Tolerability and Efficacy of RJX in Patients With COVID-19

NCT04708340 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: RPI015
• Study Type: interventional
• Target: 237
• Locations: 1 country
• Sites: 3

Brief Summary

This study is designed as a 2-part, 2-cohort, double-blind, randomized, placebo controlled, multicenter Phase 1/2 study to evaluate the safety, tolerability and efficacy of RJX in patients with COVID-19.

Conditions

COVID-19; Acute Respiratory Distress Syndrome; SARS-CoV-2; Hypoxemia

Outcome Measures

Primary Outcomes (3)

• Safety as measured by DLTs and drug related SAE's

  • Part 1, Cohorts 1 and 2: Cumulative incidence of DLTs and drug-related SAEs (viz., sum of DLT + SAEs) reported within 14 days of first dose of RJX (Part 1) or reported within 60 days of first dose of study drug (Part 2)

  Up to 60 days post-enrollment

• Tolerability and Efficacy measured by progression of disease through an ordinal scale.

  • Part 2, Cohort 1: Progression to severe disease on an 8-point ordinal scale from a clinical status score of 4 or 5 to a clinical status score of 3, 2, or 1 within 2 weeks of first dose of study drug

  Within 2 weeks

• Efficacy measured by time to resolution of respiratory failure

  • Part 2, Cohort 2: Time to resolution of respiratory failure (TTRRF), with status change on an 8-point ordinal scale from a clinical status score of 3 to a clinical status score of ≥4

  60-days post enrollment

Secondary Outcomes (6)

• Efficacy as measured by day of ICU care.

  60-days post enrollment

• Safety, Tolerability, Efficacy measured by mortality over 28 Days.

  28-days post enrollment

• Efficacy measured by mean change in baseline clinical status on Days 7 and 14.

  14-days post enrollment

• Efficacy measured by mean change in hospitalization days on Days 7 and 14.

  14-days post enrollment

• Efficacy measured by time to coming off supplemental oxygen on Days 7 and 14.

  14-days post enrollment

Other Outcomes (14)

• Evaluate Change in Serum CRP Concentration

  Up to 28-days post randomization

• Evaluate Change in Serum Ferritin Concentration

  Up to 28-days post randomization

• Evaluate Change in Serum D-dimer Concentration

  Up to 28-days post randomization

Study Arms (2)

Arm A: RJX

ACTIVE COMPARATOR

1. RJX 20 mL (10 mL of Vial A plus 10 mL of Vial B) mixed in normal saline, total volume 120 mL, administered by IV infusion over a period of 40 minutes +/- 10 minutes once daily. 2. Standard of care (current antiviral and/or supportive care treatment currently in place at the institution for COVID-19 treatment). 3. Patients in Part 1 are allowed to receive only one 7-day cycle of RJX while patients in Part 2 may be treated daily for up to 14 days.

Drug: Rejuveinix (RJX) Active Comparator

Arm B: Placebo

PLACEBO COMPARATOR

1. Placebo (total of 20 mL normal saline) mixed in normal saline IV, total volume 120 mL of normal saline IV, administered by IV infusion over a period of 40 minutes +/- 10 minutes once daily. 2. Standard of care (current antiviral and/or supportive care treatment currently in place at the institution for COVID-19 treatment). 3. Patients in Part 1 will not receive placebo. 4. Patients in Part 2 may be treated daily for up to 14 days.

Drug: Placebo Comparator

Interventions

Rejuveinix (RJX) Active Comparator DRUG

Active drug comprised of: ascorbic acid, magnesium sulfate heptahydrate, cyanocobalamin, thiamine, riboflavin 5' phosphate, niacinamide, pyridoxine, calcium d-pantothenate, and sodium bicarbonate.

Also known as: RJX, Rejuveinix

Arm A: RJX

Placebo Comparator DRUG

0.9% Sodium Chloride in Water for Injection a.k.a. Normal Saline for injection

Also known as: 0.9% Sodium Chloride in Water for Injection, USP., Normal Saline for Injection, USP

