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

An Open Label, Intra-Subject Dose Escalation Study of CCX140-B in Subjects With Primary Focal Segmental Glomerulosclerosis (FSGS) and Nephrotic Syndrome

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

Study Overview

• Status: Terminated
• Conditions: Focal Segmental Glomerulosclerosis
• Intervention / Treatment: Drug: CCX140-B

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota
  • Utah
    • Salt Lake City, Utah, United States, 84115
      • Utah Kidney Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects aged 18 years and older
2. 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
3. Urinary total protein:creatinine ratio (UPCR) ≥ 3.5 g protein/g creatinine at screening

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 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.
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. Body Mass Index (BMI) ≥ 40

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential; 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.	Drug: CCX140-B; Orally administered tablet

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of Partial or Complete Remission of UPCR Through Week 12 and Through the End of Treatment	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	Baseline to week 12
Proportion of Subjects With Achievement of Complete Remission During the Treatment Period	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.	Baseline to week 52
Time Taken of Subjects to Achieve Complete Remission During the Treatment Period	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.	Baseline to week 52
Change From Baseline in Urine Protein:Creatinine Ratio (UPCR) Over Time	Mean change from baseline in urinary protein:creatinine ratio (UPCR) over time.	Baseline to week 12 and week 52
Assessment of Time to and Proportion of Subjects With Achievement of Partial Remission During the Treatment Period	Partial remission is defined as reduction from baseline by ≥50% in UPCR, reduction in UPCR to a level that was <3.5 g/g.	Baseline to week 52
Time to Rescue Therapy	Based on Investigator or physician initiation of glucocorticoids or new immunosuppressive agents or new major treatment modalities (e.g. plasmapheresis, dialysis)	Baseline to week 52
Mean Change From Baseline for eGFR Using the CKD-EPI Cystatin C Equation Over Time	eGFR-Estimated Glomerular Filtration Rate;CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration	Baseline to Week 12 and Week 52
Mean Change From Baseline for the eGFR CKD-EPI Creatinine Equation Over Time	CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate	Baseline to Week 12 and Week 52
Mean Change From Baseline for eGFR CKD-EPI Creatinine-Cystatin C Equation Over Time	CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; eGFR = estimated glomerular filtration rate;	Baseline to Week 12 and Week 52
Mean Change From Baseline for the MDRD Creatinine Equation Over Time	MDRD = Modification of Diet in Renal Disease. The mean eGFR (using the MDRD Creatinine equation) change from baseline to Week 12 and Week 52	Baseline to Week 12 and Week 52
Effect of CCX140-B Treatment on Quality of Life Endpoint SF-36V2	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).	Baseline to Week 52
Effect of CCX140-B Treatment on Quality of Life Endpoint EQ-5D-5L for the Overall Trial	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.	Baseline to Week 12 and Week 52
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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in EKG values	Triplicate EKGs assessed for any clinically significant abnormalities as determined by the relevant PIs evaluation	Baseline to each subsequent clinic visit through week 52
Changes from baseline in blood pressure	Assessment of systolic and diastolic BP changes from baseline	Baseline to each subsequent clinic visit through week 52

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• Company Website

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): June 24, 2020
• Study Completion (Actual): June 24, 2020

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: October 9, 2018
• First Posted (Actual): October 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Proteinuria; FSGS; Glomerulosclerosis
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Glomerulonephritis; Nephritis; Nephrotic Syndrome; Nephrosis; Glomerulosclerosis, Focal Segmental
• Other Study ID Numbers: CL012_140; LUMINA-2 (Other Identifier: Chemocentryx)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No