A Study of CCX140-B in Subjects With FSGS

A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects With Focal Segmental Glomerulosclerosis (FSGS)

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

Study Overview

• Status: Completed
• Conditions: Focal Segmental Glomerulosclerosis; FSGS; Glomerulosclerosis
• Intervention / Treatment: Other: Placebo; Drug: CCX140-B; Drug: CCX140-B; Drug: CCX140-B

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 Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia
    • Royal Melbourne Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N4A6
      • St. Josephs Healthcare - Hamilton
    • Toronto, Ontario, Canada, M5G2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M4G 3E8
      • Sunnybrook Health Sciences Centre (Odette Cancer Center)
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V2H1
      • CISSS de la Montérégie-Centre - Hôpital Charles LeMoyne
• France
  • Bordeaux, France, 33076
    • CHU Bordeaux- Hospital Pellegrin
  • Créteil, France, 94010
    • CHU Henri Mondor
  • Grenoble, France, 38043
    • Chu de Grenoble
  • Grenoble cedex 9, France, 38043
    • Chu de Grenoble
  • Marseille, France, 13385
    • APHM - Hôpital de la Conception
  • Metz, France, 57045
    • Hopitaux Prives de Metz
• Italy
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni xxiii
  • Genova, Italy, 16132
    • IRCCS Azienda Ospedaliera Universitaria San Martino IST
  • Montichiari, Italy, 25018
    • Presidio Ospedaliero di Montichiari-A.O. Spedali Civili di Brescia
  • Pavia, Italy, 27100
    • Fondazione S. Maugeri IRCCS
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore
• New Zealand
  • New Plymouth, New Zealand, 4310
    • Taranaki Base Hospital
  • Auckland
    • Takapuna, Auckland, New Zealand, 0622
      • North Shore Hospital
• Poland
  • Białystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku - II Klinika Nefrologii z Oddzialem Leczenia Nadcisnienia Tetniczego i Pododdzialem Dializoterapii
  • Kraków, Poland
    • SCM Sp. Zo.o.
  • Szczecin, Poland
    • Samodzielny Publiczny Szpital Kliniczny
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny Klinika Nefrologii i Medycyny Transplantacyjnej
  • Łódź, Poland
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnez Centralny Szpital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0OQ
    • Cambridge University - Addenbrooke's Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust Manchester
  • Swansea, United Kingdom, SA6 6NL
    • Morriston Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • AKDHC
  • 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
      • MGH
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Sciences Center
  • Utah
    • Salt Lake City, Utah, United States, 84115
      • Utah Kidney Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group A; Placebo (N=10)	Other: Placebo; Three placebo tablets, taken twice daily (BID), per os, for 84 days (12 weeks); Other Names: CCX140-B Placebo
Experimental: Group B; CCX140-B 5 mg once daily (N=10)	Drug: CCX140-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.; Other Names: Group B; Drug: CCX140-B; Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.; Other Names: Group C; Drug: CCX140-B; Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.; Other Names: Group D
Experimental: Group C; CCX140-B 10 mg twice daily (N=10)	Drug: CCX140-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.; Other Names: Group B; Drug: CCX140-B; Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.; Other Names: Group C; Drug: CCX140-B; Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.; Other Names: Group D
Experimental: Group D; CCX140-B 15 mg twice daily (N=10)	Drug: CCX140-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.; Other Names: Group B; Drug: CCX140-B; Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.; Other Names: Group C; Drug: CCX140-B; Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.; Other Names: Group D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Baseline to Week 12
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.	Baseline to Week 12, and Week 12 to Week 24
Change From Baseline in Activated Partial Thromboplastin Time	Normal Range: 23.9 - 40.0	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Alanine Aminotransferase	Normal Range: 6 - 41 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
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	Normal range: 22-123 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Aspartate Aminotransferase	Normal range : 9-34 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Bicarbonate	Normal range: 21-33 mmol/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Bilirubin	Normal range: 0.1-1.10 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma C Reactive Protein	Normal range: 0.0-3.0 mg/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Calcium	Normal range: 8.5-10.5 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Chloride	Normal range: 95-110 mmol/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Cholesterol	Normal range: 100-200 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Creatine Kinase	Normal range: 23-210 U/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Creatinine	Normal range: 0.62-1.44 mg/dL	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Cystatin C	Normal range: 0.53-0.95 mg/L	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
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 Plasma HDL Cholesterol	HDL -High-density lipoprotein	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
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	LDL - Low-density lipoprotein	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
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 Eosinophils		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
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 Erythrocyte Mean Corpuscular HGB Concentration	HGB - 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 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)
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 Urine Protein		Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
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	Endpoint at Week 12 for Double-Blind Treatment Period and Endpoint at Week 24 for Open-Label Extension

Collaborators and Investigators

• Sponsor: ChemoCentryx
• Collaborators: Medpace, Inc.
• Investigators: Study Director: Peter Staehr, MD, ChemoCentryx

Publications and helpful links

General Publications

• Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2018
• Primary Completion (Actual): February 19, 2020
• Study Completion (Actual): February 19, 2020

Study Registration Dates

• First Submitted: March 28, 2018
• First Submitted That Met QC Criteria: May 23, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulosclerosis, Focal Segmental
• Other Study ID Numbers: CL011_140; LUMINA-1 (Other Identifier: Chemocentryx); NCT03536754 (Other Identifier: US NCT number); 134007 (Other Identifier: IND)

Drug and device information, study documents

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