A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Cohort Dose-Escalation Study in Patients With Chronic Kidney Disease to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of a Single Dose of COR-001 (COR-001-SC1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- The safety of a 5 mg dose of COR-001 as measured by the incidence of adverse events
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a single dose of the study drug or placebo administered subcutaneously to patients with moderate-to-severe chronic kidney disease and persistent inflammation.
详细描述
This is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a single dose of the study drug or placebo administered subcutaneously to patients with moderate-to-severe chronic kidney disease (CKD) and persistent inflammation (defined as a persistently elevated serum CRP (C-Reactive Protein) level). The primary objective is to evaluate the safety of a single dose of the study drug delivered subcutaneously. Four CKD patients will be randomized to the study drug or placebo within each dosing cohort in a ratio of 3:1. The dosing cohorts are 5 mg, 15 mg, 50 mg, and 100 mg. Each patient will be given 1 dose of the study drug and then be followed for 12 weeks for primary safety, pharmacokinetic and pharmacodynamic assessments. Next, patients will continue to be followed for an additional 20 weeks (32 weeks observation in total) for safety and anti-drug antibody assessments.
Prior to dose escalation (i.e., higher total dose than studied in the preceding cohorts), there will be a formal safety review and the data will have been determined to be acceptable by a Data Safety Monitoring Board (DSMB) which will include at least one nephrologist. The safety review required for dose escalation will include at least 21 days of treatment data from the preceding cohort(s). The DSMB will also meet to review data concerning an SAE (Serious Adverse Event) that is suspected to be study drug related
The investigative team (other than an un-blinded research pharmacist or equivalent) will be blinded to the treatment assignment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CKD stage III or IV
- •Serum CRP > 2 mg/L measured twice during the Screening period at least one week apart
- •Urine protein excretion < 3.5 g/24h estimated by a spot urine protein/creatinine ratio
- •The patient agrees to comply with the contraception and reproduction restrictions of the study - use 2 forms of acceptable contraception
排除标准
- •Patients with advanced CKD requiring chronic dialysis
- •Hospitalization over the period of 6 weeks prior to randomization
- •Use of systemic immunosuppressive drugs during the Screening Period or anticipated use of such drugs anytime during the study Note: Use of otic, ophthalmic, inhaled, and topical corticosteroids or local corticosteroid injections are not exclusionary.
- •History of or expected to undergo living related kidney transplant during the study period
- •Currently receiving or planning to receive live or inactivated vaccines
- •Clinical evidence or suspicion of active or smoldering infection (e.g., diabetic foot ulcer) or use of antibiotics during the Screening period
- •History of a positive PPD or prior diagnosis of tuberculosis
- •Evidence of HIV infection or carrier state by serology at Screening
- •Hepatitis B or C by serology (i.e. Hepatitis B Surface Antigen or Hepatitis C antibody positive) at Screening
- •AST or ALT > 2.5x ULN at Screening
- •History of liver cirrhosis or home oxygen use
- •History of gastrointestinal ulceration or active diverticulitis in the 1 year prior to Screening
- •Absolute neutrophil count < 2 x 109/L at Screening
- •Platelet count < 100 x 109/L at Screening
- •Participated in an investigational drug study within 30 days of Screening or Screening is within 5 half-lives of the investigational compound.
- •Known allergy to the study drug or any of its ingredients
- •Breastfeeding or a positive pregnancy test at Screening or Day -
- •Any condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would in the opinion of the Investigator increase the risk of the subject's participation in the study.
- •This would include but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy, anemia attributable to a primary hematologic disease (e.g., sickle cell anemia), or any unexplained blackouts.
- •Actively treated malignancy (other than non-melanoma skin cancers) during the 1 year prior to Screening. Patients receiving hormonal treatment only during this period only may be enrolled with the approval of the medical monitor.
- •Myocardial infarction during the 3 months prior to Screening or during Screening
- •Severe arthritis, lupus, inflammatory bowel disease, asthma or other disease(s) or medical condition(s) that, in the opinion of the investigator, could interfere with hs-CRP or immune function
- •Use of CYP substrates with a narrow therapeutic index (please see detailed table below).
研究组 & 干预措施
COR-001
COR-001 5, 15, 50, or 100 mg dose (depending on dose cohort assigned to patient) given by subcutaneous injection one time only
干预措施: COR-001 (Drug)
Placebo
Placebo at pH 6.0will be given in a volume to match the volume of COR-001 being given for the dose cohort by subcutaneous injection one time only
干预措施: Placebo (Drug)
结局指标
主要结局
The safety of a 5 mg dose of COR-001 as measured by the incidence of adverse events
时间窗: 1 month after the 4th patient has received study drug
To evaluate the safety of a 5 mg dose of COR-001 delivered subcutaneously
The safety of a 100 mg dose of COR-001 as measured by the incidence of adverse events
时间窗: 1 month after the 4th patient has received study drug
To evaluate the safety of a 100 mg dose of COR-001 delivered subcutaneously
The safety of a 15 mg dose of COR-001 as measured by the incidence of adverse events
时间窗: 1 month after the 4th patient has received study drug
To evaluate the safety of a 15 mg dose of COR-001 delivered subcutaneously
The safety of a 50 mg dose of COR-001 as measured by the incidence of adverse events
时间窗: 1 month after the 4th patient has received study drug
To evaluate the safety of a 50 mg dose of COR-001 delivered subcutaneously
次要结局
- The effectiveness of COR-001 as measured by levels of an inflammatory marker(Screening and at weeks 1 - 5, 8, 12, 20, and 32.)
- Pharmacokinetic analysis: terminal elimination half-life (t1/2)(Pre-dose, 4 hours post-dose, and days 2-7, 11, 15, 22, 29, 57, 85, 141, and 225 post-dose.)
- Pharmacokinetic analysis: maximum serum drug concentrations (Cmax)(Pre-dose, 4 hours post-dose, and days 2-7, 11, 15, 22, 29, 57, 85, 141, and 225 post-dose.)
- Pharmacokinetic analysis: area under the serum drug concentration-time curve (AUC)(Pre-dose, 4 hours post-dose, and days 2-7, 11, 15, 22, 29, 57, 85, 141, and 225 post-dose.)