<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04480333</url>
  </required_header>
  <id_info>
    <org_study_id>NEUROSIVIR</org_study_id>
    <nct_id>NCT04480333</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and NA-831</brief_title>
  <acronym>NEUROSIVIR</acronym>
  <official_title>A Randomized, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and in Combination With NA-831 in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NeuroActiva, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NeuroActiva, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The clinical study is designed to evaluate the safety, tolerability and pharmacokinetics of&#xD;
      inhaled nanoparticle nanoparticle formulation of Remdesivir (GS-5734) alone and in&#xD;
      combination with NA-831 in 48 healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It has been discovered that SARS-CoV-2 viruses (Covid-19) can directly invade the nervous&#xD;
      system of patients, instead of injuring the nervous system through the immune response.&#xD;
      Neurotropism is one common feature of Covid-19. Such neuro-invasive propensity of Covid-19&#xD;
      has been documented almost for all the Beta-coronaviruses including SARS-CoV and MERS-CoV.&#xD;
&#xD;
      Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a&#xD;
      substantial proportion of affected patients. It was observed that patients surviving COVID-19&#xD;
      are at high risk for subsequent development of neurological disease and in particular&#xD;
      Alzheimer's disease.&#xD;
&#xD;
      NA-831 is a new neuroprotective and neurogenesis drug that has been demonstrated its&#xD;
      promising safety and efficacy in Phase 2A for the treatment of early onset of Alzheimer's&#xD;
      disease. NA-831 in oral formulation is well tolerated NA-831 with no adverse effects. NA-831&#xD;
      in oral formulation exhibits predictable pharmacokinetics including dose-dependent exposure&#xD;
      linearity and low variability.&#xD;
&#xD;
      Based on animal studies, NA-831 can provide effective interventions during the severe acute&#xD;
      respiratory syndrome, and provide appropriate rehabilitation measures afterwards.&#xD;
&#xD;
      Remdesivir (GS-5734) intravenous formulation has been approved by the FDA under the emergency&#xD;
      use authorization for potential treatment of severe cases of Covid-19.&#xD;
&#xD;
      It was found the upper respiratory tract is the most prevalent site of SARS-CoV-2 infection&#xD;
      early in disease. Delivering drugs directly to the primary site of infection with a&#xD;
      nebulizer, inhaled nanoparticle formulation may enable more targeted and accessible&#xD;
      administration in non-hospitalized patients and potentially lower systemic exposure to the&#xD;
      drug.&#xD;
&#xD;
      The study is designed to evaluate the safety, tolerability and pharmacokinetics of a new&#xD;
      nanoparticle formulation of Remdesivir (GS-5734) and combination therapy with NA-831 in&#xD;
      healthy volunteers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">September 15, 2020</start_date>
  <completion_date type="Anticipated">March 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>The dose escalation given to healthy volunteers across the following cohorts:&#xD;
NA-831 cohorts:&#xD;
0.1 mg/kg NA-831, number of subjects N=2 and 2 subjects on placebos 0.2 mg/kg NA-831, number of subjects N=4 and 2 subjects on placebos 0.5 mg/kg NA-831, number of subjects N=4 and 2 subjects on placebos&#xD;
GS-5734 cohorts:&#xD;
mg/kg GS-5734, number of subjects N=2 and 2 subjects on placebos&#xD;
mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos&#xD;
4 mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos&#xD;
NA-831 plus GS-5734 cohorts:&#xD;
0.1 mg/kg NA-831 plus 1 mg/kg GS-5734, number of subjects N=2 and 2 subjects on placebos 0.2 mg/kg NA-831 plus 2 mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos 0.5 mg/kg NA-831 plus 4 mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Participants Experiencing any Treatment-Emergent Adverse Events</measure>
    <time_frame>First dose date up to Day 30 Follow-up Assessment</time_frame>
    <description>AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities</measure>
    <time_frame>First dose date up to Day 30 Follow-up Assessment</time_frame>
    <description>This will be assessed at various time points by clinical laboratory tests and vital signs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration (Cmax) - Pharmacokinetic Assessment</measure>
    <time_frame>7 days</time_frame>
    <description>Monitoring of the levels of drugs in subject sera at various time points to elucidate the maximum concentration (Cmax) of NA-831 and GS-5734 in human serum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment</measure>
    <time_frame>7 days</time_frame>
    <description>Monitoring of the levels of drugs in subject sera at various time points to elucidate the time to maximum concentration (Tmax) of NA-831 and GS-5734 in human serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment</measure>
    <time_frame>7 days</time_frame>
