dL | Standard Deviation 9.39 |
Primary
Change From Baseline in Plasma Indirect Bilirubin
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Indirect Bilirubin | 0.043 mg/dL | Standard Deviation 0.1033 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Indirect Bilirubin | -0.009 mg/dL | Standard Deviation 0.0919 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Indirect Bilirubin | 0.054 mg/dL | Standard Deviation 0.2866 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Indirect Bilirubin | -0.043 mg/dL | Standard Deviation 0.1572 |
| Open-label Extension | Change From Baseline in Plasma Indirect Bilirubin | 0.046 mg/dL | Standard Deviation 0.1947 |
Primary
Change From Baseline in Plasma LDL Cholesterol
LDL - Low-density lipoprotein
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma LDL Cholesterol | 12.2 mg/dL | Standard Deviation 19.97 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma LDL Cholesterol | -2.8 mg/dL | Standard Deviation 11.36 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma LDL Cholesterol | 8.0 mg/dL | Standard Deviation 24.86 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma LDL Cholesterol | -8.9 mg/dL | Standard Deviation 37.78 |
| Open-label Extension | Change From Baseline in Plasma LDL Cholesterol | -5.0 mg/dL | Standard Deviation 37.61 |
Primary
Change From Baseline in Plasma Magnesium
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Magnesium | 0.10 mg/dL | Standard Deviation 0.148 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Magnesium | 0.02 mg/dL | Standard Deviation 0.14 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Magnesium | -0.02 mg/dL | Standard Deviation 0.24 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Magnesium | 0.09 mg/dL | Standard Deviation 0.321 |
| Open-label Extension | Change From Baseline in Plasma Magnesium | 0.01 mg/dL | Standard Deviation 0.199 |
Primary
Change From Baseline in Plasma Pancreatic Lipase
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Pancreatic Lipase | 3.6 U/L | Standard Deviation 9.71 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Pancreatic Lipase | 8.1 U/L | Standard Deviation 24.14 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Pancreatic Lipase | -5.2 U/L | Standard Deviation 9.81 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Pancreatic Lipase | 24.5 U/L | Standard Deviation 51.5 |
| Open-label Extension | Change From Baseline in Plasma Pancreatic Lipase | 9.0 U/L | Standard Deviation 50.27 |
Primary
Change From Baseline in Plasma Phosphate
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Phosphate | 0.33 mg/dL | Standard Deviation 0.609 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Phosphate | 0.16 mg/dL | Standard Deviation 0.423 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Phosphate | 0.15 mg/dL | Standard Deviation 0.596 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Phosphate | 0.04 mg/dL | Standard Deviation 0.803 |
| Open-label Extension | Change From Baseline in Plasma Phosphate | 0.04 mg/dL | Standard Deviation 0.58 |
Primary
Change From Baseline in Plasma Potassium
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Potassium | 0.09 mmol/L | Standard Deviation 0.327 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Potassium | 0.12 mmol/L | Standard Deviation 0.232 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Potassium | -0.09 mmol/L | Standard Deviation 0.305 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Potassium | 0.23 mmol/L | Standard Deviation 0.789 |
| Open-label Extension | Change From Baseline in Plasma Potassium | 0.00 mmol/L | Standard Deviation 0.514 |
Primary
Change From Baseline in Plasma Protein
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Protein | 0.17 g/dL | Standard Deviation 0.32 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Protein | 0.05 g/dL | Standard Deviation 0.305 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Protein | -0.11 g/dL | Standard Deviation 0.575 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Protein | -0.09 g/dL | Standard Deviation 0.396 |
| Open-label Extension | Change From Baseline in Plasma Protein | 0.00 g/dL | Standard Deviation 0.515 |
Primary
Change From Baseline in Plasma Sodium
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Sodium | 0.0 mmol/L | Standard Deviation 2.22 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Sodium | 1.8 mmol/L | Standard Deviation 3.89 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Sodium | 0.9 mmol/L | Standard Deviation 3.59 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Sodium | 2.5 mmol/L | Standard Deviation 5.05 |
| Open-label Extension | Change From Baseline in Plasma Sodium | 1.0 mmol/L | Standard Deviation 3.46 |
Primary
Change From Baseline in Plasma Triglycerides
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Triglycerides | 16.6 mg/dL | Standard Deviation 123.84 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Triglycerides | 5.7 mg/dL | Standard Deviation 51.48 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Triglycerides | -16.5 mg/dL | Standard Deviation 25.8 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Triglycerides | -23.2 mg/dL | Standard Deviation 123.79 |
| Open-label Extension | Change From Baseline in Plasma Triglycerides | -2.6 mg/dL | Standard Deviation 80.08 |
