2019 Novel Coronavirus Infection, Adult Respiratory Distress Syndrome, COVID-19 Virus Infection, Respiratory Distress Syndrome, Adult, SARS Coronavirus 2 Infection, SARS-CoV-2 Infection
Conditions
Brief summary
This trial will study the use of USB002 given as an intravenous infusion in patients with respiratory distress due to infection with COVID-19.
Interventions
DRUGUSB002
USB002 is pharmaceutically formulated Angiotensin 1-7 \[A(1-7)\], a non-hypertensive derivative of Angiotensin-II (A-II), and is suspended in a vehicle as a sterile solution of USB002. Depending upon cohort assignment, subjects in the USB002 group will receive one of four doses of USB002 administered intravenously (IV).
DRUGPlacebo
The placebo formulation will be the USB002 formulated solution without the addition of A(1-7). The placebo will be administered intravenously (IV).
Sponsors
US Biotest, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent from patient or legal representative; 2. Age 18 or greater; 3. Positive reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 (≤10 days); 4. Respiratory rate \> 20 RR; 5. SpO2 \< 94% on room air, requiring supplemental oxygen, requiring invasive mechanical ventilation, or requiring ECMO; 6. Chest X-ray confirming bilateral pulmonary infiltrates; 7. Body mass index of ≤ 40 units/kg/m2; 8. Adequate method of birth control.
Exclusion criteria
1. Terminally ill patients due to underlying cardiac, cancer or severe debilitating neurological disease including coma; 2. Hospitalization expected to be \< 96 hours due to medical improvement; 3. Interstitial lung disease; 4. Correction of QTc values obtained by 12 lead EKG using Fredericia's formula (QTcF) \> 450 ms; 5. History of hypotension (mean arterial blood pressure \< 65 mmHg), unrelated to CoVID-19 infection; 6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 times upper limit of normal; 7. Participating concurrently on another clinical trial for the experimental treatment of COVID-19; 8. Active chemotherapy use; 9. Pregnant and/or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | Day 1 to Day 70 (or date of final measurement, if sooner) | Treatment emergent adverse events (including changes in laboratory assessments, physical examination findings, and vital signs) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| USB002 90 ug/kg/Day Subjects received standard of care plus a continuous IV infusion of 90 ug/kg/day USB002 for up to 96 hours. | 3 |
| USB002 300 ug/kg/Day Subjects received standard of care plus a continuous IV infusion of 300 ug/kg/day USB002 for up to 96 hours. | 3 |
| USB002 600 ug/kg/Day Subjects received standard of care plus a continuous IV infusion of 600 ug/kg/day USB002 for up to 96 hours. | 3 |
| USB002 900 ug/kg/Day Subjects received standard of care plus a continuous IV infusion of 900 ug/kg/day USB002 for up to 96 hours. | 2 |
| Placebo Subjects received standard of care plus a continuous IV infusion of USB002 placebo for up to 96 hours. | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Telemed not done due to internal miscommunication. | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | USB002 90 ug/kg/Day | Total | Placebo | USB002 900 ug/kg/Day | USB002 600 ug/kg/Day | USB002 300 ug/kg/Day |
|---|---|---|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 18.25 | 57.9 years STANDARD_DEVIATION 16.2 | 59.8 years STANDARD_DEVIATION 8.18 | 78.5 years STANDARD_DEVIATION 0.71 | 61.0 years STANDARD_DEVIATION 12.17 | 57.0 years STANDARD_DEVIATION 8.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 10 Participants | 5 Participants | 0 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 11 Participants | 5 Participants | 2 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 20 Participants | 10 Participants | 2 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 21 participants | 10 participants | 2 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 16 Participants | 10 Participants | 1 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 3 | 1 / 3 | 1 / 2 | 1 / 10 |
| other Total, other adverse events | 2 / 3 | 3 / 3 | 2 / 3 | 2 / 2 | 8 / 10 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 1 / 3 | 1 / 2 | 1 / 10 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Treatment emergent adverse events (including changes in laboratory assessments, physical examination findings, and vital signs)
Time frame: Day 1 to Day 70 (or date of final measurement, if sooner)
Population: All enrolled subjects who received a USB002 or Placebo infusion were included in the analysis population for all outcomes analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| USB002 90 ug/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAE) | 2 Participants |
| USB002 300 ug/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAE) | 3 Participants |
| USB002 600 ug/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAE) | 2 Participants |
| USB002 900 ug/kg/Day | Number of Participants With Treatment Emergent Adverse Events (TEAE) | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | 8 Participants |