    <description>Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve from time of administration to the last measurable of NA-831 and GS-5734</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve Extrapolated to Infinity (AUC0-∞)</measure>
    <time_frame>7 days</time_frame>
    <description>Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve extrapolated to infinity (AUC0-∞) of NA-831 and GS-5734</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-Life (t1/2) - Pharmacokinetic Assessment</measure>
    <time_frame>7 days</time_frame>
    <description>Monitoring of the levels of drugs in subject sera at various time points to elucidate the half-life (t1/2) of NA-831 and GS-5734 in human serum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution (Vd) - Pharmacokinetic Assessment</measure>
    <time_frame>7 days</time_frame>
    <description>Monitoring of the levels of drugs in subject sera through various time points to elucidate the volume of distribution (Vd) of NA-831 and GS-5734 in human serum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance [CL] - Pharmacokinetic Assessment</measure>
    <time_frame>7 days</time_frame>
    <description>Monitoring of the levels of drugs in subject sera through at various time points to elucidate clearance [CL] of NA-831 and GS-5734 in human serum.</description>
  </secondary_outcome>
  <number_of_arms>12</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Covid19</condition>
  <condition>Corona Virus Infection</condition>
  <condition>Severe Acute Respiratory Syndrome</condition>
  <condition>Severe Acute Respiratory Infection</condition>
  <condition>Severe Acute Respiratory Syndrome (SARS) Pneumonia</condition>
  <condition>Severe Acute Respiratory Syndrome of Upper Respiratory Tract</condition>
  <condition>Neurodegeneration</condition>
  <condition>Neuroinflammatory Response</condition>
  <arm_group>
    <arm_group_label>Drug: NA-831 - 0.10 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 Subjects will take inhaled formulation of NA-831 once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparable Placebo- 0.10 mg/kg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 subjects will take inhaled formulation of placebo once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug: NA-831 - 0.20 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will take inhaled formulation of NA-831 once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparable Placebo- 0.20 mg/kg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 subjects will take inhaled formulation of placebo once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug: GS-5734 - 1.00 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparable Placebo- 1.00 mg.kg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug: GS-5734 - 2.00 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects will take inhaled formulation of GS-5734 once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparable Placebo - 2.00 mg/kg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 Subjects- will take inhaled formulation NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) once/day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 Subjects - inhaled formulation of placebo once/day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drugs: NA-831( 0.20 mg/kg) + GS-5734 (2.00 mg/kg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 Subjects- inhaled formulation of NA-831 (0.20 mg/kg) + GS-5734 (2.00 mg/kg) once/day for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo- 0.20 mg/kg + 2.00mg/kg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 Subjects- inhaled formulation of placebo once/day for 5 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug: NA-831 - 0.10 mg/kg</intervention_name>
    <description>NA-831 in nanoparticle inhalation formulation</description>
    <arm_group_label>Drug: NA-831 - 0.10 mg/kg</arm_group_label>
    <other_name>NA-831 is a neuroprotective and neurogenesis drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo- 0.10 mg/kg</intervention_name>
    <description>Placebo in nanoparticle inhalation formulation</description>
    <arm_group_label>Comparable Placebo- 0.10 mg/kg</arm_group_label>
    <other_name>Placebo Comparator</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug: NA-831 - 0.20 mg/kg</intervention_name>
    <description>NA-831 in nanoparticle inhalation formulation</description>
    <arm_group_label>Drug: NA-831 - 0.20 mg/kg</arm_group_label>
    <other_name>NA-81 is a neuroprotective drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo- 0.20 mg/kg</intervention_name>
    <description>Placebo in nanoparticle inhalation formulation</description>
    <arm_group_label>Comparable Placebo- 0.20 mg/kg</arm_group_label>
    <other_name>Placebo Comparator</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug: GS-5734 - 1.00 mg/kg</intervention_name>
    <description>GS-5734 in nanoparticle inhaled formulation</description>
    <arm_group_label>Drug: GS-5734 - 1.00 mg/kg</arm_group_label>
    <other_name>GS-5734 (Remdesivir) is an antiviral drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo- 1.00 mg/kg</intervention_name>
    <description>Placebo in nanoparticle inhalation formulation</description>
    <arm_group_label>Comparable Placebo- 1.00 mg.kg</arm_group_label>
    <other_name>Placebo Comparator</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug: GS-5734 - 2.00 mg/kg</intervention_name>
    <description>GS-5734 in nanoparticle inhaled formulation</description>
    <arm_group_label>Drug: GS-5734 - 2.00 mg/kg</arm_group_label>
    <other_name>GS-5734 (Remdesivir) is an anti-viral drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo- 2.00 mg/kg</intervention_name>
    <description>Placebo in nanoparticle inhaled formulation</description>
    <arm_group_label>Comparable Placebo - 2.00 mg/kg</arm_group_label>
    <other_name>Placebo Comparator</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)</intervention_name>
    <description>The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation</description>
    <arm_group_label>Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)</arm_group_label>
    <other_name>Combination therapy of NA-831 a neuroprotective drug and GS-5734 an antiviral drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Placebo 0.10 mg + 1.00 mg/kg</intervention_name>
    <description>The combined placebo are in nanoparticle inhaled formulation</description>
    <arm_group_label>Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg</arm_group_label>
    <other_name>Placebo Comparator</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)</intervention_name>
    <description>The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation</description>
    <arm_group_label>Drugs: NA-831( 0.20 mg/kg) + GS-5734 (2.00 mg/kg)</arm_group_label>
    <other_name>Combination therapy of NA-831, a neuroprotective drug and GS-5734, an antiviral drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Placebo 0.20 mg + 2.00 mg/kg</intervention_name>
    <description>Placebo 0.10 mg + 1.00 mg/kg</description>
    <arm_group_label>Placebo- 0.20 mg/kg + 2.00mg/kg</arm_group_label>
    <other_name>Placebo Comparator</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
          1. Healthy adult volunteers, aged 21 to 50 years old, men or women.&#xD;
&#xD;
          2. Subjects negative for human immunodeficiency virus (HIV antibody screen), Hepatitis B&#xD;
             virus surface Antigen (HBsAg) and Hepatitis C virus (HCV antibody screen).&#xD;
&#xD;
          3. Subjects who are willing to comply with the requirements of the study protocol, attend&#xD;
             scheduled visits and make themselves available for the duration of the study with&#xD;
             access to a consistent means of telephone contact.&#xD;
&#xD;
          4. Subjects who give written informed consent approved by the Internal Review Board&#xD;
             governing the site.&#xD;
&#xD;
          5. Satisfactory baseline medical assessment as assessed by physical examination and a&#xD;
             stable health status. Normal laboratory values must be within normal range of the&#xD;
             assessing site or show minor variations that are deemed not clinically significant as&#xD;
             judged by the Investigator and acceptable for study entry.&#xD;
&#xD;
          6. Accessible vein in the forearm for blood collection.&#xD;
&#xD;
          7. Female subjects of childbearing potential may be enrolled in the study if they have&#xD;
             negative urine pregnancy tests on the day of screening and day of admission.&#xD;
&#xD;
          8. Female subjects of non-childbearing potential due to surgical sterilization&#xD;
             (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause.&#xD;
&#xD;
          9. Both male (if he has a partner of childbearing potential) and female subjects (of&#xD;
             childbearing potential) must agree to use adequate and reliable contraceptive measures&#xD;
             (e.g. spermicides, condoms, contraceptive pills, etc.) or practice abstinence&#xD;
             throughout the duration of the study (up to 30 days post-dosing).&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Subject previously diagnosed with COVID-19 or had been issued with a quarantine order&#xD;
             by the Center of Disease Control (CDC).&#xD;
&#xD;
          2. Presence of acute infection in the preceding 14 days, or presence of a temperature ≥&#xD;
             100.0 ˚F (oral or tympanic temperature assessment), or acute symptoms of any severity&#xD;
             on the scheduled date of admission.&#xD;
&#xD;
          3. History of severe drug and / or food allergies and / or known allergies to the trial&#xD;
             product or its components.&#xD;
&#xD;
          4. Female subject who is pregnant or breast-feeding.&#xD;
&#xD;
          5. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,&#xD;
             , or immunosuppressive disorders.&#xD;
&#xD;
          6. Any neurological disease or history of significant neurological disorder (e.g.&#xD;
             meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré&#xD;
             syndrome [genetic/congenital or acquired]).&#xD;
