A Safety and Tolerability Study of RJX Drug Product in Healthy Participants

NCT03680105 | Completed Phase 1 Results FDA Drug

• 1 other identifier: RPI003
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Critical Limb Ischemia

Outcome Measures

Primary Outcomes (3)

• Treatment-related Adverse Events (TEAE) Reporting of RJX

  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).

  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.

  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

Study Arms (9)

Part 1; Cohort 1; RJX or Placebo

EXPERIMENTAL

Participants in Part 1; Cohort 1 will receive a single 0.024 mL/kg dose of RJX or matching placebo on Day 1.

Drug: RJX; Drug: Placebo

Part 1; Cohort 2; RJX or Placebo

EXPERIMENTAL

Participants in Part 1; Cohort 2 will receive a single 0.076 mL/kg dose of RJX or matching placebo on Day 1.

Drug: RJX; Drug: Placebo

Part 1; Cohort 3; RJX or Placebo

EXPERIMENTAL

Participants in Part 1; Cohort 3 will receive a single 0.240 mL/kg dose of RJX or matching placebo on Day 1.

Drug: RJX; Drug: Placebo

Part 1; Cohort 4; RJX or Placebo

EXPERIMENTAL

Participants in Part 1; Cohort 4 will receive a single 0.5 mL/kg dose of RJX or matching placebo on Day 1.

Drug: RJX; Drug: Placebo

Part 1; Cohort 5; RJX or Placebo

EXPERIMENTAL

Participants in Part 1; Cohort 5 will receive a single 0.759 mL/kg dose of RJX or matching placebo on Day 1.

Drug: RJX; Drug: Placebo

Part 1; Cohort 6; RJX or Placebo

EXPERIMENTAL

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.

Drug: RJX; Drug: Placebo

Part 2; Cohort 1; RJX or Placebo

EXPERIMENTAL

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.

Drug: RJX; Drug: Placebo

Part 2; Cohort 2; RJX or Placebo

EXPERIMENTAL

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.

Drug: RJX; Drug: Placebo

Part 2; Cohort 3; RJX or Placebo

EXPERIMENTAL

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.

Drug: RJX; Drug: Placebo

Interventions

RJX DRUG

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).

Part 1; Cohort 1; RJX or Placebo; Part 1; Cohort 2; RJX or Placebo; Part 1; Cohort 3; RJX or Placebo; Part 1; Cohort 4; RJX or Placebo; Part 1; Cohort 5; RJX or Placebo; Part 1; Cohort 6; RJX or Placebo; Part 2; Cohort 1; RJX or Placebo; Part 2; Cohort 2; RJX or Placebo; Part 2; Cohort 3; RJX or Placebo

Placebo DRUG

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.

Part 1; Cohort 1; RJX or Placebo; Part 1; Cohort 2; RJX or Placebo; Part 1; Cohort 3; RJX or Placebo; Part 1; Cohort 4; RJX or Placebo; Part 1; Cohort 5; RJX or Placebo; Part 1; Cohort 6; RJX or Placebo; Part 2; Cohort 1; RJX or Placebo; Part 2; Cohort 2; RJX or Placebo; Part 2; Cohort 3; RJX or Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Reven Pharmaceuticals, Inc.: lead
• ICON plc: collaborator
• ERT: Clinical Trial Technology Solutions: collaborator

Study Sites (1)

ICON Early Phase Services

San Antonio, Texas, 78209, United States

Location

Related Publications (3)

• 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.

  PMID: 36052743 DERIVED

• 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.

  PMID: 35721744 DERIVED

• 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.

  PMID: 33244300 DERIVED

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Results Point of Contact

• Title: Head, Global Clinical Affairs
• Organization: Reven Pharmaceuticals

kristina.cabala@reven.com

13036691336

Study Officials

• Dennis A Ruff, MD

  ICON Early Phase Services

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: September 21, 2018
• Study Start: August 24, 2018
• Primary Completion: January 15, 2019
• Study Completion: January 15, 2019
• Last Updated: April 27, 2020
• Results First Posted: April 14, 2020

Record last verified: 2020-04

Locations

US (1)