A Dose Escalation and Dose Expansion Study of NOX66 in the Treatment of COVID-19

Study Overview
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Brief Summary
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Phase Ib, open-label, multicenter, study of NOX66, given rectally to hospitalized patients with moderate systemic illness due to COVID-19 infection at high risk of developing severe sepsis / septic shock.

Official Title
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A Dose Escalation and Dose Expansion Study of NOX66 in the Treatment of COVID-19 Infection (NOXCOVID)

Conditions
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Covid19

Intervention / Treatment
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* Drug: NOX66


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Hospitalized patient with clinically diagnosis of SARS-CoV-2 virus infection per World Health Organization criteria including positive nucleic acid test of any specimen (e.g., respiratory, blood, or other bodily fluid) within 2 weeks prior to screening.{Other confirmatory test results will be accepted upon approval from Sponsor/CRO Medical Monitor prior to enrolment}. Symptoms suggestive of moderate systemic illness with COVID-19, which could include any of the following symptoms: fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath at rest, or respiratory distress. Clinical signs indicative of moderate systemic COVID-19 illness (with high risk of developing severe ARDS/septic shock) with an aggregate of NEWS-2 score of 4-6 or 3 in one single parameter. Key Exclusion Criteria: Patients who meet any of the following criteria will be disqualified from entering the study: Patients who require endotracheal intubation and mechanical ventilation, 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 ≥ 0.5), non-invasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure. Presence of any of the following abnormal laboratory values at screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 x upper limit of normal (ULN), platelets <50,000/µL. Treatment with anti-IL 6, anti-IL-6R antagonists, or with Janus kinase inhibitors in the past 30 days or plans to receive during the study period. Current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents. Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day. History of, or current autoimmune or inflammatory systemic or localized disease(s) other than rheumatoid arthritis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1 Dose Escalation: 400mg, 600mg, 800mg, 1200mg & 1800mg Part 2 Dose Expansion : Recommended Phase 2 Dose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort 1 - NOX66 400mg<br>NOX66 400 mg suppository OD | Drug: NOX66<br>* NOX66 Suppository<br>|
| Experimental: Dos Escalation Cohort 2 - NOX66 600mg<br>NOX66 600 mg suppository OD | Drug: NOX66<br>* NOX66 Suppository<br>|
| Experimental: Dose Escalation Cohort 3 - NOX66 800mg<br>NOX66 800 mg daily (400 mg suppository BID) | Drug: NOX66<br>* NOX66 Suppository<br>|
| Experimental: Dose Escalation Cohort 4 - NOX66 1200mg<br>NOX66 1200 mg daily (600 mg suppository BID) | Drug: NOX66<br>* NOX66 Suppository<br>|
| Experimental: Dose Escalation Cohort 5 - NOX66 1800mg<br>NOX66 1800 mg daily (600 mg suppository TID) | Drug: NOX66<br>* NOX66 Suppository<br>|
| Experimental: Dose Expansion - NOX66 Recommended Phase 2 Dose<br>Dose Expansion: NOX66 RP2D | Drug: NOX66<br>* NOX66 Suppository<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Routine safety monitoring during the study period | 60 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of National Early Warning Score 2 units from baseline | Measurement of 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness) to assess overall clinical condition. | 60 Days | 
| Change in WHO-9 point ordinal scale | Assessment of WHO-9 point ordinal scale for clinical improvement (i.e., 0 = uninfected and 8 = death) category ordinal scale of clinical status from admission. | 60 Days |