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

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)

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).

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome, Adult
• Intervention / Treatment: Drug: Veru-111

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • Methodist Hospital
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • New Jersey
    • Vineland, New Jersey, United States, 08360
      • Inspira Medical Center
  • Texas
    • Houston, Texas, United States, 77024
      • Memorial Hermann Memorial City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide informed consent
2. Be able to communicate effectively with the study personnel
3. Aged ≥18 years
4. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test
5. 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
6. Peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air at screening

7. 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
8. Subject is willing to comply with the requirements of the protocol through the end of the study

Exclusion Criteria:

1. Known hypersensitivity or allergy to colchicine
2. Participation in any other clinical trial of an experimental treatment for COVID-19
3. 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.
4. Requiring mechanical ventilation at screening
5. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) >2 X upper limit of normal (ULN)
6. Total bilirubin > ULN
7. Creatinine clearance < 60 mL/min
8. 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
9. Moderate to severe renal impairment
10. Hepatic impairment
11. Positive for HbsAg, or HCV antibodies at screening
12. 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
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsules	Drug: Veru-111; Respiratory Distress Syndrome, Adult; Other Names: Bisindole
Experimental: Veru-111 18 mg; Veru-111 18mg capsules	Drug: Veru-111; Respiratory Distress Syndrome, Adult; Other Names: Bisindole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Veru Inc.
• Investigators: Study Director: Barnette, Veru Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): December 18, 2020
• Study Completion (Actual): August 13, 2021

Study Registration Dates

• First Submitted: May 13, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: V0211901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No