Primary
Change From Baseline in Plasma Urate
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Urate | 0.51 mg/dL | Standard Deviation 0.485 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Urate | 0.04 mg/dL | Standard Deviation 1.107 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Urate | -0.28 mg/dL | Standard Deviation 0.877 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Urate | -0.08 mg/dL | Standard Deviation 0.926 |
| Open-label Extension | Change From Baseline in Plasma Urate | -0.05 mg/dL | Standard Deviation 1.04 |
Primary
Change From Baseline in Plasma Urea Nitrogen
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Plasma Urea Nitrogen | 2.8 mg/dL | Standard Deviation 3.65 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Plasma Urea Nitrogen | -2.6 mg/dL | Standard Deviation 4.18 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Plasma Urea Nitrogen | 3.6 mg/dL | Standard Deviation 5.95 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Plasma Urea Nitrogen | 1.1 mg/dL | Standard Deviation 11.42 |
| Open-label Extension | Change From Baseline in Plasma Urea Nitrogen | 2.3 mg/dL | Standard Deviation 6.15 |
Primary
Change From Baseline in Platelets
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Platelets | 5.2 cells x 10^9/L | Standard Deviation 31.68 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Platelets | 26.2 cells x 10^9/L | Standard Deviation 30.1 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Platelets | 4.8 cells x 10^9/L | Standard Deviation 28.72 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Platelets | 0.9 cells x 10^9/L | Standard Deviation 27.65 |
| Open-label Extension | Change From Baseline in Platelets | 19.1 cells x 10^9/L | Standard Deviation 54.3 |
Primary
Change From Baseline in Prothrombin Intl. Normalised Ratio
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Prothrombin Intl. Normalised Ratio | 0.03 Prothombin intl. normalised ratio | Standard Deviation 0.21 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Prothrombin Intl. Normalised Ratio | 0.01 Prothombin intl. normalised ratio | Standard Deviation 0.16 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Prothrombin Intl. Normalised Ratio | 0.10 Prothombin intl. normalised ratio | Standard Deviation 0.141 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Prothrombin Intl. Normalised Ratio | 0.01 Prothombin intl. normalised ratio | Standard Deviation 0.088 |
| Open-label Extension | Change From Baseline in Prothrombin Intl. Normalised Ratio | 0.08 Prothombin intl. normalised ratio | Standard Deviation 0.387 |
Primary
Change From Baseline in Prothrombin Time
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Prothrombin Time | 0.48 second | Standard Deviation 1.566 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Prothrombin Time | 0.07 second | Standard Deviation 1.561 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Prothrombin Time | 0.69 second | Standard Deviation 1.268 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Prothrombin Time | 0.33 second | Standard Deviation 0.736 |
| Open-label Extension | Change From Baseline in Prothrombin Time | 0.78 second | Standard Deviation 3.445 |
Primary
Change From Baseline in Reticulocytes/Erythrocytes
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Reticulocytes/Erythrocytes | -0.08 percentage of reticulocytes/erythrocytes | Standard Deviation 0.626 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Reticulocytes/Erythrocytes | -0.11 percentage of reticulocytes/erythrocytes | Standard Deviation 0.554 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Reticulocytes/Erythrocytes | -0.30 percentage of reticulocytes/erythrocytes | Standard Deviation 0.615 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Reticulocytes/Erythrocytes | -0.12 percentage of reticulocytes/erythrocytes | Standard Deviation 0.29 |
| Open-label Extension | Change From Baseline in Reticulocytes/Erythrocytes | -0.14 percentage of reticulocytes/erythrocytes | Standard Deviation 0.536 |
Primary
Change From Baseline in UPCR at Week 12
Least squared mean ratio of UPCR (Urine protein g:creatinine g) compared to baseline at Week 12 in the ITT population. ITT- Intent to treat
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in UPCR at Week 12 | 0.83 g protein/g creatinine |
| CCX140-B 5 mg Once Daily | Change From Baseline in UPCR at Week 12 | 1.02 g protein/g creatinine |
| CCX140-B 10 mg Twice Daily | Change From Baseline in UPCR at Week 12 | 1.12 g protein/g creatinine |
| CCX140-B 15 mg Twice Daily | Change From Baseline in UPCR at Week 12 | 0.87 g protein/g creatinine |
p-value: 0.192490% CI: [0.95, 1.6]Mixed effects model for repeated measure
p-value: 0.061290% CI: [1.04, 1.76]Mixed effects model for repeated measure
p-value: 0.765390% CI: [0.81, 1.36]Mixed effects model for repeated measure
p-value: 0.153790% CI: [0.97, 1.48]Mixed effects model for repeated measure
Primary
Change From Baseline in Urine Albumin
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Urine Albumin | 1.117 mg/dL | Standard Deviation 118.7664 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Urine Albumin | -19.044 mg/dL | Standard Deviation 119.7149 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Urine Albumin | -8.455 mg/dL | Standard Deviation 53.9332 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Urine Albumin | -35.964 mg/dL | Standard Deviation 178.9164 |
| Open-label Extension | Change From Baseline in Urine Albumin | -28.433 mg/dL | Standard Deviation 107.8847 |
Primary
Change From Baseline in Urine Creatinine
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Urine Creatinine | 10.65 mg/dL | Standard Deviation 35.931 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Urine Creatinine | -11.67 mg/dL | Standard Deviation 33.432 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Urine Creatinine | -15.37 mg/dL | Standard Deviation 30.92 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Urine Creatinine | 25.30 mg/dL | Standard Deviation 84.654 |
| Open-label Extension | Change From Baseline in Urine Creatinine | -6.96 mg/dL | Standard Deviation 31.53 |
Primary
Change From Baseline in Urine Protein
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Urine Protein | -19.3 mg/dL | Standard Deviation 139.96 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Urine Protein | -8.9 mg/dL | Standard Deviation 134.17 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Urine Protein | -9.0 mg/dL | Standard Deviation 80.51 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Urine Protein | -80.6 mg/dL | Standard Deviation 230.57 |
| Open-label Extension | Change From Baseline in Urine Protein | -35.1 mg/dL | Standard Deviation 144.93 |
Primary
Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs)
TEAEs leading to study withdrawal means study drug discontinuation in this endpoint.
Time frame: Baseline to Week 12, and Week 12 to Week 24
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs | 10 Participants |
| Placebo | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs leading to study withdrawal | 0 Participants |
| Placebo | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| CCX140-B 5 mg Once Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| CCX140-B 5 mg Once Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs | 6 Participants |
| CCX140-B 5 mg Once Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs leading to study withdrawal | 0 Participants |
| CCX140-B 10 mg Twice Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| CCX140-B 10 mg Twice Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs | 8 Participants |
| CCX140-B 10 mg Twice Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs leading to study withdrawal | 1 Participants |
| CCX140-B 15 mg Twice Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| CCX140-B 15 mg Twice Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs leading to study withdrawal | 0 Participants |
| CCX140-B 15 mg Twice Daily | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Open-label Extension | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Open-label Extension | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs | 24 Participants |
| Open-label Extension | Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs) | TEAEs leading to study withdrawal | 2 Participants |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24
Change from baseline in eGFR calculated by the CKD-EPI Cystatin C equation, CKD-EPI Creatinine equation, CKD-EPI Creatinine-Cystatin C equation and MDRD Creatinine equation at Weeks 12 and 24. CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; MDRD: Modification of Diet in Renal Disease Open label extension covers Baseline to Week 12 and Baseline to Week 24
Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 12 | -4.9 mL/min/1.73 m^2 | Standard Deviation 11.74 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 24 | -0.8 mL/min/1.73 m^2 | Standard Deviation 6.63 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 12 | -3.0 mL/min/1.73 m^2 | Standard Deviation 6.47 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 24 | -3.1 mL/min/1.73 m^2 | Standard Deviation 5.74 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 12 | -5.3 mL/min/1.73 m^2 | Standard Deviation 8.92 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 24 | -2.4 mL/min/1.73 m^2 | Standard Deviation 5.24 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 12 | -4.7 mL/min/1.73 m^2 | Standard Deviation 10.82 |
| Placebo | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 24 | -4.5 mL/min/1.73 m^2 | Standard Deviation 11.12 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 12 | -4.2 mL/min/1.73 m^2 | Standard Deviation 11.5 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 24 | -5.5 mL/min/1.73 m^2 | Standard Deviation 9.2 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 12 | -3.1 mL/min/1.73 m^2 | Standard Deviation 3.91 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 24 | -8.2 mL/min/1.73 m^2 | Standard Deviation 9.89 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 24 | -3.2 mL/min/1.73 m^2 | Standard Deviation 10.4 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 24 | -8.8 mL/min/1.73 m^2 | Standard Deviation 12.85 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 12 | -3.5 mL/min/1.73 m^2 | Standard Deviation 5.61 |
| CCX140-B 5 mg Once Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 12 | -5.1 mL/min/1.73 m^2 | Standard Deviation 13.75 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 12 | -4.6 mL/min/1.73 m^2 | Standard Deviation 6.23 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 24 | -5.9 mL/min/1.73 m^2 | Standard Deviation 10.05 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 24 | -5.3 mL/min/1.73 m^2 | Standard Deviation 10.59 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 24 | -3.2 mL/min/1.73 m^2 | Standard Deviation 9.18 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 12 | -3.9 mL/min/1.73 m^2 | Standard Deviation 5.74 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 24 | -1.3 mL/min/1.73 m^2 | Standard Deviation 9.69 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 12 | -1.6 mL/min/1.73 m^2 | Standard Deviation 8.61 |
| CCX140-B 10 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 12 | -2.6 mL/min/1.73 m^2 | Standard Deviation 6.53 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 24 | -3.2 mL/min/1.73 m^2 | Standard Deviation 9.6 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 12 | -4.8 mL/min/1.73 m^2 | Standard Deviation 9.68 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 24 | -2.0 mL/min/1.73 m^2 | Standard Deviation 8.29 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 12 | -2.8 mL/min/1.73 m^2 | Standard Deviation 8.57 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 24 | -2.8 mL/min/1.73 m^2 | Standard Deviation 7.93 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 24 | -4.0 mL/min/1.73 m^2 | Standard Deviation 10.77 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 12 | 0.2 mL/min/1.73 m^2 | Standard Deviation 9.51 |
| CCX140-B 15 mg Twice Daily | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 12 | -6.7 mL/min/1.73 m^2 | Standard Deviation 14.03 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 24 | -4.7 mL/min/1.73 m^2 | Standard Deviation 8.8 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 24 | -5.8 mL/min/1.73 m^2 | Standard Deviation 10.95 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine equation Week 12 | -4.7 mL/min/1.73 m^2 | Standard Deviation 9.68 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | MDRD Creatinine equation Week 12 | -5.6 mL/min/1.73 m^2 | Standard Deviation 13.76 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 12 | -1.7 mL/min/1.73 m^2 | Standard Deviation 9.49 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 24 | -3.4 mL/min/1.73 m^2 | Standard Deviation 7.82 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Cystatin C equation Week 24 | -2.0 mL/min/1.73 m^2 | Standard Deviation 8.86 |
| Open-label Extension | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24 | CKD-EPI Creatinine-Cystatin C equation Week 12 | -3.2 mL/min/1.73 m^2 | Standard Deviation 8.43 |
Secondary
Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24
1\. Proportion of subjects achieving complete renal remission by the following definition at Weeks 12 and 24 o Reduction in UPCR to \<0.3 g/g o Serum albumin within normal range (for subjects with abnormal serum creatinine levels at baseline, return to normal levels for that age group; for subjects with normal serum creatinine levels at baseline, final value within 20% of baseline levels) 2. Proportion of subjects achieving partial remission defined as UPCR reduction of ≥50% from baseline and UPCR \<3.5 g/g (definition 1), assessed at Weeks 12 and 24 3. Proportion of subjects achieving partial remission defined Decrease in UPCR to less than 1.5 g/g and at least a 40% reduction in proteinuria from baseline (definition 2), assessed at Weeks 12 and 24
Time frame: Endpoint at Week 12 for Double-Blind Treatment Period and Endpoint at Week 24 for Open-Label Extension
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Complete renal remission | 0 Participants |
| Placebo | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 2) | 0 Participants |
| Placebo | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 1) | 1 Participants |
| CCX140-B 5 mg Once Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 1) | 0 Participants |
| CCX140-B 5 mg Once Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Complete renal remission | 0 Participants |
| CCX140-B 5 mg Once Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 2) | 0 Participants |
| CCX140-B 10 mg Twice Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 1) | 0 Participants |
| CCX140-B 10 mg Twice Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Complete renal remission | 0 Participants |
| CCX140-B 10 mg Twice Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 2) | 0 Participants |
| CCX140-B 15 mg Twice Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Complete renal remission | 0 Participants |
| CCX140-B 15 mg Twice Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 2) | 0 Participants |
| CCX140-B 15 mg Twice Daily | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 1) | 1 Participants |
| Open-label Extension | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 1) | 4 Participants |
| Open-label Extension | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Complete renal remission | 0 Participants |
| Open-label Extension | Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24 | Partial remission (definition 2) | 6 Participants |