Evaluation of the Safety and Efficacy of Razuprotafib in Hospitalized Subjects With Coronavirus Disease 2019
Condition: COVID-19; Acute Respiratory Distress Syndrome (ARDS)
MeSH terms: COVID-19; Coronavirus Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
Intervention: Razuprotafib Subcutaneous Solution; Placebo Subcutaneous Solution
Intervention description: 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.; Matched vehicle-controlled placebo solution will be administered subcutaneously three times daily (Q8H) for 7 days
Intervention MeSH terms: Pharmaceutical Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: 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. Although The Data Review Committee (DRC) recommended to continue with the study after the completion of Part 1, Step 1, the Sponsor elected to discontinue the study due to business-related reasons.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: COVID-19; ARDS; Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Summary:

      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.
    

Eligibility criteria:

        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.