A Safety and Tolerability Study of RJX Drug Product in Healthy Participants
A Phase 1, Double-blind, Placebo-controlled, Randomized, Two-Part, Ascending Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Rejuveinix (RJX) in Healthy Participants
研究概览
详细说明
Part 1 is designed as a Single Ascending Dose (SAD) escalation study with 6 cohorts. Participants will undertake a screening visit between Day -21 and Day -1 to determine eligibility in the study. Those participants that meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1). Participants will receive a single dose of investigational product via IV infusion on Day 1. The first cohort will include the initial dosing of a sentinel group. The remaining participants in Cohort 1 will be dosed if, in the opinion of the investigator or delegate, there are no significant safety concerns identified in the sentinel participants within the first 24 hours after administration of the dose. Participants will be confined to the study site from Day -1 to Day 2 (24 hours post dose) and then required to return to the study site on Day 5 for a final follow up visit. Safety and PK assessments will be performed at selected time points throughout the study.
Part 2 is designed as a Multiple Ascending Dose (MAD) escalation study with 3 cohorts. The MAD arm of the study will commence in parallel with Cohort 6 of Part 1 following completion and review of safety and PK findings for Cohorts 1, 2, 3, 4, and 5 in Part 1. Participants will undertake a screening visit between Day -21 and Day -1 to determine eligibility in the study. Those participants that meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1). Participants will be randomly assigned to receive 1 of 3 proposed doses of investigational product via IV infusion every day for 7 days.Participants will be confined to the study site from Day -1 to Day 8 (24 hours post the final dose on Day 7) and then return to the study site on Day 12 for a final follow up visit. Safety and PK assessments will be performed at selected time points throughout the study.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
Texas
-
San Antonio、Texas、美国、78209
- ICON Early Phase Services
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Healthy male and female participants aged 18 to 50 years inclusive (Cohort 1 to Cohort 5) or 51 to 70 years inclusive (Cohort 6 only),at the time of screening;
- Have a body mass index of 18 kg/m2 to 35 kg/m2, inclusive, at screening. In addition, weight cannot exceed 132 kg;
- Have negative screening assessment for viral hepatitis (hepatitis B or hepatitis C) and human immunodeficiency virus;
- Have negative routine urine drug screen and negative alcohol breath test at screening and Day -1;
A female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least 1 of the following conditions applies:
- Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy, tubal ligation or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient);
- Of childbearing potential and agrees to use 2 highly effective methods of contraception consistently during the treatment period and for at least 60 days after the last dose of investigational product;
- A male participant with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during the treatment period and for at least 60 days after the last dose of investigational product and refrains from donating sperm during this period;
- Clinical laboratory test results within normal reference range for the population or investigator site, or any results that are judged to be not clinically significant by the investigator;
- Venous access sufficient to allow for blood sampling per the protocol;
- Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures;
- Given written informed consent prior to any study procedures being performed
Exclusion Criteria:
- Have a history of clinically relevant cardiovascular disease, cancer, respiratory, hepatic, renal, gastrointestinal, endocrine (diabetes), hematological, or neurological disorders. Cohort 6 only - elderly participants with well controlled hypercholesterolemia on a stable dose of statin therapy or well controlled hypertension on a stable dose of antihypertensive medication(s), excluding diuretics, are allowed in Cohort 6 per the clinical judgment of the investigator.
- Have impaired renal function (defined as estimated glomerular filtration rate <90 cc/min/1.73m2 Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) creatinine equation at screening);
- Have a hsCRP above 1.25 × upper limit of normal;
- Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) or prolongation of corrected QT interval by Fredericia (QTcF) >440 ms in males and >450 ms in females;
- Have a supine systolic blood pressure (BP) greater than 140 mm Hg or a diastolic BP greater than 90 mm Hg. Up to 2 additional measurements may be undertaken after an appropriate resting interval at screening to confirm eligibility;
- Are currently enrolled in a clinical trial involving an investigational product, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study;
- Have received an investigational product within the last 3 months;
- Have suspected allergies to RJX, related compounds, or any components of the formulation, or history of significant atopy;
- Regularly use known drugs of abuse and/or show positive findings on drug screening or Day -1;
- Are women who are pregnant, intend to become pregnant, or are lactating;
Participants will be excluded for using any of the following medication:
- aspirin, multivitamins/vitamins or mineral preparations within 14 days prior to investigational product administration or 24 hours post the last infusion;
prescription, herbal or over the counter medications within 14 days of investigational product administration, with the exception of:
- simple analgesics such as paracetamol, excluding aspirin
- oral non-steroidal anti-inflammatory drugs
- thyroid treatment, estrogen replacement therapy
- hormonal contraception
- Statins and anti-hypertensives are permitted for elderly participants in Cohort 6 (Part 1) - see inclusion criteria #1
- Have donated blood of more than 500 mL within 4 weeks prior to study enrollment;
- Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females) or are unwilling to stop alcohol consumption for 24 hours prior to study site admission (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits). Participants must have a of negative alcohol breath test at Day -1 and no evidence of alcohol abuse in the previous 12 months, defined as > 21 weekly units for males up to age 65 and > 14 weekly units for males over 65 and females;
- Have smoked cigarettes in the last 90 days (including occasional smokers who have smoked more than 5 cigarettes per month within the last 90 days);
- In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study;
- Are investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted;
- Are Reven employees or employees of third-party organizations involved with the study who require exclusion of their employees.
