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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 46
- 试验地点
- 37
- 主要终点
- Change From Baseline in Plasma Bilirubin
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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. -
排除标准
- •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.
- •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).
研究组 & 干预措施
Group A
Placebo (N=10)
干预措施: Placebo (Other)
Group B
CCX140-B 5 mg once daily (N=10)
干预措施: CCX140-B (Drug)
Group C
CCX140-B 10 mg twice daily (N=10)
干预措施: CCX140-B (Drug)
Group D
CCX140-B 15 mg twice daily (N=10)
干预措施: CCX140-B (Drug)
结局指标
主要结局
Change From Baseline in Plasma Bilirubin
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Urate
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Creatinine
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Amylase
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Glucose
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma HDL Cholesterol
时间窗: 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
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Lactate Dehydrogenase
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Pancreatic Lipase
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Potassium
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Chloride
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Urea Nitrogen
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Phosphate
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Triglycerides
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Sodium
时间窗: 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
时间窗: 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
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Erythrocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Hematocrit
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Hemoglobin
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Leukocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Lymphocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Lymphocytes/Leukocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Monocytes/Leukocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Neutrophils
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Neutrophils/Leukocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Platelets
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Reticulocytes/Erythrocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Urine Albumin
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Urine Creatinine
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Urine Protein
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Plasma Protein
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Prothrombin Time
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Basophils
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Basophils/Leukocytes
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Eosinophils
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
Change From Baseline in Eosinophils/Leukocytes
时间窗: 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
时间窗: Baseline to Week 12 (double-blind treatment period) and Week 12 to Week 24 (open-label extension)
HGB - Hemoglobin
次要结局
- 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)