&#xD;
          7. Evidence of clinically significant anemia (HB &lt; 10 g/dL) or any other significant&#xD;
             active hematological disease, or having donated &gt; 450 mL of blood within the past&#xD;
             three (3) months.&#xD;
&#xD;
          8. Participation or planned participation in a study involving the administration of an&#xD;
             investigational compound within the past four (4) months or during this study period.&#xD;
&#xD;
          9. Receipt of immunoglobulins and/or any blood products within nine (9) months of study&#xD;
             enrolment or planned administration of any of these products during the study period.&#xD;
&#xD;
         10. Evidence of Hepatitis B or C or HIV by laboratory testing.&#xD;
&#xD;
         11. A positive test result for drugs of abuse (except a positive test result associated&#xD;
             with prescription medication that has been reviewed and approved by the investigator)&#xD;
             or alcohol at screening.&#xD;
&#xD;
         12. Administration of any licensed vaccine within 30 days before the first study vaccine&#xD;
             dose.&#xD;
&#xD;
         13. Both male (if he has a partner of childbearing potential) and female subjects (of&#xD;
             childbearing potential) who are unwilling to use adequate contraception or practice&#xD;
             abstinence throughout the duration of the study (up to 84 days post-dosing).&#xD;
&#xD;
         14. Any condition that, in the opinion of the Investigator, would complicate or compromise&#xD;
             the study or well-being of the subject.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lloyd Tran, PhD</last_name>
    <role>Study Director</role>
    <affiliation>NeuroActiva, Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Brian Tran, MD</last_name>
    <phone>1-415-941-3133</phone>
    <email>BTran@neuroactiva.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Markku Kurkinen, PhD</last_name>
    <phone>1-415-941-3133</phone>
    <email>MKurkinen@neuroactiva.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Coronavirus Research Institute</name>
      <address>
        <city>Sunnyvale</city>
        <state>California</state>
        <zip>94086</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Nguyen, MD</last_name>
      <email>research@covri.org</email>
    </contact>
    <contact_backup>
      <last_name>Lloyd Tran, PhD</last_name>
      <email>LTran@neuroactiva.com</email>
    </contact_backup>
    <investigator>
      <last_name>Markku Kurkinen, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>July 16, 2020</last_update_submitted>
  <last_update_submitted_qc>July 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Covid-19</keyword>
  <keyword>Corona Virus Infection</keyword>
  <keyword>Severe Acute Respiratory Syndrome</keyword>
  <keyword>Severe Acute Respiratory Infection</keyword>
  <keyword>Severe Acute Respiratory Syndrome (SARS) Pneumonia</keyword>
  <keyword>Severe Acute Respiratory Syndrome of Upper Respiratory Tract</keyword>
  <keyword>Neurodegeneration</keyword>
  <keyword>Neuroinflammation</keyword>
  <keyword>Cognitive decline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Respiratory Tract Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Nerve Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antiviral Agents</mesh_term>
    <mesh_term>Remdesivir</mesh_term>
    <mesh_term>Neuroprotective Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We plan to share the Study Protocol</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>90 days after the completion of the study</ipd_time_frame>
    <ipd_access_criteria>to be determined</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04480333
org study id: NEUROSIVIR
nct id: NCT04480333
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The clinical study is designed to evaluate the safety, tolerability and pharmacokinetics of
      inhaled nanoparticle nanoparticle formulation of Remdesivir (GS-5734) alone and in
      combination with NA-831 in 48 healthy volunteers.
It has been discovered that SARS-CoV-2 viruses (Covid-19) can directly invade the nervous
      system of patients, instead of injuring the nervous system through the immune response.
      Neurotropism is one common feature of Covid-19. Such neuro-invasive propensity of Covid-19
      has been documented almost for all the Beta-coronaviruses including SARS-CoV and MERS-CoV.

      Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a
      substantial proportion of affected patients. It was observed that patients surviving COVID-19
      are at high risk for subsequent development of neurological disease and in particular
      Alzheimer's disease.

      NA-831 is a new neuroprotective and neurogenesis drug that has been demonstrated its
      promising safety and efficacy in Phase 2A for the treatment of early onset of Alzheimer's
      disease. NA-831 in oral formulation is well tolerated NA-831 with no adverse effects. NA-831
      in oral formulation exhibits predictable pharmacokinetics including dose-dependent exposure
      linearity and low variability.