学习计划
研究是如何设计的?
设计细节
- 主要用途:基础科学
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:Part 1; Cohort 1; RJX or Placebo
Participants in Part 1; Cohort 1 will receive a single 0.024 mL/kg dose of RJX or matching placebo on Day 1.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 1; Cohort 2; RJX or Placebo
Participants in Part 1; Cohort 2 will receive a single 0.076 mL/kg dose of RJX or matching placebo on Day 1.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 1; Cohort 3; RJX or Placebo
Participants in Part 1; Cohort 3 will receive a single 0.240 mL/kg dose of RJX or matching placebo on Day 1.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 1; Cohort 4; RJX or Placebo
Participants in Part 1; Cohort 4 will receive a single 0.5 mL/kg dose of RJX or matching placebo on Day 1.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 1; Cohort 5; RJX or Placebo
Participants in Part 1; Cohort 5 will receive a single 0.759 mL/kg dose of RJX or matching placebo on Day 1.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 1; Cohort 6; RJX or Placebo
Participants in Part 1; Cohort 6 will receive a single dose of RJX or matching placebo, to be determined following review of safety and PK data from Cohorts 1 to 5, on Day 1.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 2; Cohort 1; RJX or Placebo
Participants in Part 2; Cohort 1 will receive a dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days. The Part 2; Cohort 1 dose will be 1 log down from the maximum tolerated dose determined in Part 1 or at a dose determined to be safe and well tolerated in Part 1 with an acceptable PK profile. |
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 2; Cohort 2; RJX or Placebo
Participants in Part 2; Cohort 2 will receive an escalated dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
实验性的:Part 2; Cohort 3; RJX or Placebo
Participants in Part 2; Cohort 3 will receive an escalated dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.
|
RJX is an IV infusion formulation.
The appropriate RJX dose is calculated based on mL/kg.
The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained.
Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline.
To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Treatment-related Adverse Events (TEAE) Reporting of RJX
大体时间:Up to Day 5 for Part 1 and Up to Day 12 for Part 2
|
Number of participants with indicated AEs receiving RJX as assessed by CTCAE v4 03
|
Up to Day 5 for Part 1 and Up to Day 12 for Part 2
|
Safety and Tolerability of RJX as Assessed by Electrocardiograms (ECGs).
大体时间:Up to Day 2 for Part 1 and Up to Day 8 for Part 2
|
Number of participants with abnormal and clinically significant findings based on ECG.
|
Up to Day 2 for Part 1 and Up to Day 8 for Part 2
|
Safety and Tolerability of RJX as Assessed by Neurological Examinations.
大体时间:Up to Day 5 for Part 1 and Up to Day 12 for Part 2
|
Number of participants with clinically significant values and actual changes from baseline of continuous neurological assessments.
|
Up to Day 5 for Part 1 and Up to Day 12 for Part 2
|
合作者和调查者
调查人员
- 首席研究员:Dennis A Ruff, MD、ICON Early Phase Services
出版物和有用的链接
一般刊物
- Uckun FM, Saeed M, Awili M, Ozercan IH, Qazi S, Lee C, Shibli A, Skolnick AW, Prusmack A, Varon J, Barrera CI, Orhan C, Volk M, Sahin K. Evaluation of the potential of Rejuveinix plus dexamethasone against sepsis. Future Microbiol. 2022 Oct;17:1217-1229. doi: 10.2217/fmb-2022-0044. Epub 2022 Sep 2.
- Uckun FM, Orhan C, Tuzcu M, Durmus AS, Ozercan IH, Volk M, Sahin K. RJX Improves Wound Healing in Diabetic Rats. Front Endocrinol (Lausanne). 2022 Jun 2;13:874291. doi: 10.3389/fendo.2022.874291. eCollection 2022.
- Uckun FM, Carlson J, Orhan C, Powell J, Pizzimenti NM, van Wyk H, Ozercan IH, Volk M, Sahin K. Rejuveinix Shows a Favorable Clinical Safety Profile in Human Subjects and Exhibits Potent Preclinical Protective Activity in the Lipopolysaccharide-Galactosamine Mouse Model of Acute Respiratory Distress Syndrome and Multi-Organ Failure. Front Pharmacol. 2020 Nov 10;11:594321. doi: 10.3389/fphar.2020.594321. eCollection 2020.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
RJX的临床试验
-
Reven Pharmaceuticals, Inc.主动,不招人