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

Phase 2

• Conditions: Severe Acute Respiratory Infection; Coronavirus Infection; Severe Acute Respiratory Syndrome Coronavirus 2
• Interventions: Combination Product: NA-831 and Atazanavir; Combination Product: NA-831and Dexamethasone; Combination Product: Atazanavir and Dexamethasone

• Registration Number: NCT04452565
• Lead Sponsor: Biomed Industries, Inc.

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.

Study Timeline

• Study First Submitted: 2020-06-26
• Study First Submitted QC: 2020-06-26
• Study First Posted: 2020-06-30
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-31
• Last Update Posted: 2022-02-16
• Study Start: 2022-06-15
• Primary Completion: 2023-12-15
• Study Completion: 2023-12-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 525

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Comparator: NA-831 plus Atazanavir Sulfate	NA-831 and Atazanavir	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.
Active Comparator: NA-83 plus Dexamethasone	NA-831and Dexamethasone	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.
Active Comparator: Atazanavir and Dexamethasone	Atazanavir and Dexamethasone	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.

Primary Outcome Measures

Name	Time	Method
1. Time (Hours) to recovery	[ Time Frame: 36 days ]	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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Coronavirus Research Institute; 🇺🇸 Orange, California, United States

Coronavirus Research Institute- Testing Site; 🇺🇸 Fort Sam Houston, Texas, United States

Coronavirus Research Institute-Testing Site; 🇺🇸 Tacoma, Washington, United States

Coronavirus Research Institute-Testing Site-; 🇺🇸 Bronx, New York, United States

Coronavirus Research Testing Site; 🇺🇸 San Francisco, California, United States