Focal Segmental Glomerulosclerosis (FSGS) MedDRA version: 20.0 Level: PT Classification code 10067757 Term: Focal segmental glomerulosclerosis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
ChemoCentryx, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged 18-75 years inclusive 2. Urinary total protein:creatinine ration (UPCR) = 1 g protein/g creatinine at screening (or UPCR at 113 mg/mmol). 3. Diagnosis of FSGS based on at least one of the following: o Renal biopsy demonstrating the FSGS lesion and characteristic clinical presentation and course o High risk genetic variant and characteristic clinical presentation and course 4. Diagnosis of one of the following subtypes of FSGS: o Primary FSGS based on characteristic histopathology, medical history, and clinical course, or o FSGS secondary to a genetic variant associated with increased risk or severity, which may include NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 or INF2 5. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73m2, with eGFR calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (using creatinine or cystatin C) 6. The typical blood pressure of the patient should be clinically stable prior to enrollment and not exceed 145/95 mmHg. 7. If using RAAS blockers, dose must be stable for a minimum of 4 weeks prior to Screening, and projected to remain stable through Study Week 12, unless adjustment is required for management of hypertension. Blood pressure should be clinically stable prior to enrollment. 8. If using immunosuppressive or immunomodulatory therapy, dose must be stable for a minimum of 4 weeks prior to Screening, and projected to remain stable through Study Week 12 9. If using glucocorticoids, dose must be stable for a minimum of 4 weeks prior to Screening and projected to remain stable through Study Week 12 10. Female subjects of childbearing potential may participate if adequate contraception is used during, and for at least 5 half-lives after last dose of study drug. 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 one month after the last dose of study drug. 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 sexual abstinence). In addition, a barrier method (i.e. cervical cap, diaphragm or condom) must be used during intercourse between a male subject and a female of child-bearing potential. 11. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol 12. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Pregnant or nursing 2. History of organ transplantation 3. Currently on an organ transplant waiting list or there’s a reasonable possibility of getting an organ transplant within 6 months of screening 4. Subjects that use of rituximab or other anti-CD20 monoclonal antibodies within 20 weeks prior to screening are excluded while subjects that used rituximab or other anti-CD20 monoclonal antibodies prior to 20 week of screening are allowed with confirmed recovery of CD20+ B cell population to within normal range 5. Plasmapheresis within 12 weeks prior to screening 6. Body mass index (BMI) =40 7. Participated in any clinical study of an investigational product within 12 weeks prior to screening, or within 5 half-lives after taking the last dose of investigational product 8. Currently on dialysis or likely to require dialysis during the projected blinded treatment period of 12 weeks 9. History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis 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 (e.g. lupus nephritis, C3 glomerulopathy, proliferative glomerulonephritis, IgA nephropathy, reflux nephropathy, surgical segmental renal ablation, sickle cell disease ) that is active, or has significant risk of progressing during the course of the study 12. Disorders other than those listed in Inclusion Criterion 4 that are associated with FSGS lesion (e.g. single kidney, surgical segmental renal ablation, sickle cell disease, diabetic nephropathy; others) 13. Evidence of tuberculosis based on interferon ? release assay (IGRA), tuberculin purified protein derivative (PPD) skin test, or chest radiography done during screening or within 6 weeks prior to screening 14. Evidence of hepatic disease; AST, ALT, alkaline phosphatase >3x ULN, or total bilirubin > 2x ULN or INR > 1.5 x ULN at baseline prior to dosing 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. Clinically significant peripheral neuropathy. 16. Hematologic abnormalities as follows: Hb < 8 g/dL, platelets < 50,000, ANC < 1000 cells/µL) at baseline 17. Clinically significant abnormal ECG during screening, e.g., QTcF greater than 450 msec 18. History of alcohol or illicit drug abuse or of lithium, pamidronate and interferon. Recreational use of cannabis is not excluded where legal. 19. History of gastrointestinal conditions that may interfere with study medication compliance, e.g., severe gastroparesis, with regurgitation of food or oral medication 20. Known hypersensitivity to CCX140-B or inactive ingredients of the CCX140-B tablets (including microcrystalline cellulose, starch, crospovidone, magnesium stearate, or silicon dioxide) 21. 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 gluco
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • The primary safety objective of this study is to evaluate the safety and tolerability of CCX140-B in subjects with FSGS with proteinuria. • The primary efficacy objective of this study is to evaluate the effect of CCX140-B treatment on urinary protein excretion in subjects with FSGS, as assessed by change from baseline in the urine protein to creatinine ratio (UPCR).;Secondary Objective: • To evaluate the effect of CCX140-B on renal function, as assessed by estimated glomerular filtration rate (eGFR); • To evaluate the pharmacokinetic (PK) profile of CCX140-B in subjects with FSGS.;Primary end point(s): Efficacy: Change from baseline in urine protein:creatinine ratio (UPCR) at week 12 Safety: • Subject incidence of treatment-emergent adverse events, adverse events leading to study withdrawal, and serious adverse events; • Change from baseline and shifts from baseline in all safety laboratory parameters; • Change from baseline in vital signs; • Change form baseline in score on the ACTG BPNST • Clinically significant abnormal ECG findings • Physical examinations;Timepoint(s) of evaluation of this end point: Efficacy: Week 12, Week 24 Safety: Day1, Week12, Week16, Week24, Week28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • 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 assessed at Weeks 12 and 24 • Proportion of subjects achieving complete renal remission (UPCR 0.3 g/g: eGFR normal or not less than 20% below baseline) or partial remission (UPCR decreased by 50% from baseline; UPCR <3.5g/g; and eGFR normal or not less than 20% below baseline), assessed at Weeks 12 and 24.;Timepoint(s) of evaluation of this end point: Efficacy: Weeks 12, Week 24 | — |
Countries
Australia, Canada, Czech Republic, France, Germany, Italy, New Zealand, Poland, United Kingdom, United States
Contacts
Public ContactRegulatory Submissions
Medpace Germany GmbH
Outcome results
None listed