      Based on animal studies, NA-831 can provide effective interventions during the severe acute
      respiratory syndrome, and provide appropriate rehabilitation measures afterwards.

      Remdesivir (GS-5734) intravenous formulation has been approved by the FDA under the emergency
      use authorization for potential treatment of severe cases of Covid-19.

      It was found the upper respiratory tract is the most prevalent site of SARS-CoV-2 infection
      early in disease. Delivering drugs directly to the primary site of infection with a
      nebulizer, inhaled nanoparticle formulation may enable more targeted and accessible
      administration in non-hospitalized patients and potentially lower systemic exposure to the
      drug.

      The study is designed to evaluate the safety, tolerability and pharmacokinetics of a new
      nanoparticle formulation of Remdesivir (GS-5734) and combination therapy with NA-831 in
      healthy volunteers.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The dose escalation given to healthy volunteers across the following cohorts:
NA-831 cohorts:
0.1 mg/kg NA-831, number of subjects N=2 and 2 subjects on placebos 0.2 mg/kg NA-831, number of subjects N=4 and 2 subjects on placebos 0.5 mg/kg NA-831, number of subjects N=4 and 2 subjects on placebos
GS-5734 cohorts:
mg/kg GS-5734, number of subjects N=2 and 2 subjects on placebos
mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos
4 mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos
NA-831 plus GS-5734 cohorts:
0.1 mg/kg NA-831 plus 1 mg/kg GS-5734, number of subjects N=2 and 2 subjects on placebos 0.2 mg/kg NA-831 plus 2 mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos 0.5 mg/kg NA-831 plus 4 mg/kg GS-5734, number of subjects N=4 and 2 subjects on placebos.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events
time frame: First dose date up to Day 30 Follow-up Assessment
description: AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0
measure: Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities
time frame: First dose date up to Day 30 Follow-up Assessment
description: This will be assessed at various time points by clinical laboratory tests and vital signs.
measure: Maximum Concentration (Cmax) - Pharmacokinetic Assessment
time frame: 7 days
description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the maximum concentration (Cmax) of NA-831 and GS-5734 in human serum.
measure: Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment
time frame: 7 days
description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the time to maximum concentration (Tmax) of NA-831 and GS-5734 in human serum
measure: AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment
time frame: 7 days
description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve from time of administration to the last measurable of NA-831 and GS-5734
measure: Area Under the Curve Extrapolated to Infinity (AUC0-∞)
time frame: 7 days
description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve extrapolated to infinity (AUC0-∞) of NA-831 and GS-5734
measure: Half-Life (t1/2) - Pharmacokinetic Assessment
time frame: 7 days
description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the half-life (t1/2) of NA-831 and GS-5734 in human serum.
measure: Volume of Distribution (Vd) - Pharmacokinetic Assessment
time frame: 7 days
description: Monitoring of the levels of drugs in subject sera through various time points to elucidate the volume of distribution (Vd) of NA-831 and GS-5734 in human serum.
measure: Clearance [CL] - Pharmacokinetic Assessment
time frame: 7 days
description: Monitoring of the levels of drugs in subject sera through at various time points to elucidate clearance [CL] of NA-831 and GS-5734 in human serum.