Arm B: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1 (Part 1 and Part 2):
• Hospitalized COVID-19 patients ≥18 years without hypoxemia who are either not receiving any oxygen therapy OR are receiving supplemental oxygen via mask or nasal prongs (namely, clinical status score 4 or 5 on an 8-point ordinal scale)
• Hospitalized COVID-19 patients age ≥65 years AND type 2 diabetes or hypertension, OR
• Hospitalized COVID-19 patients ≥18 years AND abnormal blood tests with CRP \>50 mg/L PLUS at least 1 of the following biomarkers:
• D-dimer \>1,000 ng/mL
• Ferritin \>500 µg/L
• High sensitivity cardiac troponin \>2 × ULN
• LDH \>245 U/L
• Cohort 2 (Part 1 and Part 2):
• Hospitalized COVID-19 patients with hypoxemia who are either receiving NIPPV OR high-flow oxygen (namely, clinical status score 3 on an 8-point ordinal scale).
• Bilateral opacities on a chest x-ray OR chest CT scan. Cohort 1 and Cohort 2 (Parts 1 and 2)
• Male and non-pregnant, non-lactating female patients with SARS-CoV-2 infection that is documented by a Food and Drug Administration (FDA)-authorized diagnostic reverse transcription polymerase chain reaction test at/or within 4 days of Screening
• ≥18 years of age
• Body weight ≥40 kg at Screening
• History of COVID-19 within the last 2 weeks prior to study enrollment

You may not qualify if:

• Receiving high-flow oxygen OR NIPPV. Cohort 1 and Cohort 2
• ARDS by Berlin definition (Appendix 16.2)
• On extracorporeal membrane oxygenation
• Uncontrolled hypertension (systolic blood pressure \[BP\] \>150 mmHg and/or diastolic BP \>100 mmHg), unstable angina, congestive heart failure of New York Heart Association Classification Class III or IV (i.e., Class III: marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g., walking short distances \[20 100 m\], comfortable only at rest; Class IV: severe limitations, experiences symptoms even while at rest, mostly bedbound patients), serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 12 months prior to enrollment
• Subjects with a history of congenital long QT syndrome or of Torsades de pointes; subjects with bradycardia (\<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only); subjects with any of the following findings on electrocardiogram (ECG): QTc interval \>470 msec in women OR \>450 msec in men; subjects requiring any drugs known to prolong the QTc interval, including antiarrhythmic medications
• Shock or hypotension requiring vasoactive peptides, such as dopamine, norepinephrine, epinephrine, or dobutamine
• Renal function impairment with creatinine ≥2 mg/dL
• Liver function impairment with total bilirubin ≥2 mg/dL
• Platelet count \<50,000/µL
• Multi-organ failure
• History of an allergic reaction or hypersensitivity to the study drug or any component of the study drug formulation
• Use of systemic corticosteroids, nonsteroidal anti-inflammatory drugs, antibiotics, and antiviral drugs that are not part of the standard of care
• Presence of any uncontrolled concomitant illness (e.g., bacterial sepsis or invasive fungal infection), or other serious illness and medical conditions, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with their participation in the study
• Pregnancy or breast-feeding (for women)

Sponsors & Collaborators

• Reven Pharmaceuticals, Inc.: lead

Study Sites (3)

Memorial Hermann Memorial City Medical Center

Houston, Texas, 77024, United States

Location

Memorial Hermann Southeast Hospital

Houston, Texas, 77089, United States

Location

Christus Santa Rosa Hospital

New Braunfels, Texas, 78130, United States

Location

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome; Hypoxia

Interventions

ascorbic acid, magnesium sulfate heptahydrate, cyanocobalamin, thiamine hydrochloride, riboflavin 5' phosphate, niacinamide, pyridoxine hydrochloride, and calcium D-pantothenate drug combination; Sodium Chloride; Water; Injections; Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Hydroxides; Alkalies; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Masking the dose administered
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Part 1, RJX will be administered daily for 7 days (1 cycle). In Part 2, Placebo or RJX will be administered daily for 7 days for 1 cycle but may receive 2 cycles. Each Cohort is comprised of Part 1, a single site, and Part 2, multiple sites. The 2 Cohorts are: Cohort 1: * Hospitalized COVID-19 patients ≥18 years without hypoxemia and either not receiving any oxygen therapy OR are receiving supplemental oxygen via mask or nasal prongs (clinical status score 4 or 5 on 8-point ordinal scale). * Patients are required to have the following high-risk characteristics * Age ≥65 years AND type 2 diabetes or hypertension OR * Age ≥18 years with abnormal blood tests AND CRP \>50 mg/L PLUS at least 1 of the following biomarkers abnormal: a. D-dimer, b. Ferritin, c. High sensitivity cardiac troponin, d. LDH Cohort 2: • Hospitalized COVID-19 patients with hypoxemia and without ARDS who are receiving either non-invasive positive pressure ventilation (NIPPV) OR high flow oxygen

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 13, 2021
• Study Start: March 25, 2021
• Primary Completion: October 1, 2022
• Study Completion: February 1, 2023
• Last Updated: March 15, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)