COVID-19 Treatment of Severe Acute Respiratory Syndrome With Veru-111

Study Overview
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Brief Summary
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To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO).

Detailed Description
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This study is a multicenter, randomized, placebo-control, efficacy and safety study of VERU-111 for the treatment of COVID-19. Subjects will receive either 18 mg of VERU-111 or matching placebo orally or through nasogastric tube daily for to 21 days or until the subject is discharged from the hospital, whichever comes first. The primary efficacy endpoint of the study will be the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO). The total study duration for a subject from screening to follow up visit is planned to be 62 days. An evaluation of the effect of VERU-111 on SARS-CoV-2 (COVID-19) compared to the placebo control will be evaluated after the last subject has completed Day 22. This will allow for the decision to move to Phase 3 more quickly if the Phase 2 portion of the study shows a clinically relevant difference in the proportion of subjects that are alive without respiratory failure at Day 22 in the VERU-111 treated groups compared to the Placebo treatment group and VERU-111 is well tolerated in the study.

Official Title
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Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS)

Conditions
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Respiratory Distress Syndrome, Adult

Intervention / Treatment
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* Drug: Veru-111


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide informed consent Be able to communicate effectively with the study personnel Aged ≥18 years Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test Patients at high risk for ARDS, with known comorbidities for being at high risk, such as, Asthma (moderate to severe), Chronic Lung Disease, Diabetes, Chronic Kidney Disease being treated with dialysis, Severe Obesity (BMI ≥40), 65 years of age or older, primarily reside in a nursing home or long-term care facility, immunocompromised Peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air at screening Subjects must agree to use acceptable methods of contraception If subject is female or the male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) If female subject or the female partner of a male subject has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used If female subject or the female partner of a male subject has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used Subject is willing to comply with the requirements of the protocol through the end of the study Exclusion Criteria: Known hypersensitivity or allergy to colchicine Participation in any other clinical trial of an experimental treatment for COVID-19 Concurrent treatment with other experimental agents with actual or possible direct acting antiviral activity against COVID-19 is prohibited < 24 hours prior to study drug dosing (except standard of care) Remdesivir and convalescent plasma is allowed as standard of care. Requiring mechanical ventilation at screening Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) >2 X upper limit of normal (ULN) Total bilirubin > ULN Creatinine clearance < 60 mL/min Documented medical history of liver disease, including but not limited to, prior diagnosis of hepatitis of any etiology, cirrhosis, portal hypertension, or confirmed or suspected esophageal varices Moderate to severe renal impairment Hepatic impairment Positive for HbsAg, or HCV antibodies at screening Any comorbid disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk Participants must agree to refrain from prolonged exposure to the sun or agree to use at least SPF 50 on all exposed skin and protective clothing during prolonged sun exposure throughout participation in this study and/or treatment with VERU-111.

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
Interventional Model Description: Randomized Placebo-Controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Veru-111 18 mg<br>Veru-111 18mg capsules | Drug: Veru-111<br>* Respiratory Distress Syndrome, Adult<br>* Other names: Bisindole;|
| Placebo Comparator: Placebo<br>Placebo capsules | Drug: Veru-111<br>* Respiratory Distress Syndrome, Adult<br>* Other names: Bisindole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects That Are Alive Without Respiratory Failure at Day 29. | To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision making is driven solely by resource limitation | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| World Health Organization Ordinal Scale Clinical Improvement | Improvement on the World Health Organization Ordinal Scale for Clinical Improvement. 8-point ordinal scale (WHO scale from 0 to 8). Lower value equals better while higher value equals worse Score of 0 Uninfected No clinical or virologic evidence of infection Score of 1 Ambulatory No limitation of activities Score of 2 Limitation of activities Score of 3 Hospitalized, no oxygen therapy Score of 4 Oxygen by mask or nasal prongs Score of 5 Non-invasive ventilation or high-flow oxygen Score of 6 Intubation and mechanical ventilation Score of 7 Ventilation + additional organ support - pressors, RRT, ECMO Score of 8 Death | Day 29 | 
| Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Proportion of subjects with normalization of fever and oxygen saturation through. Responders are subjects who have been discharged from the hospital or has fever normalization maintained for at least 24 hours AND peripheral capillary oxygen saturation (SPO2) greater than 94% sustained for 24 hours is observed at the time of the visit. Non-responders are subjects who died before the visit or do not meet both criteria of the end point at the time of the visit. | Day 15, Day 22 and Day 29 | 
| Proportion of Subjects Alive and Discharged From Hospital by Visit | Proportion of subjects alive and discharged from hospital by visit. Responders are subjects who are alive and have been discharged from the hospital at the time of the visit. (Non-responders are subjects who died before the visit or in the hospital at the time of the visit). | Day 15, Day 22 and Day 29 | 
| Patients Alive and Free of Respiratory Failure | Proportion of patients alive and free or respiratory failure | Day 15 and Day 22 |