A Study to Evaluate the Effect of RBT-9 on Progression of COVID-19 in High-Risk Individuals (The PREVENT Study)

A Phase 2, Randomized, Placebo-Controlled Study to Evaluate the Effect of RBT-9 on Progression of COVID-19 in High-Risk Individuals (The PREVENT Study)

The overall objective is to evaluate the efficacy, tolerability, and safety of a single dose of RBT-9 versus placebo in coronavirus disease 2019 (COVID-19) infection in non-critically ill adults who are at high risk of progression.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: RBT-9 (90 mg); Drug: 0.9% sodium chloride (normal saline)

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • New Smyrna Beach, Florida, United States, 32168
      • New Smyrna Beach, FL
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Berkley, MI
  • Texas
    • El Paso, Texas, United States, 79935
      • El Paso, TX
    • Fort Worth, Texas, United States, 76104
      • Fort Worth, TX
    • Houston, Texas, United States, 77030
      • Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, ≥18 years of age at Screening.
2. Confirmed infection with SARS-CoV-2.

3. High risk of COVID-19 disease progression, defined as:

   1. 18-69 years of age with lymphopenia AND 1 additional risk factor (described below)
   2. 18-69 years of age without lymphopenia AND 2 risk factors (described below)
   3. ≥70 years of age with lymphopenia OR 1 other risk factor (described below)

   Risk Factors:

   • Documented history of coronary artery disease
   • Heart failure (New York Heart Association Class 3 or 4)
   • Chronic lung disease (eg, asthma or chronic obstructive pulmonary disease) requiring treatment
   • Documented history of stroke
   • Diabetes mellitus, requiring at least 1 prescription medicine for management
   • Documented chronic kidney disease with an estimated glomerular filtration rate <30 mL/min, not on dialysis
   • Obesity (Class 2 or 3; body mass index >34.9 kg/m2)
   • On immunosuppressive therapy
   • Oxygen saturation between 90 and 95% with or without supplemental oxygen
4. Admitted to a hospital for observation and/or treatment (controlled facility may include an emergency room, urgent care facility, temporary/modular hospital, infusion center, clinical research unit, etc).
5. If female, must be postmenopausal, surgically sterile, or if of childbearing potential, must be practicing 2 effective methods of birth control during the study and through 30 days after completion of the study.
6. For females of childbearing potential, a urine pregnancy test must be negative at the Screening Visit.
7. If male, must be surgically sterile or willing to practice 2 effective methods of birth control during the study and through 30 days after completion of the study.
8. Must be willing and able to give informed consent and comply with all study procedures.

Exclusion Criteria:

1. Anticipated need for ICU care and/or ventilatory support (invasive or noninvasive) within 24 hours.
2. Evidence of acute cardiac injury, as determined by the Investigator at the time of Screening. This may be based upon clinical signs and symptoms, ECG findings, or elevated troponin I levels.
3. Evidence of acute kidney injury not due to pre-renal azotemia or urinary tract obstruction at the time of Screening.
4. Oxygen saturation <90% on supplemental oxygen with a nasal cannula, including high-flow oxygen at the time of Screening.
5. Requires non-invasive ventilation at the time of Screening.
6. Requires dialysis at the time of Screening.
7. Has received or is receiving anti-IL-6 therapies (eg, Tocilizumab, Sarilumab, Siltuximab, etc) for the treatment of COVID-19; subjects receiving anti-IL-6 therapies for underlying medical conditions unrelated to COVID-19 are not excluded from eligibility.
8. Pregnant or lactating.
9. History of photosensitivity or active skin disease that, in the opinion of the Investigator, could be worsened by RBT-9.
10. Known hypersensitivity or previous anaphylaxis to RBT-9 (stannous protoporphyrin) or any tin-based product.
11. Treatment with an investigational drug or participation in an interventional trial within 30 days prior to the first dose of study drug.
12. Inability to comply with the requirements of the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RBT-9 (90 mg); RBT-9 (90mg) will be administered intravenously over a 120-minute period on Day 1.	Drug: RBT-9 (90 mg); Subjects will receive a single dose and study duration will be approximately 60 days per subject.
Placebo Comparator: Placebo; 0.9% sodium chloride (normal saline) will be administered intravenously over a 120-minute period on Day 1.	Drug: 0.9% sodium chloride (normal saline); Subjects will receive a single dose and study duration will be approximately 60 days per subject.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Effect of RBT-9 Versus Placebo on Clinical Status of COVID-19 Patients as Measured Using the 8-point World Health Organization (WHO) Ordinal Clinical Scale	Determining severity of COVID-19 in patients measured using the 8-point World Health Organization (WHO) Ordinal Clinical Scale which measures the clinical status of a subject at the first assessment of a given day with category 1, most favorable, and category 8, least favorable (1. Ambulatory, no limitation of activities; 2. Ambulatory, limitation of activities; 3. Hospitalized, no oxygen therapy; 4. Hospitalized, oxygen by mask or nasal prongs; 5. Hospitalized, non-invasive ventilation or high-flow oxygen; 6. Hospitalized, intubation and mechanical ventilation; 7. Hospitalized, ventilation plus additional organ support - pressors, renal replacement therapy [RRT], extracorporeal membrane oxygenation [ECMO]; 8. Death)	baseline and 7 days, baseline and 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first occurrence of death from any cause or new/worsened organ dysfunction	Time to first occurrence of either death from any cause or new/worsened organ dysfunction through Day 28, defined as at least one of the following: 1. Respiratory decompensation; 2. New or worsening congestive heart failure; 3. Requirement of vasopressor therapy and/or inotropic or mechanical circulatory support; 4. Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest; 5. Initiation of renal replacement therapy	28 Days
All-cause survival	Percentage of subjects who are alive at Day 28	28 Days
Oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio	Among subjects who begin oxygen therapy, mean change from initiation to last day on oxygen or Day 28 (whichever happens first) in SpO2/FiO2 ratio	28 Days
Fever incidence	Percentage of subjects with fever through Day 28	28 Days
Acute kidney injury (AKI) incidence	Percentage of subjects who develop AKI (defined as an increase in serum creatinine by 0.5 mg/dL or more within 48 hours or an increase in serum creatinine to 1.5 × Baseline or more within the last 7 days) through Day 28	28 Days
New or worsening congestive heart failure (HF)	Percentage of subjects with new or worsening congestive HF through Day 28	28 Days
Hospitalization status	Percentage of subjects who remain hospitalized at Day 28	28 Days
Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest	Percentage of subjects with ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest through Day 28	28 Days
Oxygen-free days	Number of oxygen-free days through Day 28	28 Days
Intensive care unit (ICU) status	Percentage of subjects transferred to the ICU through Day 28	28 Days
Days on ventilator	Number of days on mechanical ventilation through Day 28	28 Days
Time to and duration of vasopressor or inotrope utilization	Time to and duration of vasopressor or inotrope utilization through Day 28	28 Days
Dialysis status	Percentage of subjects who begin dialysis through Day 28	28 Days

Collaborators and Investigators

• Sponsor: Renibus Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2020
• Primary Completion (Actual): September 2, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: REN-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No