A Study of CCX140-B in Subjects With FSGS

Amgen46 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

FSGS Focal Segmental Glomerulosclerosis Glomerulosclerosis

Interventions

PlaceboOTHER

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

CCX140-BDRUG

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

CCX140-BDRUG

Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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). \-

Locations (37)

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: Baseline to Week 12, and Week 12 to Week 24

Change From Baseline in Activated Partial Thromboplastin Time

Normal Range: 23.9 - 40.0

Time frame: 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

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Alkaline Phosphatase

Time frame: 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

Time frame: 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

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Bicarbonate

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.

AKDHC

Phoenix, Arizona, United States

Los Angeles Biomedical Research Institute

Torrance, California, United States

Northwest Louisiana Nephrology

Shreveport, Louisiana, United States

MGH

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

East Carolina University

Greenville, North Carolina, United States

Rhode Island Hospital

Providence, Rhode Island, United States

University of Texas Health Sciences Center

Houston, Texas, United States

Utah Kidney Research Institute

Salt Lake City, Utah, United States

Monash Medical Centre

Clayton, Victoria, Australia

...and 27 more locations

Normal range: 21-33 mmol/L

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Direct Bilirubin

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Glucose

Time frame: 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

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Indirect Bilirubin

Time frame: 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

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Lactate Dehydrogenase

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Pancreatic Lipase

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Magnesium

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Phosphate

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Potassium

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Protein

Time frame: 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

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Prothrombin Time

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Sodium

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Triglycerides

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Urate

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Plasma Urea Nitrogen

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Basophils

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Basophils/Leukocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Eosinophils

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Eosinophils/Leukocytes

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Erythrocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Hematocrit

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Hemoglobin

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Leukocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Lymphocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Lymphocytes/Leukocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Monocytes/Leukocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Neutrophils

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Neutrophils/Leukocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Platelets

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Reticulocytes/Erythrocytes

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Urine Albumin

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Urine Creatinine

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Change From Baseline in Urine Protein

Time frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)

Secondary Outcomes

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

Time frame: 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

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