Clinical trial NCT04842747: VERU-111 in the Treatment of SARS-Cov-2 Infection by Assessing Its Effect on the Proportion of Patients Who Die on Study
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-CoV Infection
Lead sponsor: Veru Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-13
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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. Subjects in the Placebo treatment group will receive standard of care, plus a placebo capsule for 21 days or until released from hospital.
Primary purpose: TREATMENT

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 patients who die on study (prior to Day 60).

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).

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of Sabizabulin in the Treatment of SARS-CoV-2 Infection by Assessing Its Effect on the Proportion of Patients Who Died on Study.
timeFrame: Day 60
Secondary outcomes:
measure: The Proportion of Subjects That Are Alive Without Respiratory Failure at Day 15, Day 22 and Day 29.
timeFrame: Day 15, Day 22, Day 29
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: Jonesboro
country: United States
facility: St. Bernard's Medical Center
state: Arkansas
city: Chula Vista
country: United States
facility: Velocity Clinical Research
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research - San Diego
state: California
city: Miami
country: United States
facility: Westchester General Hospital, Research Department
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans Hospital
state: Florida
city: Marietta
country: United States
facility: Wellstar Research Institute
state: Georgia
city: Covington
country: United States
facility: Benchmark Research
state: Louisiana
city: Saint Louis Park
country: United States
facility: Methodist Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Mullica Hill
country: United States
facility: Inspira Medical Center Mullica Hill
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center, Institute for Clinical Research
state: New Jersey
city: Vineland
country: United States
facility: Inspira Medical Center
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health Carolinas Medical Center
state: North Carolina
city: Germantown
country: United States
facility: The Stern Cardiovascular Foundation, Inc.
state: Tennessee
city: Memphis
country: United States
facility: Regional One Health
state: Tennessee
city: Powell
country: United States
facility: North Knoxville Medical Center
state: Tennessee
city: Houston
country: United States
facility: HD Research (Memorial Hermann - Memorial City Medical Center)
state: Texas
city: Houston
country: United States
facility: HD Research (Memorial Hermann Southeast Hospital)
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital De Alta Compleijdad Cuenca Alta Nestor Kirchner
city: Buenos Aires
country: Argentina
facility: Hospital del Bicentenario de Esteban Echeverría
city: Buenos Aires
country: Argentina
facility: Center Sagrado Corazon
city: Buenos Aires
country: Argentina
facility: Sanatorio Güemes
city: Buenos Aires
country: Argentina
facility: Hospital De Infecciosas "Dr. Francisco Javier Muniz"
city: Barretos
country: Brazil
facility: Fundacao Pio XII - Hospital de Amor de Barretos
state: Sao Paulo
city: Campinas
country: Brazil
facility: Hospital PUC Campinas
state: Sao Paulo
city: Botucatu
country: Brazil
facility: Faculdade de Medicina de Botucatu - UNESP
city: Bragança Paulista
country: Brazil
facility: Hospital Universitário São Francisco na Providencia de Deus
city: Campinas
country: Brazil
facility: IPECC (Instituto De Pesquisa Clínica de Campinas)
city: Campinas
country: Brazil
facility: Sociedade Hospital Angelina Caron
city: Curitiba
country: Brazil
facility: Santa Casa de Curitiba
city: Niteroi
country: Brazil
facility: Complexo Hospitalar de Niteroi
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre - Infectologia - Centro de Pesquisa Clínica
city: Porto Alegre
country: Brazil
facility: Hospital Sao Luca Da PUCRS
city: Rio De Janeiro
country: Brazil
facility: Hospital Universitario Cementino Fraga Filho
city: Sao Paulo
country: Brazil
facility: IDOR - D'Or Institute for Research and Education
city: Sao Paulo
country: Brazil
facility: Incor - Instituto do Coração do Hospital das Clínicas da FMUSP
city: Sorocaba
country: Brazil
facility: Hospital Miguel Soeiro Sorocaba
city: São Paulo
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
city: Blagoevgrad
country: Bulgaria
facility: MHAT Blagoevgrad AD Department of Infectious Diseases
city: Haskovo
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Haskovo, Department of Infectious Diseases
city: Kardzhali
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Dr. Atanas Dafovski AD, Kardzhali, Department of Pneumology and Phthisiatry, Dept. of Pneumology & Phthisiatry
city: Pernik
country: Bulgaria
facility: Specialized hospital for active treatment of pulmonary diseases -Pernik EOOD, Pernik
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Pulmed" OOD Plovid Rheumatology
city: Smolyan,
country: Bulgaria
facility: MHAT Bratan Shukerov,Pulmonology Department
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna-ISUL" EAD, Sofia,
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment and Emergency Medicine
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Professor Doctor Stoyan Kirkovich" AD, Stara Zagora, Clinic of Anaestheology and intensive care
city: Atlántico
country: Colombia
facility: Fundación Hospital Universidad del Norte (Barranquilla)
city: Barranquilla
country: Colombia
facility: Clinica de la Costa (Barranquilla)
city: Bogotá
country: Colombia
facility: Fundación Cardioinfantil-Instituto de Cardiología
city: Cali
country: Colombia
facility: Centro Medico Imbanaco de Cali S.A
city: Rionegro
country: Colombia
facility: Sociedad Medica Rionegro- Clínica Somer (Rionegro)
city: San Nicolas de los Garza
country: Mexico
facility: Unidad Médica para la Salud Integral (UMSI)
state: Nuevo Leon
city: Culiacán
country: Mexico
facility: Hospital General de Culiacán
city: Zapopan
country: Mexico
facility: Hospital General de Occidente
Study officials:
affiliation: Veru Inc.
name: Barnette
role: STUDY_CHAIR
References: