NA-831, Atazanavir and Dexamethasone Combination Therapy for the Treatment of COVID-19 Infection

Study Overview
=================
Brief Summary
-----------------
This Phase 2/3 trial evaluates four treatment strategies for non-critically ill hospitalized participants (not requiring ICU admission and/or mechanical ventilation) with SARS CoV-2 infection, in which participants will receive NA-831 or Atazanavir with or without Dexamethasone.

Detailed Description
-----------------
The clinical Phase 2/3 evaluates the safety and efficacy of NA-831 alone, and a combination therapy comprises NA-831 with an anti-viral drug Atazanavir, NA-831 with an anti-inflammatory drug, Dexamethasone and a potential synergy between Atazanavir and Dexamethasone. NA-831 is also known as Traneurocin is a neuroprotective drug that is in clinical study for the treatment of Alzheimer's Disease. Participants will receive NA-831 or Atazanavir with or without Dexamethasone. Investigators are primarily interested in the time to recovery. In addition to study medications there will be daily symptom surveys for 14 days, then weekly thereafter for 3 weeks resulting in a total duration of follow up of 36 days. During hospitalization, daily symptom surveys will be carried out in conjunction with the study coordinators. Upon discharge participants will have the option to complete electronic symptom surveys or complete symptom surveys via telephone with the study coordinator. If electronic symptom surveys are selected on discharge participants will also receive a follow-up call from a study coordination every 7 days during the initial 14 day period. In addition, failure to submit a symptom survey will prompt a study follow up call.

Official Title
-----------------
Randomized Controlled Phase 2/3 Clinical Trial of NA-831 Alone or With Atazanavir, or NA-831 With Dexamethasone, or Atazanavir With Dexamethasone in the Treatment of COVID-19 Infection

Conditions
-----------------
Coronavirus Infection, Severe Acute Respiratory Infection, Severe Acute Respiratory Syndrome Coronavirus 2

Intervention / Treatment
-----------------
* Drug: Drug: NA-831
* Combination Product: NA-831 and Atazanavir
* Combination Product: NA-831and Dexamethasone
* Combination Product: Atazanavir and Dexamethasone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hospitalization for management of SARS CoV-2 infection Positive SARS CoV-2 test Age > = 18 years Provision of informed consent Electrocardiogram (ECG) ≤ 48 hours prior to enrollment Complete blood count, glucose-6 phosphate-dehydrogenase (G6PD), comprehensive metabolic panel and magnesium ≤ 48 hours prior to enrollment from standard of care. If participating in sexual activity that could lead to pregnancy, individuals of reproductive potential who can become pregnant must agree to use contraception throughout the study. At least one of the following must be used throughout the study: Condom (male or female) with or without spermicide Diaphragm or cervical cap with spermicide Intrauterine device (IUD) Hormone-based contraceptive Exclusion Criteria: Contraindication or allergy to NA-831, Atazanavir, Dexamethasone Current use any antiviral drug or anti-inflammatory drug Concurrent use of another investigational agent Invasive mechanical ventilation Participants who have any severe and/or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction, cardiac arrhythmias or know prolonged QTc > 470 males, > 480 female on ECG pulmonary insufficiency, epilepsy (interaction with chloroquine), Prior retinal eye disease Concurrent malignancy requiring chemotherapy Known Chronic Kidney disease, eGFR < 10 or dialysis G-6-PD deficiency, if unknown requires G6PD testing prior to enrollment Known Porphyria Known myasthenia gravis Currently pregnant or planning on getting pregnant while on study Breast feeding AST/ALT > five times the upper limit of normal ULN Bilirubin > five times the ULN Magnesium < 1.4 mEq/L Calcium < 8.4 mg/dL > 10.6 mg/dL Potassium < 3.3 > 5.5 mEg/L

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: NA-831 alone<br>Arm 1: NA-831 30 mg orally twice a day for one day, followed by 30 mg once day for four consecutive days (Five days in total). The drug will be supplied in 30 mg capsule | Drug: Drug: NA-831<br>* NA-831 is a neuroprotective drug, available at 30 mg capsule<br>|
| Active Comparator: Active Comparator: NA-831 plus Atazanavir Sulfate<br>Arm 2: NA-831 60 mg orally twice a day for one day, followed by 30 mg once a day for four consecutive days (Five days in total). The drug will be supplied in 30 mg capsule. AND Atazanavir 400 mg orally twice a day for one day, followed by 200 mg daily for four consecutive days (five days total). The drug will be supplied in 200 mg tablets. | Combination Product: NA-831 and Atazanavir<br>* Drug: NA-831 Neuroprotective drug Other Name: Traneurocin 30 mg capsule Drug: Atazanavir Sulfate Antiviral drug Other Name: Atazanavir Sulfate 200 mg tablet<br>* Other names: and Atazanavir;|
| Active Comparator: Active Comparator: NA-83 plus Dexamethasone<br>Active Comparator: NA-831 30 mg capsule plus Dexamethasone 4 mg Arm 3: NA-831 60 mg orally twice a day for one day, followed by 30 mg once a day for four consecutive days (Five days in total). The drug will be supplied in 30 mg capsule. AND Dexamethasone 8 mg orally twice a day for one day, followed by 4 mg daily for four consecutive days (five days total). The drug will be supplied in 4 mg tablets. | Combination Product: NA-831and Dexamethasone<br>* Drug: NA-831 Neuroprotective drug Other Name: Traneurocin 30 mg capsule Drug: Dexamethasone anti-inflammatory drug Other Name: Dexamethasone 4 mg<br>* Other names: Dexamethasone;|
| Active Comparator: Active Comparator: Atazanavir and Dexamethasone<br>Atazanavir 400 mg orally twice a day for one day, followed by 200 mg daily for four consecutive days (five days total). The drug will be supplied in 200 mg tablets. AND Dexamethasone 8 mg orally twice a day for one day, followed by 4 mg daily for four consecutive days (five days total). The drug will be supplied in 4 mg tablets. | Combination Product: Atazanavir and Dexamethasone<br>* Drug: Atazanavir Sulfate Antiviral drug Other Name: Atazanavir Sulfate 200 mg tablet Drug: Dexamethasone anti-inflammatory drug Other Name: Dexamethasone 4 mg<br>* Other names: Dexamethasone;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Time (Hours) to recovery | Time (hours) from randomization to recovery defined as 1) absence of fever, as defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications AND 2) absence of symptoms of greater than mild severity for 24 hours AND 3) not requiring supplemental oxygen beyond pre-COVID baseline AND 4) freedom from mechanical ventilation or death | [ Time Frame: 36 days ] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time fever resolution | Time to resolution of fever defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications | [ Time Frame: 36 days ] | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NA-831, Atazanavir, Dexamethasone, COVID-19, Coronavirus Infection, Severe Acute Respiratory Syndrome