VERU-111 in the Treatment of SARS-Cov-2 Infection by Assessing Its Effect on the Proportion of Patients Who Die on Study (VERU-111)

Phase 3, Randomized, Placebo-Controlled, Efficacy and Safety 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 patients who die on study (prior to Day 60).

Study Overview

• Status: Completed
• Conditions: SARS-CoV Infection
• 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 9mg of VERU-111 or matching placebo orally or through nasogastric tube daily for up 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 die prior to Day 60.The total study duration for a subject from screening to follow up visit is planned to be 62 days. In addition to the safety of VERU-111, an evaluation of the efficacy of VERU-111 on SARS-CoV-2 (COVID-19) compared to the placebo control will be evaluated as part of the Independent Data Monitoring Committee (IDMC).

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1814
    • Hospital De Alta Compleijdad Cuenca Alta Nestor Kirchner
  • Buenos Aires, Argentina, B1942DOL
    • Hospital del Bicentenario de Esteban Echeverría
  • Buenos Aires, Argentina, C1039AAC
    • Center Sagrado Corazon
  • Buenos Aires, Argentina, C1180ABB
    • Sanatorio Güemes
  • Buenos Aires, Argentina, C1282AEL
    • Hospital De Infecciosas "Dr. Francisco Javier Muniz"
• Brazil
  • Botucatu, Brazil, 18618-687
    • Faculdade de Medicina de Botucatu - UNESP
  • Bragança Paulista, Brazil, 12916-542
    • Hospital Universitario Sao Francisco na Providencia de Deus
  • Campinas, Brazil
    • IPECC (Instituto De Pesquisa Clínica de Campinas)
  • Campinas, Brazil
    • Sociedade Hospital Angelina Caron
  • Curitiba, Brazil, 80010-030
    • Santa Casa de Curitiba
  • Niteroi, Brazil, 24020-096
    • Complexo Hospitalar de Niterói
  • Porto Alegre, Brazil, 90035-003
    • Hospital de Clínicas de Porto Alegre - Infectologia - Centro de Pesquisa Clínica
  • Porto Alegre, Brazil, 90610-000
    • Hospital Sao Luca Da PUCRS
  • Rio De Janeiro, Brazil
    • Hospital Universitario Cementino Fraga Filho
  • Sao Paulo, Brazil, 04501-000
    • IDOR - D'Or Institute for Research and Education
  • Sao Paulo, Brazil, 05403-000
    • INCOR - Instituto do Coração do Hospital das Clínicas da FMUSP
  • Sorocaba, Brazil, 18040-425
    • Hospital Miguel Soeiro Sorocaba
  • São Paulo, Brazil
    • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Fundação Pio XII - Hospital de Amor de Barretos
    • Campinas, Sao Paulo, Brazil, 13060-904
      • Hospital PUC Campinas
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • MHAT Blagoevgrad AD Department of Infectious Diseases
  • Haskovo, Bulgaria, 6304
    • Multiprofile Hospital for Active Treatment - Haskovo, Department of Infectious Diseases
  • Kardzhali, Bulgaria, 6600
    • Multiprofile Hospital for Active Treatment - Dr. Atanas Dafovski AD, Kardzhali, Department of Pneumology and Phthisiatry, Dept. of Pneumology & Phthisiatry
  • Pernik, Bulgaria, 2300
    • Specialized hospital for active treatment of pulmonary diseases -Pernik EOOD, Pernik
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment "Pulmed" OOD Plovid Rheumatology
  • Smolyan,, Bulgaria, 4700
    • MHAT Bratan Shukerov,Pulmonology Department
  • Sofia, Bulgaria, 1527
    • University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna-ISUL" EAD, Sofia,
  • Sofia, Bulgaria, 1606
    • Multiprofile Hospital for Active Treatment and Emergency Medicine
  • Stara Zagora, Bulgaria, 6003
    • University Multiprofile Hospital for Active Treatment "Professor Doctor Stoyan Kirkovich" AD, Stara Zagora, Clinic of Anaestheology and intensive care
• Colombia
  • Atlántico, Colombia, 080001
    • Fundación Hospital Universidad del Norte (Barranquilla)
  • Barranquilla, Colombia, 080020
    • Clinica de la Costa (Barranquilla)
  • Bogotá, Colombia, 111311
    • Fundación Cardioinfantil-Instituto de Cardiología
  • Cali, Colombia, 760042
    • Centro Medico Imbanaco de Cali S.A
  • Rionegro, Colombia, 050023
    • Sociedad Medica Rionegro- Clínica Somer (Rionegro)
• Mexico
  • Culiacán, Mexico, 80230
    • Hospital General de Culiacan
  • Zapopan, Mexico
    • Hospital General de Occidente
  • Nuevo Leon
    • San Nicolas de los Garza, Nuevo Leon, Mexico, 66465
      • Unidad Medica para la Salud Integral (UMSI)
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honor Health
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • St. Bernard's Medical Center
  • California
    • Chula Vista, California, United States, 91911
      • Velocity Clinical Research
    • La Mesa, California, United States, 91942
      • Velocity Clinical Research - San Diego
  • Florida
    • Miami, Florida, United States, 33155
      • Westchester General Hospital, Research Department
    • Tampa, Florida, United States, 33612
      • James A. Haley Veterans Hospital
  • Georgia
    • Marietta, Georgia, United States, 30060
      • WellStar Research Institute
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Benchmark Research
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • Methodist Hospital
    • Saint Paul, Minnesota, United States, 55426
      • Regions Hospital
  • New Jersey
    • Mullica Hill, New Jersey, United States, 08062
      • Inspira Medical Center Mullica Hill
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center, Institute for Clinical Research
    • Vineland, New Jersey, United States, 08360
      • Inspira Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Atrium Health Carolinas Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Stern Cardiovascular Foundation, Inc.
    • Memphis, Tennessee, United States, 38103
      • Regional One Health
    • Powell, Tennessee, United States, 37849
      • North Knoxville Medical Center
  • Texas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77024
      • HD Research (Memorial Hermann - Memorial City Medical Center)
    • Houston, Texas, United States, 77024
      • HD Research (Memorial Hermann Southeast Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provide informed consent from the subject or the subject's Legally Authorized Representative (LAR)
• Aged ≥18 years
• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test
• Patients with a WHO Ordinal Scale for Clinical Improvement score of 4 at high risk for ARDS, must have at least one of the known comorbidities for being at high risk, such as, Asthma (moderate to severe), Chronic Lung Disease, Diabetes, Hypertension, Severe Obesity (BMI ≥40), 65 years of age or older, primarily reside in a nursing home or long-term care facility, or immunocompromised and patients with a WHO Ordinal Scale for Clinical Improvement score of 5 or 6 regardless of presence of comorbidities.
• WHO Ordinal Scale for Clinical Improvement score of 4 (Oxygen by mask or nasal prongs), 5 (Non-invasive ventilation or high-flow oxygen) or 6 (Intubation and mechanical ventilation)
• Peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air at screening. If patient is on oxygen therapy at the time of presentation for screening and the SpO2 levels were ≤94% prior to introduction to oxygen therapy with proper documentation example EMT notes or ER/ED notes, then the patient is considered to have met this inclusion criterion. If patient is on oxygen therapy at the time of presentation for screening and the SpO2 levels prior to introduction to oxygen therapy are unknown, the patient may be considered to have met this inclusion criterion if oxygen therapy is removed and the SpO2 levels fall to ≤94%, then the patient is considered to have met this inclusion criterion. However, removal of the oxygen therapy should only be done if it is considered medically reasonable
• Subjects must agree to follow doctor's recommendation for oxygen supplementation

• Subjects must agree to use acceptable methods of contraception:

  • If female of childbearing potential or a male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6months 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 the female partner of a male subject has undergone documented tuballigation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository)should also be used
  • If 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
• Pregnant or currently breast feeding
• Participation in any other clinical trial of an experimental treatment for COVID- 19. Convalescent plasma, dexamethasone and remdesivir are allowed in this study.
• Concurrent treatment with other experimental agents with actual or possible direct acting antiviral activity against COVID-19is prohibited <24 hours prior to study drug dosing(except standard of care). Remdesivir, dexamethasone and convalescent plasma are allowed in the study.
• Requiring ventilation + additional organ support - pressors, RRT, ECMO(WHO Ordinal Scale for Clinical Improvement - Score of 7). NOTE: short term (PRN) use of pressors is allowed
• Alanine Aminotransferase (ALT) or aspartate aminotransferase(AST) >3X 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
• History of hepatitis - (Hepatitis B and C) NOTE: treated and controlled hepatitis C is allowed
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 9mg of VERU-111 Oral daily; 9mg of VERU-111	Drug: VERU-111; Subjects in the VERU-111 treatment groups will receive standard of care, plus oral daily VERU-111 9mg for 21 days or until released from hospital.; Other Names: Sabizabulin
No Intervention: Placebo Capsule once daily; Subjects in the Placebo treatment group will receive standard of care, plus a placebo capsule for 21 days or until released from hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Sabizabulin in the Treatment of SARS-CoV-2 Infection by Assessing Its Effect on the Proportion of Patients Who Died on Study.	Efficacy of VERU-111 in the treatment of SARS-Cov- 2 Infection by assessing its effect on the proportion of patients who die on study (prior to Day 60).	Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects That Are Alive Without Respiratory Failure at Day 15, Day 22 and Day 29.	The proportion of subjects that are alive without respiratory failure at Day 15, Day 22 and 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 15, Day 22, Day 29

Collaborators and Investigators

• Sponsor: Veru Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2021
• Primary Completion (Actual): July 6, 2022
• Study Completion (Actual): July 6, 2022

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (Actual): April 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Severe Acute Respiratory Syndrome; Infections
• Other Study ID Numbers: V3011902

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