|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Primary Focal Segmental Glomerulosclerosis (FSGS)
|Medical condition in easily understood language
|A type of glomerular disease (disease damaging the glomeruli, the filtering units inside the kidney where blood is cleaned) that causes scarring (sclerosis) in kidney.
|Diseases [C] - Immune System Diseases [C20]
|E.1.2 Medical condition or disease under investigation
|Focal segmental glomerulosclerosis
|System Organ Class
|10038359 - Renal and urinary disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The Primary Efficacy Objective is to evaluate the effect of CCX140-B on proteinuria in subjects with primary FSGS with nephrotic syndrome.
|Secondary objectives of the trial
|1. Achievement of partial or complete remission of urine protein to creatinine ratio (UPCR) through Study Week 12 and through the end of treatment,
2. Assessment of change from baseline in UPCR over time
3. Assessment of time to, and proportion of subjects with achievement of partial remission
4. Assessment of time to, and proportion of subjects with achievement of complete remission
5. Assessment of time to rescue therapy, based on Investigator or physician initiation of glucocorticoids or new immunosuppressive agents or new major treatment modalities
6. Changes over time in other laboratory parameters related to renal function, including:
• Serum albumin
• Cystatin C
• eGFR, calculated by the CKD-EPI Cystatin C equation, CKD-EPI Creatinine equation, CKD-EPI Creatinine-Cystatin C equation and MDRD Creatinine equation.
• urine albumin to creatinine ratio (UACR)
• total 24 hour urine protein excretion
7. Quality of Life endpoints using SF-36 v2 and EQ-5D-5L
|Trial contains a sub-study
|Principal inclusion criteria
|1. Male or female subjects aged 18 years and older
2. Renal biopsy findings consistent with diagnosis of focal segmental glomerulosclerosis (FSGS), and consistent with primary FSGS based on presentation of histopathology, medical history, and clinical course; subjects with genetic risk factors with presentations that are otherwise consistent with primary FSGS may also be enrolled.
3. Urinary total protein:creatinine ratio (UPCR) ≥ 3.5 g protein/g creatinine at screening, based on sample drawn from a 24-hour collection
4. Hypoalbuminemia of less than 3.5 g/dL
5. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73m2, as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD_EPI) equation (using creatinine or cystatin C)
6. If used, RAAS inhibitor dose, including doses of angiotensin converting enzyme inhibitor and/or angiotensin II receptor antagonist must have been started at least 4 weeks prior to Study Day 1, and projected to remain stable throughout the course of the study unless adjustment is required for management of hypertension.
7. 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.
8. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol
9. 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.
|Principal exclusion criteria
|1. Pregnant or nursing
2. History of organ transplantation, including renal 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. Histological FSGS subtype of collapsing variant
5. Subjects who initiated, discontinued or changed dose of rituximab or other anti-CD20 monoclonal antibodies within 16 weeks (4 months) prior to screening are excluded. Subjects who initiated treatment with rituximab or other anti-CD20 monoclonal antibodies >16 weeks (4 months) prior to screening are permitted if deemed safe by the investigator and only if they are intended to remain on continued, unchanged therapy at a dosing interval that has been documented to achieve continuous B cell depletion for the given patient. UPCR and other urine protein assessments up to 1 year prior to screening (if available) that were performed in these patients as part of the clinical routine should be recorded in the medical history.
6. Subjects who discontinued Rituximab or other anti-CD20 monoclonal antibodies >16 weeks (4 months) prior to screening without confirmed recovery of CD20+ B cell population to within normal range are excluded. Subjects who discontinued rituximab or other anti-CD20 monoclonal antibodies >16 weeks (4 months) prior to screening with confirmed recovery of CD20+ B cell population to within normal range are permitted in the study. UPCR and other urine protein assessments up to 1 year prior to screening (if available) that were performed in these patients as part of the clinical routine should be recorded in the medical history.
7. Subjects who initiated or increased the dose of calcineurin inhibitors, or other immunotherapy, within 12 weeks prior to screening are excluded; dose reductions to maintain calcineurin inhibitors at optimal safe levels are permitted. Subjects who initiated a treatment with calcineurin inhibitors, or other immunotherapy >12 weeks are permitted. UPCR and other urine protein assessments up to 1 year prior to screening (if available) that were performed in these patients as part of the clinical routine should be recorded in the medical history.
