- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04480333
Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and NA-831 (NEUROSIVIR)
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
Study Overview
Status
Conditions
Intervention / Treatment
- Drug: Drug: NA-831 - 0.10 mg/kg
- Drug: Placebo- 0.10 mg/kg
- Drug: Drug: NA-831 - 0.20 mg/kg
- Drug: Placebo- 0.20 mg/kg
- Drug: Drug: GS-5734 - 1.00 mg/kg
- Drug: Placebo- 1.00 mg/kg
- Drug: Drug: GS-5734 - 2.00 mg/kg
- Drug: Placebo- 2.00 mg/kg
- Combination product: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
- Combination product: Placebo 0.10 mg + 1.00 mg/kg
- Combination product: Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)
- Combination product: Placebo 0.20 mg + 2.00 mg/kg
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Sunnyvale, California, United States, 94086
- Recruiting
- Coronavirus Research Institute
-
Contact:
- David Nguyen, MD
- Email: research@covri.org
-
Contact:
- Lloyd Tran, PhD
- Email: LTran@neuroactiva.com
-
Sub-Investigator:
- Markku Kurkinen, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA:
- Healthy adult volunteers, aged 21 to 50 years old, men or women.
- Subjects negative for human immunodeficiency virus (HIV antibody screen), Hepatitis B virus surface Antigen (HBsAg) and Hepatitis C virus (HCV antibody screen).
- 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.
- Subjects who give written informed consent approved by the Internal Review Board governing the site.
- 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.
- Accessible vein in the forearm for blood collection.
- 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.
- Female subjects of non-childbearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause.
- 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:
- Subject previously diagnosed with COVID-19 or had been issued with a quarantine order by the Center of Disease Control (CDC).
- 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.
- History of severe drug and / or food allergies and / or known allergies to the trial product or its components.
- Female subject who is pregnant or breast-feeding.
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, , or immunosuppressive disorders.
- Any neurological disease or history of significant neurological disorder (e.g. meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré syndrome [genetic/congenital or acquired]).
- 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.
- 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.
- 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.
- Evidence of Hepatitis B or C or HIV by laboratory testing.
- 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.
- Administration of any licensed vaccine within 30 days before the first study vaccine dose.
- 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).
Any condition that, in the opinion of the Investigator, would complicate or compromise the study or well-being of the subject.
-
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Drug: NA-831 - 0.10 mg/kg
3 Subjects will take inhaled formulation of NA-831 once a day for 5 days
|
NA-831 in nanoparticle inhalation formulation
Other Names:
|
Placebo Comparator: Comparable Placebo- 0.10 mg/kg
3 subjects will take inhaled formulation of placebo once a day for 5 days
|
Placebo in nanoparticle inhalation formulation
Other Names:
|
Experimental: Drug: NA-831 - 0.20 mg/kg
6 Subjects will take inhaled formulation of NA-831 once a day for 5 days
|
NA-831 in nanoparticle inhalation formulation
Other Names:
|
Placebo Comparator: Comparable Placebo- 0.20 mg/kg
3 subjects will take inhaled formulation of placebo once a day for 5 days
|
Placebo in nanoparticle inhalation formulation
Other Names:
|
Experimental: Drug: GS-5734 - 1.00 mg/kg
3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
|
GS-5734 in nanoparticle inhaled formulation
Other Names:
|
Placebo Comparator: Comparable Placebo- 1.00 mg.kg
3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
|
Placebo in nanoparticle inhalation formulation
Other Names:
|
Experimental: Drug: GS-5734 - 2.00 mg/kg
6 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
|
GS-5734 in nanoparticle inhaled formulation
Other Names:
|
Placebo Comparator: Comparable Placebo - 2.00 mg/kg
3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days
|
Placebo in nanoparticle inhaled formulation
Other Names:
|
Experimental: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
3 Subjects- will take inhaled formulation NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) once/day for 5 days
|
The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation
Other Names:
|
Placebo Comparator: Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg
3 Subjects - inhaled formulation of placebo once/day for 5 days
|
The combined placebo are in nanoparticle inhaled formulation
Other Names:
|
Experimental: Drugs: NA-831( 0.20 mg/kg) + GS-5734 (2.00 mg/kg)
6 Subjects- inhaled formulation of NA-831 (0.20 mg/kg) + GS-5734 (2.00 mg/kg) once/day for 5 days
|
The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation
Other Names:
|
Placebo Comparator: Placebo- 0.20 mg/kg + 2.00mg/kg
3 Subjects- inhaled formulation of placebo once/day for 5 days
|
Placebo 0.10 mg + 1.00 mg/kg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Participants Experiencing any Treatment-Emergent Adverse Events
Time Frame: First dose date up to Day 30 Follow-up Assessment
|
AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0
|
First dose date up to Day 30 Follow-up Assessment
|
Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities
Time Frame: First dose date up to Day 30 Follow-up Assessment
|
This will be assessed at various time points by clinical laboratory tests and vital signs.
