This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter, dose escalation and proof-of-concept study to evaluate the safety and efficacy of razuprotafib, administered 3 times daily (TID) (every 8 hours [Q8H]), in hospitalized subjects with moderate to severe Coronavirus disease 2019 (COVID-19) receiving standard of care therapy. The study was planned to include 2 parts with Part 1 comprising the dose escalation period of the study and Part 2 comprising the proof-of-concept safety and efficacy period of the study.
Part 1 was to be a 2-step dose escalation that included approximately 60 subjects. Part 1,
Step 1 was to include 30 subjects, and Part 1, Step 2 was to include 30 subjects. Part 1 was
designed to primarily focus on safety; however, efficacy data was to be collected and
analyzed as well.
Despite the Data Review Committee (DRC) recommendation to continue the study, after
completion of Part 1, Step 1, the Sponsor elected to discontinue the study due to
business-related reasons. Recruitment challenges and slow site startup led to delays in
completing the study in a practical timeframe, and were the primary reasons to discontinue
the study. No further subjects were recruited after Part 1, Step 1 completion. A full
analysis of the data from Part 1, Step 1 was conducted and is presented in this report.
Part 1, Step 2 and Part 2 was not conducted.
Drug: Razuprotafib Subcutaneous Solution
Up to 3 daily dose levels of Razuprotafib Subcutaneous Solution will be evaluated. Doses will be administered subcutaneously three times daily (Q8H) for 7 days.
Other Name: Razuprotafib 10 mg and 20 mg solution
Drug: Placebo Subcutaneous Solution
Matched vehicle-controlled placebo solution will be administered subcutaneously three times daily (Q8H) for 7 days
Other Name: Placebo comparator
Inclusion Criteria:
1. Ability to understand and provide informed consent;
2. Males and non-pregnant females 18 years of age or older at the time of Screening;
3. Laboratory-confirmed active SARS-CoV-2 infection within 72 hours prior to
randomization, or (if testing results cannot be obtained) by evidence of progressive
disease suggestive of ongoing SARS-CoV-2 infection;
4. Females of childbearing potential must be willing to completely abstain or agree to
use a highly effective method of contraception through Day 28; and have a negative
urine pregnancy test during Screening;
5. Currently hospitalized, receiving standard of care therapy for COVID-19, and meets the
criteria for moderate or severe COVID-19, as follows: Moderate = symptoms of moderate
illness with COVID-19, which could include any symptom of mild illness or shortness of
breath with exertion and with respiratory rate at 20 or greater breaths/min,
Peripheral capillary oxygen saturation (SpO2) >93% on room air at sea level, or heart
rate at 90 or greater beats/min; Severe = symptoms suggestive of severe systemic
illness with COVID-19, which could include any symptom of moderate illness, shortness
of breath at rest, or respiratory distress, and respiratory rate at 30 or greater
breaths/min, heart rate at 125 or greater beats/min, or SpO2 >93% on room air at sea
level or (partial pressure of oxygen:fraction of inspired oxygen (PaO2:FiO2) <300.
Exclusion Criteria:
1. Inability to initiate study drug within 12 hours after randomization;
2. Female of childbearing potential who is unable or unwilling to forego breastfeeding
through Day 28;
3. Systolic blood pressure <100 mmHg;
4. In shock or requiring pressor support;
5. Respiratory failure, defined as subjects who are on mechanical ventilation; are
receiving oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen
delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of
delivered oxygen of 0.5 or greater), noninvasive positive pressure ventilation, or
extracorporeal membrane oxygenation (ECMO); or have a clinical diagnosis of
respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding
therapies not able to be administered in setting of resource limitation);
6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper
limit of normal (ULN);
7. Total bilirubin >2 × ULN;
8. Estimated glomerular filtration rate <30 mL/min or receiving hemodialysis or
hemofiltration;
9. Moribund subject not expected to survive 24 hours in the opinion of the treating
clinical team;
10. Any concurrent serious medical condition (eg, active malignancies on chemotherapy,
post organ transplant, end stage congestive heart failure) or not likely to respond to
treatment;
11. Decision to withhold life-sustaining treatment; Note: In the event of cardiac arrest,
the decision to withhold cardiopulmonary resuscitation only does not fulfill this
exclusion criterion.
12. Use of cytochrome P450 (CYP) 2 subfamily C, polypeptide 8 (2C8) substrates (eg,
repaglinide, paclitaxel, or cerivastatin) or CYP3A4 substrates (eg, amlodipine,
budesonide, dasabuvir, enzalutamide, imatinib, lopinavir, loperamide, saquinavir,
sildenafil, midazolam, or montelukast);
13. Use of CYP2C8 inhibitors (eg, gemfibrozil, fluvoxamine, or ketoconazole);
14. Participation in another investigational study during the present study through the
last visit (Day 28); or
15. Previous randomization in this study.
University of Southern California
Los Angeles, California, United States
University of California- Irvine Medical Center
Orange, California, United States
MedStar Georgetown University Hospital
Washington, District of Columbia, United States
Snake River Research
Idaho Falls, Idaho, United States
University of Minnesota
Minneapolis, Minnesota, United States
University of Cincinnati
Cincinnati, Ohio, United States
Rhode Island Hospital
Providence, Rhode Island, United States