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)
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- FSGS
- Sponsor
- Amgen
- Enrollment
- 46
- Locations
- 37
- Primary Endpoint
- Change From Baseline in Plasma Bilirubin
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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
- •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.
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
- •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.
Arms & Interventions
Group A
Placebo (N=10)
Intervention: Placebo
Group B
CCX140-B 5 mg once daily (N=10)
Intervention: CCX140-B
Group C
CCX140-B 10 mg twice daily (N=10)
Intervention: CCX140-B
Group D
CCX140-B 15 mg twice daily (N=10)
Intervention: CCX140-B
Outcomes
Primary Outcomes
Change From Baseline in Plasma Bilirubin
Time Frame: 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
Time Frame: 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
Time Frame: 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
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 Creatinine
Time Frame: 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 UPCR at Week 12
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Cystatin C
Time Frame: 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
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
Time Frame: 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
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 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 Chloride
Time Frame: 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
Time Frame: 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
Time Frame: 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
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 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 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 Sodium
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)
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 Time
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
Time Frame: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
HGB - Hemoglobin
Secondary Outcomes
- 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)