A Study of CCX140-B in Subjects With FSGS

Phase 2

Completed

Conditions: Glomerulosclerosis
FSGS
Focal Segmental Glomerulosclerosis

Interventions: Other: Placebo
Drug: CCX140-B

Registration Number: NCT03536754

Lead Sponsor: Amgen

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

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

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. -

Exclusion Criteria

Pregnant or nursing
History of organ transplantation
On an organ transplant waiting list or anticipated organ transplant within 6 months of screening
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
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.
History of alcohol or illicit drug abuse or of lithium, pamidronate and interferon. Recreational use of cannabis is not excluded where legal.
History of gastrointestinal conditions that may interfere with study medication compliance.
Known hypersensitivity to CCX140-B or inactive ingredients of the CCX140-B tablets (including microcrystalline cellulose, starch, crospovidone, magnesium stearate, or silicon dioxide).
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.
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.
Subjects taking strong CYP3A4 inducers or strong CYP3A4 inhibitors within two weeks prior to screening.
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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group A	Placebo	Placebo (N=10)
Group B	CCX140-B	CCX140-B 5 mg once daily (N=10)
Group C	CCX140-B	CCX140-B 10 mg twice daily (N=10)
Group D	CCX140-B	CCX140-B 15 mg twice daily (N=10)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Plasma Bilirubin	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 0.1-1.10 mg/dL
Change From Baseline in Plasma C Reactive Protein	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 0.0-3.0 mg/L
Change From Baseline in Plasma Cholesterol	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 100-200 mg/dL
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 Plasma Urate	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in UPCR at Week 12	Baseline to 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
Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs)	Baseline to Week 12, and Week 12 to Week 24	TEAEs leading to study withdrawal means study drug discontinuation in this endpoint.
Change From Baseline in Activated Partial Thromboplastin Time	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal Range: 23.9 - 40.0
Change From Baseline in Plasma Alanine Aminotransferase	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal Range: 6 - 41 U/L
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	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 22-123 U/L
Change From Baseline in Plasma Aspartate Aminotransferase	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range : 9-34 U/L
Change From Baseline in Plasma Bicarbonate	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 21-33 mmol/L
Change From Baseline in Plasma Calcium	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 8.5-10.5 mg/dL
Change From Baseline in Plasma Creatinine	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 0.62-1.44 mg/dL
Change From Baseline in Plasma Cystatin C	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 0.53-0.95 mg/L
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	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	HDL -High-density lipoprotein
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 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 Chloride	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 95-110 mmol/L
Change From Baseline in Plasma Creatine Kinase	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	Normal range: 23-210 U/L
Change From Baseline in Plasma LDL Cholesterol	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	LDL - Low-density lipoprotein
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 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 Urea Nitrogen	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)
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 Time	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	Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)	HGB - Hemoglobin

Secondary Outcome Measures

Name	Time	Method
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)	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
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	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

Trial Locations

Locations (37): Los Angeles Biomedical Research Institute
🇺🇸
Torrance, California, United States
Sunnybrook Health Sciences Centre (Odette Cancer Center)
🇨🇦
Toronto, Ontario, Canada
MGH
🇺🇸
Boston, Massachusetts, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
CHU de Grenoble
🇫🇷
Grenoble, France
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
🇮🇹
Bergamo, Italy
Cambridge University - Addenbrooke's Hospital
🇬🇧
Cambridge, United Kingdom
CHU Bordeaux- Hospital Pellegrin
🇫🇷
Bordeaux, France
University of Texas Health Sciences Center
🇺🇸
Houston, Texas, United States
AKDHC
🇺🇸
Phoenix, Arizona, United States
Presidio Ospedaliero di Montichiari-A.O. Spedali Civili di Brescia
🇮🇹
Montichiari, Italy
Samodzielny Publiczny Zaklad Opieki Zdrowotnez Centralny Szpital
🇵🇱
Łódź, Poland
Fondazione S. Maugeri IRCCS
🇮🇹
Pavia, Italy
CISSS de la Monteregie-Centre - Hopital Charles LeMoyne
🇨🇦
Greenfield Park, Quebec, Canada
Taranaki Base Hospital
🇳🇿
New Plymouth, New Zealand
North Shore Hospital
🇳🇿
Takapuna, Auckland, New Zealand
University Hospital of Wales
🇬🇧
Cardiff, United Kingdom
Samodzielny Publiczny Szpital Kliniczny
🇵🇱
Szczecin, Poland
Uniwersytecki Szpital Kliniczny Klinika Nefrologii i Medycyny Transplantacyjnej
🇵🇱
Wrocław, Poland
Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore
🇮🇹
Rome, Italy
East Carolina University
🇺🇸
Greenville, North Carolina, United States
Toronto General Hospital
🇨🇦
Toronto, Ontario, Canada
CHU Henri Mondor
🇫🇷
Créteil, France
Northwest Louisiana Nephrology
🇺🇸
Shreveport, Louisiana, United States
Austin Health
🇦🇺
Heidelberg, Victoria, Australia
Royal Melbourne Hospital
🇦🇺
Parkville, Australia
Utah Kidney Research Institute
🇺🇸
Salt Lake City, Utah, United States
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
St. Josephs Healthcare - Hamilton
🇨🇦
Hamilton, Ontario, Canada
Hopitaux Prives de Metz
🇫🇷
Metz, France
APHM - Hopital de la Conception
🇫🇷
Marseille, France
IRCCS Azienda Ospedaliera Universitaria San Martino IST
🇮🇹
Genova, Italy
SCM Sp. Zo.o.
🇵🇱
Kraków, Poland
Salford Royal NHS Foundation Trust Manchester
🇬🇧
Salford, United Kingdom
Morriston Hospital
🇬🇧
Swansea, United Kingdom
Uniwersytecki Szpital Kliniczny w Bialymstoku - II Klinika Nefrologii z Oddzialem Leczenia Nadcisnienia Tetniczego i Pododdzialem Dializoterapii
🇵🇱
Białystok, Poland
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States