A Study of CCX140-B in Subjects With FSGS

NCT03536754 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: CL011_140LUMINA-1NCT03536754134007
• Study Type: interventional
• Target: 46
• Locations: 8 countries
• Sites: 37

Brief Summary

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

Conditions

FSGS; Focal Segmental Glomerulosclerosis; Glomerulosclerosis

Outcome Measures

Primary Outcomes (54)

• 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 Outcomes (2)

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and 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

  Endpoint at Week 12 for Double-Blind Treatment Period and Endpoint at Week 24 for Open-Label Extension

Study Arms (4)

Group A

PLACEBO COMPARATOR

Placebo (N=10)

Other: Placebo

Group B

EXPERIMENTAL

CCX140-B 5 mg once daily (N=10)

Drug: CCX140-B

Group C

EXPERIMENTAL

CCX140-B 10 mg twice daily (N=10)

Drug: CCX140-B

Group D

EXPERIMENTAL

CCX140-B 15 mg twice daily (N=10)

Drug: CCX140-B

Interventions

Placebo OTHER

Three placebo tablets, taken twice daily (BID), per os, for 84 days (12 weeks)

Also known as: CCX140-B Placebo

Group A

CCX140-B DRUG

One 5 mg CCX140-B tablet and 2 placebo tablets in the morning; 3 placebo tablets in the evening; per os, for 84 days.

Also known as: Group B

Group B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18-75
• UPCR ≥ 1 g protein/g creatinine (or at 113 mg.mmol) at screening
• Diagnosis of FSGS based on renal biopsy or high risk genetic variant
• 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.
• Estimated glomerular filtration rate (eGFR) \>30 mL/min/1.73m2
• Clinical stable blood pressure not to exceed 145/95 mmHg
• 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.
• Immunosuppressive or immunomodulatory therapy must be stable for at least 4 weeks prior to screening and projected to remain stable through study week 12
• Glucocorticoids must be stable for at least 4 weeks prior to screening and projected to remain stable through study week 12.
• 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.
• Subjects must be willing and able to give written Informed Consent and to comply with protocol requirements.
• Subjects must be judged to be otherwise fit for the study by the Investigator. -

You may not qualify if:

• Pregnant or nursing
• History of organ transplantation
• On an organ transplant waiting list or anticipated organ transplant within 6 months of screening
• Plasmapheresis within 12 weeks of screening
• BMI ≥40
• Participation in any clinical study of an investigational product within 12 weeks or 5 half-lives of screening
• Currently on dialysis or likely to require dialysis during the blinded treatment phase of the study.
• 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.
• 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
• Renal disease associated with disorders other than FSGS that is active or has significant risk of progressing during the course of the study.
• Disorders that are associated with FSGS lesions.
• Evidence of tuberculosis.
• 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)
• Hematologic abnormalities as follows: Hb \<8 g/dL, platelets \<50,000, ANC \<1000 cells/µL) at baseline.
• QTcF greater than 450 msec.

Sponsors & Collaborators

• Amgen: lead

Study Sites (37)

AKDHC

Phoenix, Arizona, 85016, United States

Location

Los Angeles Biomedical Research Institute

Torrance, California, 90502, United States

Location

Northwest Louisiana Nephrology

Shreveport, Louisiana, 71101, United States

Location

MGH

Boston, Massachusetts, 02114, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

University of Texas Health Sciences Center

Houston, Texas, 77030, United States

Location

Utah Kidney Research Institute

Salt Lake City, Utah, 84115, United States

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Royal Melbourne Hospital

Parkville, Australia

Location

St. Josephs Healthcare - Hamilton

Hamilton, Ontario, L8N4A6, Canada

Location

Sunnybrook Health Sciences Centre (Odette Cancer Center)

Toronto, Ontario, M4G 3E8, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

Location

CISSS de la Monteregie-Centre - Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V2H1, Canada

Location

CHU Bordeaux- Hospital Pellegrin

Bordeaux, 33076, France

Location

CHU Henri Mondor

Créteil, 94010, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

APHM - Hopital de la Conception

Marseille, 13385, France

Location

Hopitaux Prives de Metz

Metz, 57045, France

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

IRCCS Azienda Ospedaliera Universitaria San Martino IST

Genova, 16132, Italy

Location

Presidio Ospedaliero di Montichiari-A.O. Spedali Civili di Brescia

Montichiari, 25018, Italy

Location

Fondazione S. Maugeri IRCCS

Pavia, 27100, Italy

Location

Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore

Rome, 00168, Italy

Location

North Shore Hospital

Takapuna, Auckland, 0622, New Zealand

Location

Taranaki Base Hospital

New Plymouth, 4310, New Zealand

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku - II Klinika Nefrologii z Oddzialem Leczenia Nadcisnienia Tetniczego i Pododdzialem Dializoterapii

Bialystok, 15-276, Poland

Location

SCM Sp. Zo.o.

Krakow, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnez Centralny Szpital

Lodz, Poland

Location

Samodzielny Publiczny Szpital Kliniczny

Szczecin, Poland

Location

Uniwersytecki Szpital Kliniczny Klinika Nefrologii i Medycyny Transplantacyjnej

Wroclaw, 50-556, Poland

Location

Cambridge University - Addenbrooke's Hospital

Cambridge, CB2 0OQ, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Salford Royal NHS Foundation Trust Manchester

Salford, M6 8HD, United Kingdom

Location

Morriston Hospital

Swansea, SA6 6NL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35224732 DERIVED

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental

Interventions

CCX140-B

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Results Point of Contact

• Title: Study Director
• Organization: ChemoCentryx

clinicaltrials@chemocentryx.com

650-210-2900

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, Phase 2

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: May 25, 2018
• Study Start: May 17, 2018
• Primary Completion: February 19, 2020
• Study Completion: February 19, 2020
• Last Updated: March 13, 2025
• Results First Posted: December 5, 2023

Record last verified: 2025-03

Locations

US (9); IT (5); FR (5); GB (4); NZ (2); PL (5); AU (3); CA (4)