|
First dose date up to Day 30 Follow-up Assessment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Concentration (Cmax) - Pharmacokinetic Assessment
Time Frame: 7 days
|
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.
|
7 days
|
Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment
Time Frame: 7 days
|
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
|
7 days
|
AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment
Time Frame: 7 days
|
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
|
7 days
|
Area Under the Curve Extrapolated to Infinity (AUC0-∞)
Time Frame: 7 days
|
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
|
7 days
|
Half-Life (t1/2) - Pharmacokinetic Assessment
Time Frame: 7 days
|
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.
|
7 days
|
Volume of Distribution (Vd) - Pharmacokinetic Assessment
Time Frame: 7 days
|
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.
|
7 days
|
Clearance [CL] - Pharmacokinetic Assessment
Time Frame: 7 days
|
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.
|
7 days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Lloyd Tran, PhD, NeuroActiva, Inc.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Lung Diseases
- Disease Attributes
- Disease
- Severe Acute Respiratory Syndrome
- COVID-19
- Coronavirus Infections
- Syndrome
- Infections
- Communicable Diseases
- Virus Diseases
- Pneumonia
- Respiratory Tract Infections
- Nerve Degeneration
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antimetabolites
- Protective Agents
- Antiviral Agents
- Remdesivir
- Neuroprotective Agents
Other Study ID Numbers
- NEUROSIVIR
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Severe Acute Respiratory Syndrome
-
Assistance Publique - Hôpitaux de ParisCompletedSevere Acute Respiratory Syndrome Coronavirus 2 | Severe Acute Respiratory Distress SyndromeFrance
-
Oneness Biotech Co., Ltd.CompletedDisease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)United States
-
Hôpital Universitaire SahloulCompleted
-
Wits Health Consortium (Pty) LtdFred Hutchinson Cancer Center; Janssen Vaccines & Prevention B.V.; National Institute... and other collaboratorsCompletedSARS (Severe Acute Respiratory Syndrome)South Africa
-
TakedaCompletedPrevention of Infection Disease Caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)Japan
-
Laboratorios Silanes S.A. de C.V.CompletedSevere Acute Respiratory Syndrome Coronavirus 2Mexico
-
Throne Biotechnologies Inc.Not yet recruitingSevere Acute Respiratory Syndrome (SARS) Pneumonia
-
Massachusetts General HospitalXijing Hospital; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Niguarda...CompletedCoronavirus | SARS (Severe Acute Respiratory Syndrome)United States, Sweden
-
University of SaskatchewanGovernment of Canada; Vaccine Formulation Institute (VFI); Government of Saskatchewan and other collaboratorsCompletedSevere Acute Respiratory Syndrome Coronavirus 2Canada
-
Pulmoquine Therapeutics, IncRockefeller UniversityCompletedSevere Acute Respiratory Syndrome Coronavirus 2United States
Clinical Trials on Drug: NA-831 - 0.10 mg/kg
-
NeuroActiva, Inc.CompletedNeurocognitive Disorders | Neurodegenerative Diseases | Cognitive Impairment | Alzheimer Disease | Tauopathies | Mild Cognitive Impairment | Dementia, Vascular | Dementia With Lewy Bodies | Alzheimer Dementia | Cognitive DisorderNew Zealand
-
NoNO Inc.University of CalgaryCompletedStroke, AcuteUnited States, Ireland, Korea, Republic of, Canada, Sweden, Germany, United Kingdom, Australia
-
AbbVie (prior sponsor, Abbott)Genentech, Inc.CompletedNon-Small Cell Lung Cancer (NSCLC)United States, Canada, France, Singapore, Taiwan
-
NeuroActiva, Inc.Biomed Industries, Inc.UnknownCovid19 | SARS-CoV-2 | SARS-CoV Infection | SARS (Severe Acute Respiratory Syndrome)New Zealand, United States
-
ShireCompletedShort Bowel SyndromeUnited States, Denmark, France, Canada, Belgium, Netherlands, Poland, United Kingdom
-
Viridian Therapeutics, Inc.Recruiting
-
NeuroActiva, Inc.Biomed Industries, Inc.RecruitingCoronavirus Infection | Severe Acute Respiratory Syndrome Coronavirus 2 | Severe Acute Respiratory InfectionUnited States
-
Omeros CorporationRecruitingParoxysmal Nocturnal HemoglobinuriaGermany, Greece, Switzerland, United Kingdom
-
Cubist Pharmaceuticals LLCCompletedProven or Suspected Gram-negative Bacterial Infection | Peri-operative Prophylaxis
-
London School of Hygiene and Tropical MedicineUniversity Medical Center Nijmegen; Centre national de recherche et de formation...Completed