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.
Drug: Drug: NA-831 - 0.10 mg/kg
NA-831 in nanoparticle inhalation formulation
Other Name: NA-831 is a neuroprotective and neurogenesis drug
Drug: Placebo- 0.10 mg/kg
Placebo in nanoparticle inhalation formulation
Other Name: Placebo Comparator
Drug: Drug: NA-831 - 0.20 mg/kg
NA-831 in nanoparticle inhalation formulation
Other Name: NA-81 is a neuroprotective drug
Drug: Placebo- 0.20 mg/kg
Placebo in nanoparticle inhalation formulation
Other Name: Placebo Comparator
Drug: Drug: GS-5734 - 1.00 mg/kg
GS-5734 in nanoparticle inhaled formulation
Other Name: GS-5734 (Remdesivir) is an antiviral drug
Drug: Placebo- 1.00 mg/kg
Placebo in nanoparticle inhalation formulation
Other Name: Placebo Comparator
Drug: Drug: GS-5734 - 2.00 mg/kg
GS-5734 in nanoparticle inhaled formulation
Other Name: GS-5734 (Remdesivir) is an anti-viral drug
Drug: Placebo- 2.00 mg/kg
Placebo in nanoparticle inhaled formulation
Other Name: Placebo Comparator
Combination Product: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation
Other Name: Combination therapy of NA-831 a neuroprotective drug and GS-5734 an antiviral drug
Combination Product: Placebo 0.10 mg + 1.00 mg/kg
The combined placebo are in nanoparticle inhaled formulation
Other Name: Placebo Comparator
Combination Product: Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)
The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation
Other Name: Combination therapy of NA-831, a neuroprotective drug and GS-5734, an antiviral drug
Combination Product: Placebo 0.20 mg + 2.00 mg/kg
Placebo 0.10 mg + 1.00 mg/kg
Other Name: Placebo Comparator
INCLUSION CRITERIA:
1. Healthy adult volunteers, aged 21 to 50 years old, men or women.
2. Subjects negative for human immunodeficiency virus (HIV antibody screen), Hepatitis B
virus surface Antigen (HBsAg) and Hepatitis C virus (HCV antibody screen).
3. Subjects who are willing to comply with the requirements of the study protocol, attend
scheduled visits and make themselves available for the duration of the study with
access to a consistent means of telephone contact.
4. Subjects who give written informed consent approved by the Internal Review Board
governing the site.
5. Satisfactory baseline medical assessment as assessed by physical examination and a
stable health status. Normal laboratory values must be within normal range of the
assessing site or show minor variations that are deemed not clinically significant as
judged by the Investigator and acceptable for study entry.
6. Accessible vein in the forearm for blood collection.
7. Female subjects of childbearing potential may be enrolled in the study if they have
negative urine pregnancy tests on the day of screening and day of admission.
8. Female subjects of non-childbearing potential due to surgical sterilization
(hysterectomy or bilateral oophorectomy or tubal ligation) or menopause.
9. Both male (if he has a partner of childbearing potential) and female subjects (of
childbearing potential) must agree to use adequate and reliable contraceptive measures
(e.g. spermicides, condoms, contraceptive pills, etc.) or practice abstinence
throughout the duration of the study (up to 30 days post-dosing).
EXCLUSION CRITERIA:
1. Subject previously diagnosed with COVID-19 or had been issued with a quarantine order
by the Center of Disease Control (CDC).
2. Presence of acute infection in the preceding 14 days, or presence of a temperature ≥
100.0 ˚F (oral or tympanic temperature assessment), or acute symptoms of any severity
on the scheduled date of admission.
3. History of severe drug and / or food allergies and / or known allergies to the trial
product or its components.
4. Female subject who is pregnant or breast-feeding.
5. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
, or immunosuppressive disorders.
6. Any neurological disease or history of significant neurological disorder (e.g.
meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré
syndrome [genetic/congenital or acquired]).
7. Evidence of clinically significant anemia (HB < 10 g/dL) or any other significant
active hematological disease, or having donated > 450 mL of blood within the past
three (3) months.
8. Participation or planned participation in a study involving the administration of an
investigational compound within the past four (4) months or during this study period.
9. Receipt of immunoglobulins and/or any blood products within nine (9) months of study
enrolment or planned administration of any of these products during the study period.
10. Evidence of Hepatitis B or C or HIV by laboratory testing.
11. A positive test result for drugs of abuse (except a positive test result associated
with prescription medication that has been reviewed and approved by the investigator)
or alcohol at screening.
12. Administration of any licensed vaccine within 30 days before the first study vaccine
dose.
13. Both male (if he has a partner of childbearing potential) and female subjects (of
childbearing potential) who are unwilling to use adequate contraception or practice
abstinence throughout the duration of the study (up to 84 days post-dosing).
14. Any condition that, in the opinion of the Investigator, would complicate or compromise
the study or well-being of the subject.
-
Coronavirus Research Institute
Sunnyvale, California, United States
Investigator: David Nguyen, MD
research@covri.org
Investigator: Markku Kurkinen, PhD
Brian Tran, MD
1-415-941-3133
BTran@neuroactiva.com
Markku Kurkinen, PhD
1-415-941-3133
MKurkinen@neuroactiva.com
Lloyd Tran, PhD, Study Director
NeuroActiva, Inc.