A Safety and Tolerability Study of RJX Drug Product in Healthy Participants
Condition: Critical Limb Ischemia
MeSH terms: Chronic Limb-Threatening Ischemia; Ischemia
Intervention: RJX; Placebo
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Designed as a single center, two-part, double-blind, placebo-controlled, randomized study to
      assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RJX in
      healthy participants.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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;

          2. Have a body mass index of 18 kg/m2 to 35 kg/m2, inclusive, at screening. In addition,
             weight cannot exceed 132 kg;

          3. Have negative screening assessment for viral hepatitis (hepatitis B or hepatitis C)
             and human immunodeficiency virus;

          4. Have negative routine urine drug screen and negative alcohol breath test at screening
             and Day -1;

          5. A female participant is eligible to participate if she is not pregnant,not
             breastfeeding, and at least 1 of the following conditions applies:

               1. 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);

               2. 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;

          6. 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;

          7. 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;

          8. Venous access sufficient to allow for blood sampling per the protocol;

          9. Reliable and willing to make themselves available for the duration of the study and
             are willing to follow study procedures;

         10. Given written informed consent prior to any study procedures being performed

        Exclusion Criteria:

          1. 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.

          2. 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);

          3. Have a hsCRP above 1.25 × upper limit of normal;

          4. 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;

          5. 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;

          6. 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;

          7. Have received an investigational product within the last 3 months;

          8. Have suspected allergies to RJX, related compounds, or any components of the
             formulation, or history of significant atopy;

          9. Regularly use known drugs of abuse and/or show positive findings on drug screening or
             Day -1;

         10. Are women who are pregnant, intend to become pregnant, or are lactating;

         11. 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

         12. Have donated blood of more than 500 mL within 4 weeks prior to study enrollment;

         13. 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;

         14. 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);

         15. In the opinion of the investigator or sponsor, are unsuitable for inclusion in the
             study;

         16. 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;

         17. Are Reven employees or employees of third-party organizations involved with the study
             who require exclusion of their employees.