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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Coronavirus Infection; Severe Acute Respiratory Syndrome Coronavirus 2; Severe Acute Respiratory Infection
• Intervention / Treatment: Drug: Drug: NA-831; Combination product: NA-831 and Atazanavir; Combination product: NA-831and Dexamethasone; Combination product: Atazanavir and 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 Type: Interventional
• Enrollment (Anticipated): 525
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Brian Tran, MD; Phone Number: 800-824-5135; Email: BTran@biomedind.com
• Study Contact Backup: Name: Frank Kennedy, PhD; Phone Number: 800-824-5135; Email: FKennedy@biomedind.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Coronavirus Research Institute- Testing Site
    • Orange, California, United States, 92868
      • Recruiting
      • Coronavirus Research Institute
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Sacramento, California, United States, 95817
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • San Diego, California, United States, 92314
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • San Francisco, California, United States, 94110
      • Recruiting
      • Coronavirus Research Testing Site
    • Sunnyvale, California, United States, 94086
      • Recruiting
      • Coronavirus Research Institute-Testing Site
      • Contact: Lloyd Tran, PhD; Phone Number: 800-82405135; Email: LTran@biomedind.com
      • Contact: Markku Kurkinen, PhD; Phone Number: 800-824-5135; Email: MKurkinen@biomedind.com
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Washington, District of Columbia, United States, 20010
      • Not yet recruiting
      • Coronavirus Research Institute-Testing Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Tampa, Florida, United States, 33620
      • Recruiting
      • Coronavirus Research Institute-Testing Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Coronavirus Research Institute- Testing Site
    • Naperville, Illinois, United States, 60540
      • Not yet recruiting
      • Coronavirus Research Institute-Testing Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • Coronavirus Research Institute-Testing Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Worcester, Massachusetts, United States, 01655
      • Not yet recruiting
      • Coronavirus Research Institute-Testing Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Not yet recruiting
      • Coronavirus Research Institute-Testing Site
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Coronavirus Research Institute-Testing Site
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Recruiting
      • Coronavirus Research Institute-Testing Site
  • New York
    • Bronx, New York, United States, 10467
      • Recruiting
      • Coronavirus Research Institute-Testing Site-
    • New York, New York, United States, 10016
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Rochester, New York, United States, 14642
      • Not yet recruiting
      • Coronavirus Research Institute- Testing Site
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Recruiting
      • Coronavirus Research Institute-Testing Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Coronavirus Research Institute-Testing Site
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • Recruiting
      • Coronavirus Research Institute- Testing Site
    • Galveston, Texas, United States, 77555
      • Not yet recruiting
      • Coronavirus Research Institute-Testing Site
    • Houston, Texas, United States, 77030
      • Recruiting
      • Coronavirus Research Institute-Testing Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Coronavirus Research Institute-Testing Site
    • Tacoma, Washington, United States, 98431
      • Recruiting
      • Coronavirus Research Institute-Testing Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Comparator: NA-831 alone; 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; NA-831 is a neuroprotective drug, available at 30 mg capsule
Active Comparator: Active Comparator: NA-831 plus Atazanavir Sulfate; 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; Drug: NA-831 Neuroprotective drug Other Name: Traneurocin 30 mg capsule Drug: Atazanavir Sulfate Antiviral drug Other Name: Atazanavir Sulfate 200 mg tablet; Other Names: and Atazanavir
Active Comparator: Active Comparator: NA-83 plus 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.	Combination product: NA-831and Dexamethasone; Drug: NA-831 Neuroprotective drug Other Name: Traneurocin 30 mg capsule Drug: Dexamethasone anti-inflammatory drug Other Name: Dexamethasone 4 mg; Other Names: Dexamethasone
Active Comparator: Active Comparator: 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.	Combination product: Atazanavir and Dexamethasone; Drug: Atazanavir Sulfate Antiviral drug Other Name: Atazanavir Sulfate 200 mg tablet Drug: Dexamethasone anti-inflammatory drug Other Name: Dexamethasone 4 mg; 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 ]

Collaborators and Investigators

• Sponsor: NeuroActiva, Inc.
• Collaborators: Biomed Industries, Inc.
• Investigators: Study Director: Lloyd Tran, PhD, Biomed Industries, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 15, 2022
• Primary Completion (Anticipated): December 15, 2023
• Study Completion (Anticipated): December 15, 2023

Study Registration Dates

• First Submitted: June 26, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Dexamethasone; Atazanavir; Coronavirus Infection; Severe Acute Respiratory Syndrome; NA-831
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Infections; Communicable Diseases; Respiratory Tract Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Atazanavir Sulfate
• Other Study ID Numbers: NATADEX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No