Official Title
A Two-part, Two-cohort, Double-blind, Randomized, Placebo-controlled, Multicenter Phase 1/2 Study to Evaluate the Safety, Tolerability and Efficacy of REJUVEINIX (RJX) in Patients With COVID-19
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.

Detailed Description

For each cohort, there will be an open label Safety Lead-in (Part 1) and a placebo
controlled, randomized, double-blind portion (Part 2). In Part 1, RJX will be administered
daily for 7 days. In the active treatment arm of Part 2 for both cohorts, RJX will be
administered daily for 7 days per cycle and patients may receive up to 2 cycles. As detailed
below, patients will be allowed to receive a second 7 day cycle of therapy based on the
medical judgment of the Investigator. The total RJX exposure during Part 2 could therefore be
up to 14 days. Both cohorts will start and enroll in parallel and independently. A safety
follow-up period will begin at Day 14/Discharge, or when treatment is discontinued, and will
continue for approximately 60 days post discharge. Part 1 will be conducted at a single site
and Part 2 will be conducted at multiple sites. The 2 cohorts in this study are:

- Cohort 1:

- 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).

- Patients are required to have the following high-risk characteristics

1. Age ≥65 years AND type 2 diabetes or hypertension OR

2. Age ≥18 years with abnormal blood tests AND CRP >50 mg/L PLUS at least 1 of
the following biomarkers:

1. D-dimer >1,000 ng/mL,

2. Ferritin >500 µg/L,

3. High sensitivity cardiac troponin >2 × upper limit of normal (ULN),

4. LDH >245 U/L.

- Cohort 2:

- Hospitalized COVID-19 patients with hypoxemia without ARDS who are receiving either
non-invasive positive pressure ventilation (NIPPV) OR high flow oxygen (namely,
clinical status score 3 on an 8-point ordinal scale).

Active, not recruiting
COVID-19
Acute Respiratory Distress Syndrome
SARS-CoV-2
Hypoxemia

Drug: Rejuveinix (RJX) Active Comparator

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

Drug: Placebo Comparator

0.9% Sodium Chloride in Water for Injection a.k.a. Normal Saline for injection
Other Name: Array

Eligibility Criteria

Inclusion Criteria

Cohort 1 (Part 1 and Part 2):

1. 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)

2. Hospitalized COVID-19 patients age ≥65 years AND type 2 diabetes or hypertension, OR

3. Hospitalized COVID-19 patients ≥18 years AND abnormal blood tests with CRP >50 mg/L
PLUS at least 1 of the following biomarkers:

1. D-dimer >1,000 ng/mL

2. Ferritin >500 µg/L

3. High sensitivity cardiac troponin >2 × ULN

4. LDH >245 U/L

Cohort 2 (Part 1 and Part 2):

4. 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).

5. Bilateral opacities on a chest x-ray OR chest CT scan. Cohort 1 and Cohort 2 (Parts 1
and 2)

6. 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

7. ≥18 years of age

8. Body weight ≥40 kg at Screening

9. History of COVID-19 within the last 2 weeks prior to study enrollment

10. The patient OR a legally authorized representative has provided written informed
consent

11. Females of childbearing potential must have a negative beta human chorionic
gonadotropin pregnancy test at Screening

12. Females of childbearing potential must agree to be abstinent or else use a medically
acceptable form of contraception from the Screening period through Day 28. Medically
acceptable forms of contraception including implants, injectables, combined oral
contraceptives, some intrauterine devices, sexual abstinence or vasectomy, and
double-barrier method [condom and occlusive cap (diaphragm or cervical/vault caps)]
with spermicidal foam/gel/film/suppository

Exclusion Criteria Cohort 1

1. Receiving high-flow oxygen OR NIPPV. Cohort 1 and Cohort 2

2. ARDS by Berlin definition (Appendix 16.2)

3. On extracorporeal membrane oxygenation

4. 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

5. 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

6. Shock or hypotension requiring vasoactive peptides, such as dopamine, norepinephrine,
epinephrine, or dobutamine

7. Renal function impairment with creatinine ≥2 mg/dL

8. Liver function impairment with total bilirubin ≥2 mg/dL

9. Platelet count <50,000/µL

10. Multi-organ failure

11. History of an allergic reaction or hypersensitivity to the study drug or any component
of the study drug formulation

12. Use of systemic corticosteroids, nonsteroidal anti-inflammatory drugs, antibiotics,
and antiviral drugs that are not part of the standard of care

13. 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

14. Pregnancy or breast-feeding (for women)

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
United States
Locations

Memorial Hermann Memorial City Medical Center
Houston, Texas, United States

Memorial Hermann Southeast Hospital
Houston, Texas, United States

Christus Santa Rosa Hospital
New Braunfels, Texas, United States

Fatih M Uckun, M.D., PhD
Study Director
Reven Pharmaceutical

Reven Pharmaceuticals, Inc.
NCT Number
MeSH Terms
COVID-19
Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Hypoxia
Ascorbic acid, magnesium sulfate heptahydrate, cyanocobalamin, thiamine hydrochloride, riboflavin 5' phosphate, niacinamide, pyridoxine hydrochloride, and calcium D-pantothenate drug combination