A Phase 3 Randomized Double Blind Efficacy and Safety Study of Oral Polio Vaccine and NA-831 for Covid-19

Study Overview
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Brief Summary
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In this randomized double blind Phase 3 clinical trial we will study the efficacy and safety of oral polio vaccine with and without NA-831 versus placebo.

Detailed Description
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Early clinical studies showed that besides protecting against poliomyelitis, oral polio vaccine (OPV) reduced the number of other viruses that could be isolated from immunized children, compared with placebo recipients. Both poliovirus and coronavirus are positive-strand RNA viruses; therefore, it is likely that they may induce and be affected by common innate immunity mechanisms. Recent reports indicate that COVID-19 may result in suppressed innate immune responses. Stimulation by live attenuated oral polio vaccines could increase resistance to infection by the causal virus, severe acute respiratory syndrome-SARS-CoV-2. It has been discovered that SARS-CoV-2 viruses (Covid-19) can directly invade the nervous system of patients, instead of injuring the nervous system through the immune response. Increasing evidence suggests that infection with SARS-CoV-2 causes neurological deficits in a substantial proportion of affected patients. It was observed that patients surviving COVID-19 are at high risk for subsequent development of neurological disease and in particular Alzheimer's disease. NA-831 is a new neuroprotective and neurogenesis drug that has been demonstrated its promising safety and efficacy in Phase 2A for the treatment of early onset ofAlzheimer's disease. NA-831 in oral formulation is well tolerated NA-831 with no adverse effects. The Phase 3 clinical trial will evaluate the safety and efficacy of OPV with and without NA-831 versus placebo.

Official Title
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A Phase 3, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Polio Vaccine and NA-831 for Prophylaxis and Treatment of Early Onset of Covid-19

Conditions
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Covid19, SARS (Severe Acute Respiratory Syndrome), SARS-CoV Infection, SARS-CoV-2

Intervention / Treatment
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* Biological: Biological: oral polio vaccine
* Biological: Comparable Placebo
* Drug: NA-831
* Drug: Comparable Placebo of drug
* Combination Product: Combination of oral polio vaccine and NA-831
* Combination Product: Comparable Placebo of Oral Polio Vaccine and Placebo of drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are at high risk of SARS-CoV-2 infection, defined as adults whose locations or circumstances put them at appreciable risk of exposure to SARS-CoV-2 and COVID-19. Understands and agrees to comply with the study procedures and provides written informed consent. Able to comply with study procedures based on the assessment of the Investigator. Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for ≥12 consecutive months prior to Screening without an alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status. Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria: Has a negative pregnancy test at Screening and on the day of the first dose (Day 1). Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1). Has agreed to continue adequate contraception through 3 months following the second dose on Day 29. Is not currently breastfeeding. Male participants engaging in activity that could result in pregnancy of sexual partners must agree to practice adequate contraception and refrain from sperm donation from the time of the first dose and through 3 months after the second dose. Healthy adults or adults with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment. Exclusion Criteria: Is acutely ill or febrile 72 hours prior to or at Screening. Fever is defined as a body temperature ≥38.0°C/100.4°F. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator. Is pregnant or breastfeeding. Known history of SARS-CoV-2 infection. Prior administration of an investigational coronavirus (SARS-CoV, Middle East Respiratory Syndrome [MERS]-CoV) vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-19. Demonstrated inability to comply with the study procedures. An immediate family member or household member of this study's personnel. History of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine. Bleeding disorder considered a contraindication to intramuscular injection or phlebotomy. Has received or plans to receive a vaccine within 28 days prior to the first dose (Day 1) or plans to receive a non-study vaccine within 28 days prior to or after any dose of investigational product (except for seasonal influenza vaccine). Has participated in an interventional clinical study within 28 days prior to the day of enrollment. Immunosuppressive or immunodeficient state, including human immunodeficiency virus (HIV) infection, asplenia, and recurrent severe infections. Has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids ≥20 milligram (mg)/day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to Screening. Has received systemic immunoglobulins or blood products within 3 months prior to the day of Screening. Has donated ≥450 milliliters (mL) of blood products within 28 days prior to Screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard dose bivalent oral polio vaccine<br>Biological: oral polio vaccine Bivalent OPV (GSK), 0.1 ml administered orally on a sugar lump | Biological: Biological: oral polio vaccine<br>* Bivalent OPV (GSK), 0.1 ml administered orally on a sugar lump<br>* Other names: Oral Polio Vaccine (OPV);|
| Placebo Comparator: Comparable Placebo- 0.10 mg/kg<br>Saline administered orally on a sugar lump | Biological: Comparable Placebo<br>* Placebo of a vaccine 0.1 ml administered orally on a sugar lump<br>* Other names: Placebo comparator;|
| Experimental: Standard dose of NA-831<br>Drug: neuroprotection NA-831 30 mg of NA-831in a capsule administered orally | Drug: NA-831<br>* Drug: NA-831 30 mg of NA-831 in a capsule administered orally<br>* Other names: NA-81 is a neuroprotective drug;|
| Placebo Comparator: Comparable Placebo- 30mg<br>30 mg of placebo in a capsule administered orally | Drug: Comparable Placebo of drug<br>* Placebo 30 mg in a capsule administered orally<br>* Other names: Placebo comparator;|
| Experimental: Standard dose of bivalent OPV and NA-831<br>Biological: oral polio vaccine Bivalent OPV (GSK), 0.1 ml administered orally on a sugar lump Plus 30 mg of neuroprotection drug NA-831 in a capsule administered orally | Combination Product: Combination of oral polio vaccine and NA-831<br>* Combination of biological: Bivalent OPV (GSK), 0.1 ml administered orally on a sugar lump and drug NA-831 30 mg in a capsule administered orally<br>* Other names: OPV and Drug combination;|
| Placebo Comparator: Comparable Placebo<br>Placebo of a vaccine administered orally on a sugar lump Plus 30 mg of a placebo in a capsule administered orally | Combination Product: Comparable Placebo of Oral Polio Vaccine and Placebo of drug<br>* Combination of biological placebo 0.1 ml administered orally on a sugar lump and drug placebo 30 mg in a capsule administered orally<br>* Other names: Placebo Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose of OPV with or without NA-831 | Number of participants infected with Covid-19 after second dose | Time Frame: Day 29 (second dose) up to Day 365 (1 years after second dose) | 
| Number of Participants with Adverse Events (AEs) or Medically Attended AEs (MAAEs) Leading to Withdrawal | Number of participants with adverse events | Time Frame: Up to Day 365 (1 years after second dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of OPV with or without NA-831 | Clinical signs indicative of severe COVID-19 as predefined for the study. | Time Frame: Day 29 (second dose) up to Day 365 (1 years after second dose) | 
| Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of OPV with or without NA-831 or Placebo regardless of evidence of prior SARS-CoV-2 Infection | Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study. | Time Frame: Day 29 (second dose) up to Day 759 (2 years after second dose) |