Respiratory Distress Syndrome, Adult
Conditions
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).
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.
Interventions
DRUGVeru-111
Respiratory Distress Syndrome, Adult
Sponsors
Veru Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind Randomized Placebo-Controlled
Intervention model description
Randomized Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Day 15, Day 22 and Day 29 | 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. |
| Proportion of Subjects Alive and Discharged From Hospital by Visit | Day 15, Day 22 and Day 29 | 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). |
| Patients Alive and Free of Respiratory Failure | Day 15 and Day 22 | Proportion of patients alive and free or respiratory failure |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Number of Patients Exposed to Veru-111 18 mg Veru-111 18mg capsules
Veru-111: Respiratory Distress Syndrome, Adult | 19 |
| Number of Patients Exposed to Placebo Placebo capsules
Veru-111: Respiratory Distress Syndrome, Adult | 20 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 2 |
Baseline characteristics
| Characteristic | Number of Patients Exposed to Veru-111 18 mg | Total | Number of Patients Exposed to Placebo |
|---|---|---|---|
| Age, Continuous | 59.3 Years STANDARD_DEVIATION 11.4 | 58.5 Years STANDARD_DEVIATION 12.28 | 57.8 Years STANDARD_DEVIATION 13.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 14 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 25 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 35 Participants | 16 Participants |
| Region of Enrollment United States | 19 participants | 39 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 3 Participants |
| Sex: Female, Male Male | 10 Participants | 27 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 19 | 5 / 20 |
| other Total, other adverse events | 12 / 19 | 12 / 20 |
| serious Total, serious adverse events | 3 / 19 | 5 / 20 |
Outcome results
Primary
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
Time frame: Day 29
Population: Responders
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Veru-111 18 mg | Number of Subjects That Are Alive Without Respiratory Failure at Day 29. | 17 Participants |
| Placebo | Number of Subjects That Are Alive Without Respiratory Failure at Day 29. | 14 Participants |
Secondary
Patients Alive and Free of Respiratory Failure
Proportion of patients alive and free or respiratory failure
Time frame: Day 15 and Day 22
Population: Responders
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Veru-111 18 mg | Patients Alive and Free of Respiratory Failure | Day 22 | 16 Participants |
| Veru-111 18 mg | Patients Alive and Free of Respiratory Failure | Day 15 | 16 Participants |
| Placebo | Patients Alive and Free of Respiratory Failure | Day 15 | 13 Participants |
| Placebo | Patients Alive and Free of Respiratory Failure | Day 22 | 14 Participants |
Secondary
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).
Time frame: Day 15, Day 22 and Day 29
Population: Responders - subjects who are alive and have been discharged from the hospital at the time of the visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Veru-111 18 mg | Proportion of Subjects Alive and Discharged From Hospital by Visit | Day 15 | 14 Participants |
| Veru-111 18 mg | Proportion of Subjects Alive and Discharged From Hospital by Visit | Day 22 | 17 Participants |
| Veru-111 18 mg | Proportion of Subjects Alive and Discharged From Hospital by Visit | Day 29 | 18 Participants |
| Placebo | Proportion of Subjects Alive and Discharged From Hospital by Visit | Day 15 | 12 Participants |
| Placebo | Proportion of Subjects Alive and Discharged From Hospital by Visit | Day 22 | 15 Participants |
| Placebo | Proportion of Subjects Alive and Discharged From Hospital by Visit | Day 29 | 14 Participants |
Secondary
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.
Time frame: Day 15, Day 22 and Day 29
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Veru-111 18 mg | Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Day 15 | 14 Participants |
| Veru-111 18 mg | Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Day 22 | 17 Participants |
| Veru-111 18 mg | Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Day 29 | 17 Participants |
| Placebo | Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Day 15 | 12 Participants |
| Placebo | Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Day 22 | 16 Participants |
| Placebo | Proportion of Subjects With Fever Normalization and SPO2 Greater Than 94% by Visit | Day 29 | 14 Participants |
Secondary
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
Time frame: Day 29
Population: World Health Organization Ordinal Scale for clinical improvement (Eight Point Ordinal Scale)-With Last Observation Carried Forward Values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Veru-111 18 mg | World Health Organization Ordinal Scale Clinical Improvement | -1.7 Units on WHO COVID Scale | Standard Deviation 1.49 |
| Placebo | World Health Organization Ordinal Scale Clinical Improvement | -1.1 Units on WHO COVID Scale | Standard Deviation 2.42 |