Clinical trial NCT03536754: A Study of CCX140-B in Subjects With FSGS
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: FSGS
Focal Segmental Glomerulosclerosis
Glomerulosclerosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-05-25
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Randomized, placebo-controlled, Phase 2
Primary purpose: TREATMENT

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.

Eligibility criteria: 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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Primary outcomes:
measure: Change From Baseline in UPCR at Week 12
timeFrame: Baseline to Week 12
measure: Number of Participants of Treatment-emergent AEs (TEAE), TEAEs Leading to Study Withdrawal, and Serious Adverse Events (SAEs)
timeFrame: Baseline to Week 12, and Week 12 to Week 24
measure: Change From Baseline in Activated Partial Thromboplastin Time
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Alanine Aminotransferase
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Alkaline Phosphatase
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Amylase
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Aspartate Aminotransferase
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Bicarbonate
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Bilirubin
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma C Reactive Protein
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Calcium
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Chloride
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Cholesterol
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Creatine Kinase
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Creatinine
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Cystatin C
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Direct Bilirubin
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Glucose
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma HDL Cholesterol
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Indirect Bilirubin
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma LDL Cholesterol
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Lactate Dehydrogenase
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Pancreatic Lipase
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Magnesium
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Phosphate
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Potassium
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Protein
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Prothrombin Intl. Normalised Ratio
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Prothrombin Time
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Sodium
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Triglycerides
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Urate
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Plasma Urea Nitrogen
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Basophils
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Basophils/Leukocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Eosinophils
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Eosinophils/Leukocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Erythrocyte Mean Corpuscular Volume
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Erythrocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Hematocrit
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Hemoglobin
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Leukocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Lymphocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Lymphocytes/Leukocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Monocytes/Leukocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Neutrophils
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Neutrophils/Leukocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Platelets
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Reticulocytes/Erythrocytes
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Urine Albumin
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Urine Creatinine
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Change From Baseline in Urine Protein
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Secondary outcomes:
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12 and Week 24
timeFrame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
measure: Proportion of Subjects Achieving Complete or Partial Renal Remission at Week 12 and Week 24
timeFrame: Endpoint at Week 12 for Double-Blind Treatment Period and Endpoint at Week 24 for Open-Label Extension
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: AKDHC
state: Arizona
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute
state: California
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Boston
country: United States
facility: MGH
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Houston
country: United States
facility: University of Texas Health Sciences Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Kidney Research Institute
state: Utah
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Hamilton
country: Canada
facility: St. Josephs Healthcare - Hamilton
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre (Odette Cancer Center)
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: CISSS de la Monteregie-Centre - Hopital Charles LeMoyne
state: Quebec
city: Bordeaux
country: France
facility: CHU Bordeaux- Hospital Pellegrin
city: Créteil
country: France
facility: CHU Henri Mondor
city: Grenoble cedex 9
country: France
facility: CHU de Grenoble
city: Grenoble
country: France
facility: CHU de Grenoble
city: Marseille
country: France
facility: APHM - Hopital de la Conception
city: Metz
country: France
facility: Hopitaux Prives de Metz
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Genova
country: Italy
facility: IRCCS Azienda Ospedaliera Universitaria San Martino IST
city: Montichiari
country: Italy
facility: Presidio Ospedaliero di Montichiari-A.O. Spedali Civili di Brescia
city: Pavia
country: Italy
facility: Fondazione S. Maugeri IRCCS
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore
city: Takapuna
country: New Zealand
facility: North Shore Hospital
state: Auckland
city: New Plymouth
country: New Zealand
facility: Taranaki Base Hospital
city: Białystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku - II Klinika Nefrologii z Oddzialem Leczenia Nadcisnienia Tetniczego i Pododdzialem Dializoterapii
city: Kraków
country: Poland
facility: SCM Sp. Zo.o.
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny Klinika Nefrologii i Medycyny Transplantacyjnej
city: Łódź
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnez Centralny Szpital
city: Cambridge
country: United Kingdom
facility: Cambridge University - Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust Manchester
city: Swansea
country: United Kingdom
facility: Morriston Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.