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

NeuroActiva

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Severe Acute Respiratory Syndrome Coronavirus 2; Severe Acute Respiratory Infection; Coronavirus Infection

Treatments: Drug: Drug: NA-831; Combination Product: NA-831and Dexamethasone; Combination Product: NA-831 and Atazanavir; Combination Product: Atazanavir and Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT04452565

NATADEX

Details and patient eligibility

About

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.

Full 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.

Enrollment: 525 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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525 participants in 4 patient groups

Active Comparator: NA-831 alone

Active Comparator group

Description:

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

Treatment:

Drug: Drug: NA-831

Active Comparator: NA-831 plus Atazanavir Sulfate

Active Comparator group

Description:

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.

Treatment:

Combination Product: NA-831 and Atazanavir

Active Comparator: NA-83 plus Dexamethasone

Active Comparator group

Description:

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.

Treatment:

Combination Product: NA-831and Dexamethasone

Active Comparator: Atazanavir and Dexamethasone

Active Comparator group

Description:

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.

Treatment:

Combination Product: Atazanavir and Dexamethasone