arm group label: Drug: NA-831 - 0.10 mg/kg
arm group type: Experimental
description: 3 Subjects will take inhaled formulation of NA-831 once a day for 5 days
arm group label: Comparable Placebo- 0.10 mg/kg
arm group type: Placebo Comparator
description: 3 subjects will take inhaled formulation of placebo once a day for 5 days
arm group label: Drug: NA-831 - 0.20 mg/kg
arm group type: Experimental
description: 6 Subjects will take inhaled formulation of NA-831 once a day for 5 days
arm group label: Comparable Placebo- 0.20 mg/kg
arm group type: Placebo Comparator
description: 3 subjects will take inhaled formulation of placebo once a day for 5 days
arm group label: Drug: GS-5734 - 1.00 mg/kg
arm group type: Experimental
description: 3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
arm group label: Comparable Placebo- 1.00 mg.kg
arm group type: Placebo Comparator
description: 3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
arm group label: Drug: GS-5734 - 2.00 mg/kg
arm group type: Experimental
description: 6 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
arm group label: Comparable Placebo - 2.00 mg/kg
arm group type: Placebo Comparator
description: 3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
arm group label: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
arm group type: Experimental
description: 3 Subjects- will take inhaled formulation NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) once/day for 5 days
arm group label: Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg
arm group type: Placebo Comparator
description: 3 Subjects - inhaled formulation of placebo once/day for 5 days
arm group label: Drugs: NA-831( 0.20 mg/kg) + GS-5734 (2.00 mg/kg)
arm group type: Experimental
description: 6 Subjects- inhaled formulation of NA-831 (0.20 mg/kg) + GS-5734 (2.00 mg/kg) once/day for 5 days
arm group label: Placebo- 0.20 mg/kg + 2.00mg/kg
arm group type: Placebo Comparator
description: 3 Subjects- inhaled formulation of placebo once/day for 5 days
intervention type: Drug
intervention name: Drug: NA-831 - 0.10 mg/kg
description: NA-831 in nanoparticle inhalation formulation
arm group label: Drug: NA-831 - 0.10 mg/kg
other name: NA-831 is a neuroprotective and neurogenesis drug
intervention type: Drug
intervention name: Placebo- 0.10 mg/kg
description: Placebo in nanoparticle inhalation formulation
arm group label: Comparable Placebo- 0.10 mg/kg
other name: Placebo Comparator
intervention type: Drug
intervention name: Drug: NA-831 - 0.20 mg/kg
description: NA-831 in nanoparticle inhalation formulation
arm group label: Drug: NA-831 - 0.20 mg/kg
other name: NA-81 is a neuroprotective drug
intervention type: Drug
intervention name: Placebo- 0.20 mg/kg
description: Placebo in nanoparticle inhalation formulation
arm group label: Comparable Placebo- 0.20 mg/kg
other name: Placebo Comparator
intervention type: Drug
intervention name: Drug: GS-5734 - 1.00 mg/kg
description: GS-5734 in nanoparticle inhaled formulation
arm group label: Drug: GS-5734 - 1.00 mg/kg
other name: GS-5734 (Remdesivir) is an antiviral drug
intervention type: Drug
intervention name: Placebo- 1.00 mg/kg
description: Placebo in nanoparticle inhalation formulation
arm group label: Comparable Placebo- 1.00 mg.kg
other name: Placebo Comparator
intervention type: Drug
intervention name: Drug: GS-5734 - 2.00 mg/kg
description: GS-5734 in nanoparticle inhaled formulation
arm group label: Drug: GS-5734 - 2.00 mg/kg
other name: GS-5734 (Remdesivir) is an anti-viral drug
intervention type: Drug
intervention name: Placebo- 2.00 mg/kg
description: Placebo in nanoparticle inhaled formulation
arm group label: Comparable Placebo - 2.00 mg/kg
other name: Placebo Comparator
intervention type: Combination Product
intervention name: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
description: The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation
arm group label: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
other name: Combination therapy of NA-831 a neuroprotective drug and GS-5734 an antiviral drug
intervention type: Combination Product
intervention name: Placebo 0.10 mg + 1.00 mg/kg
description: The combined placebo are in nanoparticle inhaled formulation
arm group label: Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg
other name: Placebo Comparator
intervention type: Combination Product
intervention name: Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)
description: The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation
arm group label: Drugs: NA-831( 0.20 mg/kg) + GS-5734 (2.00 mg/kg)
other name: Combination therapy of NA-831, a neuroprotective drug and GS-5734, an antiviral drug
intervention type: Combination Product
intervention name: Placebo 0.20 mg + 2.00 mg/kg
description: Placebo 0.10 mg + 1.00 mg/kg
arm group label: Placebo- 0.20 mg/kg + 2.00mg/kg
other name: Placebo Comparator
criteria: 
gender: All
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: No
last name: Lloyd Tran, PhD
role: Study Director
affiliation: NeuroActiva, Inc.
last name: Brian Tran, MD
phone: 1-415-941-3133
email: BTran@neuroactiva.com
last name: Markku Kurkinen, PhD
phone: 1-415-941-3133
email: MKurkinen@neuroactiva.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Virus Diseases
mesh term: Respiratory Tract Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Coronavirus Infections
mesh term: Syndrome
mesh term: Nerve Degeneration
mesh term: Antiviral Agents
mesh term: Remdesivir
mesh term: Neuroprotective Agents
sharing ipd: Yes
ipd description: We plan to share the Study Protocol
ipd info type: Study Protocol
ipd time frame: 90 days after the completion of the study
ipd access criteria: to be determined