Tolerability and Efficacy of RJX in Patients With COVID-19

Phase 1

• Conditions: COVID-19; Acute Respiratory Distress Syndrome; SARS-CoV-2; Hypoxemia
• Interventions: Drug: Rejuveinix (RJX) Active Comparator; Drug: Placebo Comparator

• Registration Number: NCT04708340
• Lead Sponsor: Reven Pharmaceuticals, Inc.

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).

Study Timeline

• Study First Submitted: 2021-01-04
• Study First Submitted QC: 2021-01-12
• Study First Posted: 2021-01-13
• Study Start: 2021-03-25
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-14
• Last Update Posted: 2022-03-15
• Primary Completion: 2022-10
• Study Completion: 2023-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 237

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: RJX	Rejuveinix (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.
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.

Primary Outcome Measures

Name	Time	Method
Tolerability and Efficacy measured by progression of disease through an ordinal scale.	Within 2 weeks	• 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
Safety as measured by DLTs and drug related SAE's	Up to 60 days post-enrollment	• 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)
Efficacy measured by time to resolution of respiratory failure	60-days post enrollment	• 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

Secondary Outcome Measures

Name	Time	Method
Efficacy measured by mean change in baseline clinical status on Days 7 and 14.	14-days post enrollment	Additional secondary endpoint for Parts 1 and 2, Cohorts 1 and 2 are: • Mean change from baseline of clinical status using an 8-point ordinal scale (with 8 being "Not hospitalized, no limitations on activities", and 1 being "Death") at Days 7 and 14
Efficacy as measured by day of ICU care.	60-days post enrollment	The key secondary endpoints for Parts 1 and 2, Cohorts 1 and 2 are: • Mean number of days of ICU care
Efficacy measured by time to coming off supplemental oxygen on Days 7 and 14.	14-days post enrollment	Additional secondary endpoint for Parts 1 and 2, Cohorts 1 and 2 are: • Time to coming off supplemental oxygen (defined as a score of ≥5 on an 8-point ordinal scale; Cohort 1 only)
Safety, Tolerability, Efficacy measured by mortality over 28 Days.	28-days post enrollment	The key secondary endpoints for Parts 1 and 2, Cohorts 1 and 2 are: • Proportion of patients that die (any cause) by Day 28 post randomization (patient may be inpatient or outpatient in follow up)
Safety and Efficacy measured by time from first dose to renal therapy.	60-days post enrollment	Additional secondary endpoint for Cohort 2, Part 2 is: • Time to initiation of renal replacement therapy
Efficacy measured by mean change in hospitalization days on Days 7 and 14.	14-days post enrollment	Additional secondary endpoint for Parts 1 and 2, Cohorts 1 and 2 are: • Mean number of hospitalization days

Trial Locations

Locations (3)

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