COVID-19
Conditions
Brief summary
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.
Interventions
DRUGRBT-9 (90 mg)
Subjects will receive a single dose and study duration will be approximately 60 days per subject.
Subjects will receive a single dose and study duration will be approximately 60 days per subject.
Sponsors
Renibus Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
2:1 randomization to receive RBT-9:Placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | baseline and 7 days, baseline and 28 days | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RBT-9 (90 mg) RBT-9 (90mg) will be administered intravenously over a 120-minute period on Day 1.
RBT-9 (90 mg): Subjects will receive a single dose and study duration will be approximately 60 days per subject. | 28 |
| Placebo 0.9% sodium chloride (normal saline) will be administered intravenously over a 120-minute period on Day 1.
0.9% sodium chloride (normal saline): Subjects will receive a single dose and study duration will be approximately 60 days per subject. | 14 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | RBT-9 (90 mg) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 15 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 27 Participants | 20 Participants |
| Age, Continuous | 57.6 Years STANDARD_DEVIATION 17.11 | 55 Years STANDARD_DEVIATION 16.66 | 53.6 Years STANDARD_DEVIATION 16.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 17 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 25 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) White | 6 Participants | 27 Participants | 21 Participants |
| Region of Enrollment United States | 14 participants | 42 participants | 28 participants |
| Sex: Female, Male Female | 9 Participants | 26 Participants | 17 Participants |
| Sex: Female, Male Male | 5 Participants | 16 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 28 | 2 / 14 |
| other Total, other adverse events | 6 / 28 | 4 / 14 |
| serious Total, serious adverse events | 3 / 28 | 1 / 14 |
Outcome results
Primary
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)
Time frame: baseline and 7 days, baseline and 28 days
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| RBT-9 (90 mg) | 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 | Day 7 | -1.0 units on a scale |
| RBT-9 (90 mg) | 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 | Day 28 | -1.2 units on a scale |
| Placebo | 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 | Day 7 | -0.0 units on a scale |
| Placebo | 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 | Day 28 | -0.6 units on a scale |
p-value: 0.0352Mixed Models Analysis
Comparison: Comparison made for Day 7 and Day 28p-value: 0.235Mixed Models Analysis