Clinical trial NCT04452565: NA-831, Atazanavir and Dexamethasone Combination Therapy for the Treatment of COVID-19 Infection
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Coronavirus Infection
Severe Acute Respiratory Infection
Severe Acute Respiratory Syndrome Coronavirus 2
Keywords: NA-831
Atazanavir
Dexamethasone
COVID-19
Coronavirus Infection
Severe Acute Respiratory Syndrome
Lead sponsor: Biomed Industries, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-30
Enrollment: 525
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: 1. Time (Hours) to recovery
timeFrame: [ Time Frame: 36 days ]
Secondary outcomes:
measure: Time fever resolution
timeFrame: [ Time Frame: 36 days ]
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Coronavirus Research Institute- Testing Site
state: California
city: Orange
country: United States
facility: Coronavirus Research Institute
state: California
city: Palo Alto
country: United States
facility: Coronavirus Research Institute-Testing Site
state: California
city: Sacramento
country: United States
facility: Coronavirus Research Institute-Testing Site
state: California
city: San Diego
country: United States
facility: Coronavirus Research Institute-Testing Site
state: California
city: San Francisco
country: United States
facility: Coronavirus Research Testing Site
state: California
city: Sunnyvale
country: United States
facility: Coronavirus Research Institute-Testing Site
state: California
city: Washington
country: United States
facility: Coronavirus Research Institute-Testing Site
state: District of Columbia
city: Washington
country: United States
facility: Coronavirus Research Institute-Testing Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Florida
city: Tampa
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Florida
city: Chicago
country: United States
facility: Coronavirus Research Institute- Testing Site
state: Illinois
city: Naperville
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Illinois
city: Baltimore
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Maryland
city: Bethesda
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Maryland
city: Boston
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Massachusetts
city: Worcester
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Michigan
city: Detroit
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Michigan
city: Newark
country: United States
facility: Coronavirus Research Institute-Testing Site
state: New Jersey
city: Bronx
country: United States
facility: Coronavirus Research Institute-Testing Site-
state: New York
city: New York
country: United States
facility: Coronavirus Research Institute-Testing Site
state: New York
city: Rochester
country: United States
facility: Coronavirus Research Institute- Testing Site
state: New York
city: Durham
country: United States
facility: Coronavirus Research Institute-Testing Site
state: North Carolina
city: Philadelphia
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Pennsylvania
city: Fort Sam Houston
country: United States
facility: Coronavirus Research Institute- Testing Site
state: Texas
city: Galveston
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Texas
city: Houston
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Texas
city: Kirkland
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Washington
city: Seattle
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Washington
city: Tacoma
country: United States
facility: Coronavirus Research Institute-Testing Site
state: Washington
Study officials:
affiliation: Biomed Industries, Inc.
name: Lloyd Tran, PhD
role: STUDY_DIRECTOR
References: