A Phase 1b, Randomized, Placebo-Controlled, Single-Blind, Single Ascending Dose Study in Subjects With Stage 3 or 4 Chronic Kidney Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Effect of Gemini versus placebo on the incidence of treatment-emergent adverse events.
研究概览
简要总结
Gemini is being evaluated in a placebo controlled, single dose, escalating dose study to evaluate the safety and tolerability of intravenous Gemini in adult subjects with stage 3 or 4 chronic kidney disease. Pharmacokinetics will be evaluated and measurements of the effect of Gemini on pharmacodynamic activity will be measured to assess changes in potential pharmacodynamic markers.
详细描述
Design: Randomized, Placebo Controlled, Single Blind, Single-Ascending Dose Study in Patients with Stage 3-4 CKD.
This study is planned as a placebo controlled, single dose, escalating dose study to evaluate the safety and tolerability of intravenous Gemini in adult subjects with stage 3 or 4 chronic kidney disease. This study will enroll up to 40 subjects in up to 5 cohorts. Each cohort will consist of 8 unique subjects, 6 assigned to Gemini and 2 assigned to placebo. All subjects will provide written informed consent and be screened for eligibility before enrollment. All eligibility criteria must be met prior to dosing.
On Day 1, each study subject will receive a single IV dose (each total dose volume = 20 mL) via syringe pump for at least 10 minutes but not longer than 15 minutes and as per the institution's standard method. Time 0 starts once the entire dose is administered and the line has been flushed to ensure any residual drug is delivered.
A Safety Review Committee (SRC) will assess safety and tolerability including AEs, after at least 6 subjects in each cohort have completed Day 8 to determine the subsequent cohort dose. If a grade 3 or higher adverse event is not experienced, as determined by the SRC, or the criteria for stopping dosing has not been met at a given cohort dose level, dose escalation will proceed to the next cohort and dose level.
Dosing will continue until any cohort experiences a dose limiting toxicity (DLT), defined as a dose that causes any grade 3 or higher adverse event, or stopping criteria is met or the highest dose as determined in the Phase 1 study has been tolerated. If a dose is stopped due to a DLT or stopping criteria, cohorts scheduled at a higher dose will not be utilized. The SRC will meet to review safety and tolerability data and may determine if a lower dose can be given. This dose will be documented in the minutes and a dose recommendation memo which will be provided to the clinical sites.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects ≥18 to ≤ 80 years of age at screening
- •Willing and able to provide written informed consent
- •eGFR of ≥ 15 and ≤ 60 per
- •Female subjects must be of non-childbearing potential or using a medically acceptable contraceptive regimen
- •Male subjects must be surgically sterile or using a medically acceptable contraceptive regimen
- •Willing and able to tolerate IV infusions and multiple blood draws
- •Willing to comply with the study schedule, restrictions, and requirements
排除标准
- •CKD Secondary to or associated with any of the following:
- •History of rapidly progressive glomerulonephritis (RPGN)
- •Glomerulonephritis requiring any use of immunosuppression in the last 6 months
- •Body mass index ≤ 19.0 kg/m2 or ≥ 40.0 kg/m2
- •Currently taking a sodium/glucose cotransporter-2 inhibitor (SGLT2i) or non-steroidal mineralocorticoidantagonist (MRA) requiring dose adjustments within 12 weeks prior to Day 1 or if dose is anticipated to change
- •Currently taking tumor necrosis factor (TNF) inhibitors, TNF blocker, interleukin-6 (IL-6) blockers or interleukin-1 (IL-1) blocking drugs
- •Receiving steroids or any other immunosuppressive agent or anti-inflammatory drugs
- •Currently taking an angiotensin-converting enzyme inhibitor (ACEi) and/or an angiotensin II receptor blocker (ARB) requiring dose adjustments
- •Any use of direct renin inhibitors;
- •Live vaccinations within 3 months prior to the start of the trial or expected during the trial
- •Received a mRNA vaccine within 4 weeks
- •Uncontrolled diabetes (HbA1c > 11.0%)
- •Clinical laboratory results of ALT and/or AST that are > 2.5X upper limit of normal (ULN)
- •Clinical Laboratory results of Total bilirubin that is > 1.5X the ULN
- •Has a Urine Albumin-to-Creatinine Ratio (uACR) level > 3000 mg/g
- •Age-related macular degeneration (AMD), diabetic macular edema or active diabetic proliferative retinopathy that was likely to require treatment during the trial
- •Uncontrolled hypertension
- •New York Heart Association Class IV congestive heart failure
- •Any organ transplant recipient, or a planned transplant during the study
- •Currently has known Hepatitis B or uncontrolled human immunodeficiency virus (HIV) or uncontrolled Hepatitis C virus (HCV) that may interfere with the study
- •Myocardial infarction, acute coronary syndrome, or stroke within 6 months
- •History of myelodysplastic syndrome
- •History of deep vein thrombosis (DVT) that required active treatment in the last 6 months. Superficial thrombosis is not excluded
- •History of hemosiderosis or hemochromatosis
- •History of rheumatoid arthritis or systemic lupus erythematosus (SLE)
- •History of drug use that may interfere with the study or study result
- •Red cell transfusion within 12 weeks
- •History of malignancy in the previous 5 years except for curatively resected basal cell carcinoma of skin, squamous cell carcinoma of skin or cervical carcinoma in situ
- •Coronavirus disease 2019 (COVID-19) diagnosis within 1 month
- •Evidence of active infection unless subject is appropriate for this study per the Investigator
- •Life expectancy less than 6 months
- •Intolerance to study medication
- •Pregnancy or lactation
- •Received treatment with any investigational product in any clinical study within 30 days prior to administration of study drug or five half-lives, whichever is longer
- •In the opinion of the Investigator or identified Sub-I(s), any other disease processes or confounding variables that would inappropriately alter the outcome of the study
研究组 & 干预措施
Low dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous Gemini (Drug)
Low dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous placebo (Drug)
Mid-level dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous Gemini (Drug)
Mid-level dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous placebo (Drug)
High dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous Gemini (Drug)
High dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous placebo (Drug)
Optional High dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous Gemini (Drug)
Optional High dose of intravenous Gemini infused once over 10-15 minutes.
