Clinical Trial of Efficacy and Safety of Oral Drug in Adult Patients With COVID-19

Study Overview
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Brief Summary
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This is a Phase 1, multi-center, dose escalation study that is followed by a Phase 2 randomized, double-blind, placebo-controlled study of the safety and efficacy of WP1122 administered q12h ±1 hr PO in adult patients with COVID-19 who require hospitalization with respiratory support. The Phase 1 component will enroll COVID-19 positive patients who are symptomatic and the Phase 2 component will enroll adults with COVID-19 who require hospitalization for respiratory support and those patients requiring intubation with mechanical ventilation.

Official Title
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A Phase 1/2, Dose Escalation, and Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Oral WP1122 in Adult Patients With Advanced Coronavirus Disease 2019 (COVID-19)

Conditions
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COVID-19, Mechanical Ventilation Complication, COVID-19 Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: WP1122


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age at Screening; Confirmed SARS-CoV-2 viral infection by polymerase chain reaction (PCR) within 48 hours prior to first administration; Hospitalized patients who are symptomatic (Phase 1) and require respiratory support (Phase 2); Off antiviral medications for at least 7 days prior to first dose of study drug. (Antiviral agents directed for another ongoing non-SARS-COV-2 infection such as Valtrex (valacyclovir hydrochloride) for herpes simplex virus lesions are allowed; Written informed consent from the patient or legally authorized representative (LAR), if the patient is not able to provide informed consent due to severity of illness; Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening; WCBP must agree to abstain from sex or use an adequate method of contraception* from the time of informed consent through the final in-person evaluations at Day 38 (± 3 days); Males must abstain from sex with WCBP or use an adequate method of contraception* from the time of informed consent through the final in-person evaluations at Day 38 (± 3 days). Exclusion Criteria: On extracorporeal membrane oxygenation (ECMO); SpO2/FiO2<100 while on respiratory support Use of high dose of >1.0 mcg/kg/min of norepinephrine or need for rescue therapy with vasopressin; Bacterial or fungal infection, except for mild cutaneous infection or sinus infection. Asymptomatic bacteriuria or airway colonization of bacteria is not an exclusion criteria; Pregnant or lactating; Alanine aminotransferase (ALT), Aspartate aminotransaminase (AST) ≥5 times the upper limited of normal (ULN), bilirubin >2 times the ULN (unless previously diagnosed with Gilbert's Syndrome), or International Normalised Ratio (INR) outside of normal limits (unless prolonged due to taking anticoagulants) at Screening Estimated glomerular filtration rate (eGFR) <30 mL/min; Any condition which, in the opinion of the Investigator, places the patient at unacceptable risk if they were to participate in the study; Clinically relevant serious co-morbid medical conditions including, but not limited to, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, severe hepatic impairment, active central nervous system (CNS) disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV), active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements; Treatment with any immunosuppressive therapy other than corticosteroids within 30 days prior to Screening; Treatment with another investigational drug within 30 days or 5 half-lives of drug prior to Screening, whichever is longer; Prior treatment with the study drug (WP1122); Known hypersensitivity to the inactive ingredients of the study drug (WP1122) or placebo. Participation in another clinical study in less than 1 year (unless justified participation by the principal investigator)

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WP1122<br>Experimental drug with Concentration 100mg/mL - administered q12h PO for 10 days | Drug: WP1122<br>* Doses from 8 mg/kg will be increased in doubling increments up to 64 mg/kg in the dose escalation Phase 1 portion of the study, administered orally (PO) for 10 days q12h ±1h. The dose in Phase 2 will utilize the Maximum Tolerated Dose (MTD) established in Phase 1 and also administered PO q12h ± 1h for 10 days.<br>|
| Placebo Comparator: placebo<br>Placebo Administered q12h PO for 10 days | Drug: WP1122<br>* Doses from 8 mg/kg will be increased in doubling increments up to 64 mg/kg in the dose escalation Phase 1 portion of the study, administered orally (PO) for 10 days q12h ±1h. The dose in Phase 2 will utilize the Maximum Tolerated Dose (MTD) established in Phase 1 and also administered PO q12h ± 1h for 10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the Area Under the Curve (AUC) of Interleukin-6 (IL-6) concentrations | Co-primary efficacy endpoints will be utilized in a sequential analysis manner. The first primary efficacy endpoint will be the difference in the AUC of IL-6 concentrations from Baseline (Day 0) through Day 10. For patients who do not have IL-6 values out to Day 10, a last observation carried forward technique will be utilized | through the last day of observation (day 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 negativity | The time to COVID-19 negativity in patients receiving WP1122 or placebo | through the last day of observation (day 10) |