8. Subjects taking glucocorticoids at dose greater than 10 mg/day prednisone equivalent within 4 weeks prior to screening are excluded.
9. Plasmapheresis within 12 weeks prior to screening
10. Body Mass Index (BMI) ≥ 40
11. 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
12. Currently on dialysis or likely to require dialysis during the study
13. 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
14. 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 weeks prior to screening
15. Evidence of tuberculosis based on interferon γ release assay (IGRA), tuberculin purified protein derivative (PPD) skin test, or chest radiography done during screening or within 6 weeks prior to screening
16. Evidence of hepatic disease; AST, ALT, alkaline phosphatase >2x ULN, or total bilirubin > 2x ULN or INR > 1.5 x ULN at screening with the exception that isolated INR elevation in the absence of other significant liver enzyme abnormalities is explained by anticoagulant therapy, (e.g. warfarin).
17. Clinically significant peripheral neuropathy
18. Hematologic abnormalities as follows: Hb <8 g/dL, platelets <50,000, ANC <1000 cells/μL) at baseline
19. Abnormality of ECG at screening, assessed by the Investigator as clinically significant (e.g. QTcF greater than 450 msec).
20. History of alcohol or illicit drug abuse. Recreational use of cannabis is not excluded where legalized.
21. History of gastrointestinal conditions that may interfere with study medication compliance, e.g., severe gastroparesis, with regurgitation of food or oral medication
22. Known hypersensitivity to CCX140-B or inactive ingredients of the CCX140-B tablets (including microcrystalline cellulose, starch, crospovidone, magnesium stearate, or silicon dioxide)
23. Renal disease associated with disorders other than FSGS (e.g. lupus nephritis, C3 glomerulonephropathy) that is active, or has significant risk of progressing to end state renal disease during the 12-week initial treatment phase of the study
Full list of exclusion criteria is in the protocol
|E.5 End points
|Primary end point(s)
|Evaluate the effect of CCX140-B on proteinuria in subjects with primary FSGS with nephrotic syndrome.
|Timepoint(s) of evaluation of this end point
|Assessed as a median reduction from baseline of urine protein to creatinine ratio (UPCR) of at least 20%, i.e. ≥ 20%, by week 12.
|Secondary end point(s)
|Secondary endpoints include:
• Achievement of Partial Remission (includes all of the following) reduction from baseline by ≥50 percent in UPCR reduction in UPCR to a level that is < 3.5 g/g at week 12 subject may not be a treatment failure
• Achievement of Complete Remission (includes all of the following) at week 12
- reduction in UPCR to < 0.3 g/g
- serum albumin within normal range
- for patients with abnormal serum creatinine levels at baseline, return to normal levels for that age group
- for patients with normal serum creatinine levels at baseline, final value within 20% of baseline levels
- subject may not be a treatment failure
• Change from baseline of UPCR in subjects treated with CCX140-B over time
• The proportion of subjects with partial remission at any time during the treatment period.
• The proportion of subjects with complete remission at any time during the treatment period.
• Time to Partial Remission (PR) or Complete Remission (CR)
• Change from baseline in renal function, based on eGFR (calculated using the CKD-EPI Cystatin C equation (Dharnidharka VR, et al, 2002), the CKD-EPI Creatinine equation (Schwartz GJ, et al. 2016, Selistre L et al 2016), CKD-EPI Creatinine-Cystatin C equation (Stevens et al., 2008) and MDRD Creatinine equation (Levey et al. 1999, Levey et al. 2006) over time
• Change over time in total 24 hour urine protein excretion
• Change from baseline in serum albumin over time
• Change in UACR from baseline over time
• Time to investigator or physician initiation of rescue therapy including glucocorticoids, new immunosuppressive agents or new major treatment modalities (e.g. plasmapheresis, dialysis)
• Duration between achievement of remission and relapse or treatment failure
• Changes over time in Health Quality Assessment (SF-36 v2 and EQ-5D-5L)
|Timepoint(s) of evaluation of this end point
|Secondary efficacy endpoints of this study will be assessed through Study Week 12 and through End of Treatment.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months