Cohort 1, 8 subjects (6 active, 2 placebo)
干预措施: Intravenous placebo (Drug)
结局指标
主要结局
Effect of Gemini versus placebo on the incidence of treatment-emergent adverse events.
时间窗: From time of dose to Day 8
Collection of side effects reported by subjects.
Effect of Gemini vs placebo on electrical activity of the heart.
时间窗: From time of dose to Day 8
Safety measure for change in the electrical activity of the heart over a period of time using electrodes placed on the skin and recorded by electrocardiogram (ECG) after resting for at least 10 minutes in a quiet setting without distractions in a semi-supine position.
Effect of Gemini versus placebo on blood pressure.
时间窗: From time of dose to Day 8
Safety measure for change in blood pressure after 5 minutes of rest in a supine, semi-supine or sitting position.
Number of participants with abnormal laboratory hematology test results.
时间窗: From time of dose to Day 8
Clinically significant changes in blood hematology levels.
Number of participants with abnormal laboratory chemistry tests results.
时间窗: From time of dose to Day 8
Clinically significant changes in blood chemistry levels.
Number of participants with abnormal laboratory urine tests results.
时间窗: From time of dose to Day 8
Clinically significant changes in urine.
Effect of Gemini versus placebo on inflammation in the body.
时间窗: From time of dose to Day 8
Measurement of erythrocyte sedimentation rate in the blood.
Effect of Gemini versus placebo on inflammation.
时间窗: From time of dose to Day 8
Measurement of N-terminal pro b-type natriuretic peptide in the blood.
Effect of Gemini versus placebo on the inflammatory state of CKD subjects.
时间窗: From time of dose to Day 8
Measurement of highly sensitive C-reactive Protein in the blood.
Effect of Gemini versus placebo on kidney damage.
时间窗: From time of dose to Day 8
Measurement of urine albumin creatinine ratio.
Effect of Gemini versus placebo on heart rate.
时间窗: From time of dose to Day 8
Safety measure for change in heart rate (bpm) after 5 minutes of rest in a supine, semi-supine or sitting position.
Effect of Gemini versus placebo on body temperature.
时间窗: From time of dose to Day 8
Safety measure for change in body temperature (Celsius) after 5 minutes of rest in a supine, semi-supine or sitting position.
Effect of Gemini versus placebo on respiration.
时间窗: From time of dose to Day 8
Safety measure for change in respiration rate after 5 minutes of rest in a supine, semi-supine or sitting position.
Number of participants with abnormal physical exam findings.
时间窗: From time of dose to Day 8
Clinically significance changes in general appearance.
Number of participants with abnormal mental physical exam findings.
时间窗: From time of dose to Day 8
Clinically significant changes in mental status.
Number of participants with abnormal physical exam findings above the shoulders.
时间窗: From time of dose to Day 8
Clinically significant changes with HEENT (head, eyes, ears, nose, throat).
Number of participants with abnormal physical exam findings of the skin.
时间窗: From time of dose to Day 8
Clinically significant changes in the dermatologic system.
Number of participants with abnormal physical exam findings of the heart.
时间窗: From time of dose to Day 8
Clinically significant changes in the cardiovascular system.
Number of participants with abnormal physical exam findings of the lungs.
时间窗: From time of dose to Day 8
Clinically significant changes in the respiratory system.
Number of participants with abnormal physical exam findings of the digestive system.
时间窗: From time of dose to Day 8
Clinically significant changes in the gastrointestinal system.
Number of participants with abnormal physical exam findings of the body's support structure.
时间窗: From time of dose to Day 8
Clinically significant changes in the musculoskeletal system.
Number of participants with abnormal physical exam findings of the nervous system.
时间窗: From time of dose to Day 8
Clinically significant changes in the neurological system.
次要结局
- Peak observed concentration of Gemini.(From time of dose to Day 8)
- Time for Gemini to reach to maximum observed concentration.(From time of dose to Day 8)
- Total amount of Gemini that enters the systemic circulation after administration.(From time of dose to Day 8)
- Total Gemini exposure across time.(From time of dose to Day 8)
- The amount of time required for the plasma concentration of Gemini to decline by 50% .(From time of dose to Day 8)
- Volume of Gemini required to be uniformly distributed throughout the body.(From time of dose to Day 8)
- Rate which Gemini is removed from the human system.(From time of dose to Day 8)