A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome

Phase 2

Terminated

Conditions: Focal Segmental Glomerulosclerosis

Interventions: Drug: CCX140-B

Registration Number: NCT03703908

Lead Sponsor: Amgen

Brief Summary: An Open Label, Intra-Subject Dose Escalation Study of CCX140 B in Subjects with Primary FSGS and Nephrotic Syndrome

Detailed Description: An Open Label, Intra-Subject Dose Escalation Study of CCX140 B in Subjects with Primary Focal Segmental Glomerulosclerosis (FSGS) and Nephrotic Syndrome. The aim of this study is to explore the effect of CCX140-B, a selective antagonist of C-C chemokine receptor type 2, on proteinuria in subjects with FSGS.

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Male or female subjects aged 18 years and older
Primary FSGS based on renal biopsy findings consistent with FSGS and based on presentation of histopathology, medical history and clinical course OR subjects with genetic risk factors with presentations that are otherwise consistent with primary FSGS
Urinary total protein:creatinine ratio (UPCR) ≥ 3.5 g protein/g creatinine at screening

Exclusion Criteria

Pregnant or nursing
History of organ transplantation, including renal transplantation
Currently on an organ transplant waiting list or there's a reasonable possibility of getting an organ transplant within 6 months of screening
Histological FSGS subtype of collapsing variant
Subjects who initiated, discontinued or changed dose of anti-CD20 monoclonal antibodies within 16 weeks (4 months) prior to screening are excluded. Subjects who initiated treatment with anti-CD20 monoclonal antibodies >16 weeks (4 months) prior to screening are permitted if deemed safe by the investigator and only if they intend to remain on continued, unchanged therapy at a dosing interval that has been documented to achieve continuous B cell depletion for the given patient.
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.
Body Mass Index (BMI) ≥ 40

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Sequential	CCX140-B	All enrolled subjects will initially be treated with the active study medication CCX140-B at a dose of 5 mg twice daily. Dose will increase in a step-wise fashion up to 15 mg twice daily.

Primary Outcome Measures

Name	Time	Method
The Number of Subjects With a Reduction in Urine Protein to Creatinine Ratio (UPCR) of at Least 20%	Baseline to week 12	Number of subjects with a reduction in Urine Protein to Creatinine Ratio (UPCR) of at least 20% , i.e., ≥20%, by Week 12.

Secondary Outcome Measures

Name	Time	Method
Achievement of Partial or Complete Remission of UPCR Through Week 12 and Through the End of Treatment	Baseline to week 12	Partial and complete remission were defined as follows: Partial remission (included all of the following): * Reduction from baseline by ≥50% in urine protein:creatinine ratio (UPCR) * Reduction in UPCR to a level that was \<3.5 g/g * Subject could not have been a treatment failure Complete remission (included all of the following): * Reduction in UPCR to \<0.3 g/g * Serum albumin within normal range * For subjects with abnormal serum creatinine levels at baseline, return to normal levels * For subjects with normal serum creatinine levels at baseline, final value within 20% of baseline levels * Subject could not have been a treatment failure
Proportion of Subjects With Achievement of Complete Remission During the Treatment Period	Baseline to week 52	Complete remission is defined as reduction in urine protein:creatinine ratio (UPCR) to \<0.3 g/g, normal serum albumin, and normal serum creatinine levels or within 20% of baseline levels.
Time Taken of Subjects to Achieve Complete Remission During the Treatment Period	Baseline to week 52	Complete remission is defined as reduction in urine protein:creatinine ratio (UPCR) to \<0.3 g/g, normal serum albumin, and normal serum creatinine levels or within 20% of baseline levels.
Change From Baseline in Urine Protein:Creatinine Ratio (UPCR) Over Time	Baseline to week 12 and week 52	Mean change from baseline in urinary protein:creatinine ratio (UPCR) over time.
Assessment of Time to and Proportion of Subjects With Achievement of Partial Remission During the Treatment Period	Baseline to week 52	Partial remission is defined as reduction from baseline by ≥50% in UPCR, reduction in UPCR to a level that was \<3.5 g/g.
Time to Rescue Therapy	Baseline to week 52	Based on Investigator or physician initiation of glucocorticoids or new immunosuppressive agents or new major treatment modalities (e.g. plasmapheresis, dialysis)
Mean Change From Baseline for eGFR Using the CKD-EPI Cystatin C Equation Over Time	Baseline to Week 12 and Week 52	eGFR-Estimated Glomerular Filtration Rate;CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration
Mean Change From Baseline for the eGFR CKD-EPI Creatinine Equation Over Time	Baseline to Week 12 and Week 52	CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate
Mean Change From Baseline for eGFR CKD-EPI Creatinine-Cystatin C Equation Over Time	Baseline to Week 12 and Week 52	CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate;
Mean Change From Baseline for the MDRD Creatinine Equation Over Time	Baseline to Week 12 and Week 52	MDRD = Modification of Diet in Renal Disease. The mean eGFR (using the MDRD Creatinine equation) change from baseline to Week 12 and Week 52
Effect of CCX140-B Treatment on Quality of Life Endpoint SF-36V2	Baseline to Week 52	Summary of the Effect of CCX140-B Treatment on Quality of Life Endpoints SF-36V2 for the overall trial SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health).
Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the Overall Trial	Baseline to Week 12 and Week 52	Summary of the Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the overall trial EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of : the EQ-5D descriptive system. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine.
Changes to Laboratory Parameters Related to Renal Function Including Serum Albumin, Creatinine, Cystatin C, Urinary Albumin:Creatinine Ratio, Total 24-hour Protein Excretion During the Trial	Baseline to Day 57	Changes to laboratory parameters related to renal function including serum albumin, creatinine, cystatin C, urinary albumin:creatinine ratio, total 24-hour protein excretion during the trial

Trial Locations

Locations (5): Los Angeles Biomedical Research Institute
🇺🇸
Torrance, California, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Utah Kidney Research Institute
🇺🇸
Salt Lake City, Utah, United States
Northwest Louisiana Nephrology
🇺🇸
Shreveport, Louisiana, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States