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

• Sponsor: Veru Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04388826
• Collaborator: (none)
• Enrollment: 39
• Locations: 5
• Arms: 2
• Actual Duration (Months): 13.8
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome, Adult	Drug: Veru-111	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Placebo-ControlledRandomized Placebo-Controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double Blind Randomized Placebo-Controlled
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Jun 18, 2020
• Actual Primary Completion Date: Dec 18, 2020
• Actual Study Completion Date: Aug 13, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Subjects That Are Alive Without Respiratory Failure at Day 29. [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

Secondary Outcome Measures

1. World Health Organization Ordinal Scale Clinical Improvement [Day 29]

   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

2. Normalization of Fever and Oxygen [Day 15, Day 22, and Day 29]

   Proportion of subjects with normalization of fever and oxygen saturation through

3. Discharge From Hospital [Day 15 and Day 22]

   Percentage of subjects discharged from hospital

4. Patients Alive and Free of Respiratory Failure [Day 15, and Day 22]

   Proportion of patients alive and free of respiratory failure

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth	Scottsdale	Arizona	United States	85258
2	Methodist Hospital	Saint Louis Park	Minnesota	United States	55426
3	Regions Hospital	Saint Paul	Minnesota	United States	55101
4	Inspira Medical Center	Vineland	New Jersey	United States	08360
5	Memorial Hermann Memorial City Hospital	Houston	Texas	United States	77024

Sponsors and Collaborators

• Veru Inc.

Investigators

• Study Director: Barnette, Veru Inc.

Study Documents (Full-Text)

• Study Protocol - Sep 25, 2020
• Statistical Analysis Plan - Feb 9, 2021

More Information

Publications

None provided.

• Responsible Party: Veru Inc.
• ClinicalTrials.gov Identifier: NCT04388826
• Other Study ID Numbers: V0211901
• First Posted: May 14, 2020
• Last Update Posted: Nov 24, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome

Study Results

Participant Flow

Arm/Group Title	Veru-111 18 mg QD	Placebo QD
Arm/Group Description	Veru-111 18mg capsules Veru-111: Respiratory Distress Syndrome, Adult	Placebo capsules Veru-111: Respiratory Distress Syndrome, Adult
Period Title: Overall Study
STARTED	19	20
COMPLETED	15	18
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Number of Patients Exposed to Veru-111 18 mg	Number of Patients Exposed to Placebo	Total
Arm/Group Description	Veru-111 18mg capsules Veru-111: Respiratory Distress Syndrome, Adult	Placebo capsules Veru-111: Respiratory Distress Syndrome, Adult	Total of all reporting groups
Overall Participants	19	20	39
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.3 (11.40)	57.8 (13.32)	58.5 (12.28)
Sex: Female, Male (Count of Participants)
Female	9 47.4%	3 15%	12 30.8%
Male	10 52.6%	17 85%	27 69.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 31.6%	8 40%	14 35.9%
Not Hispanic or Latino	13 68.4%	12 60%	25 64.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 5%	1 2.6%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 5%	1 2.6%
Black or African American	0 0%	1 5%	1 2.6%
White	19 100%	16 80%	35 89.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 5%	1 2.6%
Region of Enrollment (participants) [Number]
United States	19 100%	20 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects That Are Alive Without Respiratory Failure at Day 29.
Description	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
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

Responders

Arm/Group Title	Veru-111 18 mg	Placebo
Arm/Group Description	Veru-111 18mg capsules Veru-111: Respiratory Distress Syndrome, Adult	Placebo capsules Veru-111: Respiratory Distress Syndrome, Adult
Measure Participants	19	20
Count of Participants [Participants]	17 89.5%	14 70%

2. Secondary Outcome

Title	World Health Organization Ordinal Scale Clinical Improvement
Description	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
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

World Health Organization Ordinal Scale for clinical improvement (Eight Point Ordinal Scale)-With Last Observation Carried Forward Values

Arm/Group Title	Veru-111 18 mg	Placebo
Arm/Group Description	Veru-111 18mg capsules Veru-111: Respiratory Distress Syndrome, Adult	Placebo capsules Veru-111: Respiratory Distress Syndrome, Adult
Measure Participants	19	20
Mean (Standard Deviation) [Units on WHO COVID Scale]	-1.7 (1.49)	-1.1 (2.42)

3. Secondary Outcome

Title	Normalization of Fever and Oxygen
Description	Proportion of subjects with normalization of fever and oxygen saturation through
Time Frame	Day 15, Day 22, and Day 29

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Discharge From Hospital
Description	Percentage of subjects discharged from hospital
Time Frame	Day 15 and Day 22

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Patients Alive and Free of Respiratory Failure
Description	Proportion of patients alive and free of respiratory failure
Time Frame	Day 15, and Day 22

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	62 Days
Arm/Group Title	Veru-111 18 mg		Placebo
Arm/Group Description	Veru-111 18mg capsules Veru-111: Respiratory Distress Syndrome, Adult		Placebo capsules Veru-111: Respiratory Distress Syndrome, Adult
All Cause Mortality
	Veru-111 18 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		5/20 (25%)
Serious Adverse Events
	Veru-111 18 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)		5/20 (25%)
Cardiac disorders
Cardiac Arrest	1/19 (5.3%)	1	0/20 (0%)	0
Infections and infestations
Septic Sock	1/19 (5.3%)	1	2/20 (10%)	2
COVID-19	0/19 (0%)	0	1/20 (5%)	1
Nervous system disorders
Encephalopathy	0/19 (0%)	0	1/20 (5%)	1
Renal and urinary disorders
Acute Kidney Injury	0/19 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/19 (5.3%)	1	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Veru-111 18 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/19 (63.2%)		12/20 (60%)
Gastrointestinal disorders
Constipation	5/19 (26.3%)	5	2/20 (10%)	2
Infections and infestations
Septic Shock	1/19 (5.3%)	1	3/20 (15%)	3
Investigations
Alanine aminotransferase increased	2/19 (10.5%)	2	2/20 (10%)	2
Aspartate aminotransferase increased	3/19 (15.8%)	3	1/20 (5%)	1
Renal and urinary disorders
Acute Kidney Injury	0/19 (0%)	0	2/20 (10%)	2
Respiratory, thoracic and mediastinal disorders
Pneumomediastinum	0/19 (0%)	0	2/20 (10%)	2
Pneumothorax	1/19 (5.3%)	1	3/20 (15%)	4
Respiratory Failure	0/19 (0%)	0	4/20 (20%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.