Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and NA-831

NCT04480333 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: NEUROSIVIR
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Covid19; Corona Virus Infection; Severe Acute Respiratory Syndrome; Severe Acute Respiratory Infection; Severe Acute Respiratory Syndrome (SARS) Pneumonia; Severe Acute Respiratory Syndrome of Upper Respiratory Tract; Neurodegeneration; Neuroinflammatory Response

Keywords

Covid-19; Corona Virus Infection; Severe Acute Respiratory Syndrome; Severe Acute Respiratory Infection; Severe Acute Respiratory Syndrome (SARS) Pneumonia; Severe Acute Respiratory Syndrome of Upper Respiratory Tract; Neurodegeneration; Neuroinflammation; Cognitive decline

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants Experiencing any Treatment-Emergent Adverse Events

  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

  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 Outcomes (7)

• Maximum Concentration (Cmax) - Pharmacokinetic Assessment

  7 days

• Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment

  7 days

• AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment

  7 days

• Area Under the Curve Extrapolated to Infinity (AUC0-∞)

  7 days

• Half-Life (t1/2) - Pharmacokinetic Assessment

  7 days

Study Arms (12)

Drug: NA-831 - 0.10 mg/kg

EXPERIMENTAL

3 Subjects will take inhaled formulation of NA-831 once a day for 5 days

Drug: Drug: NA-831 - 0.10 mg/kg

Comparable Placebo- 0.10 mg/kg

PLACEBO COMPARATOR

3 subjects will take inhaled formulation of placebo once a day for 5 days

Drug: Placebo- 0.10 mg/kg

Drug: NA-831 - 0.20 mg/kg

EXPERIMENTAL

6 Subjects will take inhaled formulation of NA-831 once a day for 5 days

Drug: Drug: NA-831 - 0.20 mg/kg

Comparable Placebo- 0.20 mg/kg

PLACEBO COMPARATOR

3 subjects will take inhaled formulation of placebo once a day for 5 days

Drug: Placebo- 0.20 mg/kg

Drug: GS-5734 - 1.00 mg/kg

EXPERIMENTAL

3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days

Drug: Drug: GS-5734 - 1.00 mg/kg

Comparable Placebo- 1.00 mg.kg

PLACEBO COMPARATOR

3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days

Drug: Placebo- 1.00 mg/kg

Drug: GS-5734 - 2.00 mg/kg

EXPERIMENTAL

6 Subjects will take inhaled formulation of GS-5734 once a day for 5 days

Drug: Drug: GS-5734 - 2.00 mg/kg

Comparable Placebo - 2.00 mg/kg

PLACEBO COMPARATOR

3 Subjects will take inhaled formulation of GS-5734 once a day for 5 days

Drug: Placebo- 2.00 mg/kg

Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)

EXPERIMENTAL

3 Subjects- will take inhaled formulation NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) once/day for 5 days

Combination Product: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)

Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg

PLACEBO COMPARATOR

3 Subjects - inhaled formulation of placebo once/day for 5 days

Combination Product: Placebo 0.10 mg + 1.00 mg/kg

Drugs: NA-831( 0.20 mg/kg) + GS-5734 (2.00 mg/kg)

EXPERIMENTAL

6 Subjects- inhaled formulation of NA-831 (0.20 mg/kg) + GS-5734 (2.00 mg/kg) once/day for 5 days

Combination Product: Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)

Placebo- 0.20 mg/kg + 2.00mg/kg

PLACEBO COMPARATOR

3 Subjects- inhaled formulation of placebo once/day for 5 days

Combination Product: Placebo 0.20 mg + 2.00 mg/kg

Interventions

Drug: NA-831 - 0.10 mg/kg DRUG

NA-831 in nanoparticle inhalation formulation

Also known as: NA-831 is a neuroprotective and neurogenesis drug

Drug: NA-831 - 0.10 mg/kg

Placebo- 0.10 mg/kg DRUG

Placebo in nanoparticle inhalation formulation

Also known as: Placebo Comparator

Comparable Placebo- 0.10 mg/kg

Drug: NA-831 - 0.20 mg/kg DRUG

NA-831 in nanoparticle inhalation formulation

Also known as: NA-81 is a neuroprotective drug

Drug: NA-831 - 0.20 mg/kg

Placebo- 0.20 mg/kg DRUG

Placebo in nanoparticle inhalation formulation

Also known as: Placebo Comparator

Comparable Placebo- 0.20 mg/kg

Drug: GS-5734 - 1.00 mg/kg DRUG

GS-5734 in nanoparticle inhaled formulation

Also known as: GS-5734 (Remdesivir) is an antiviral drug

Drug: GS-5734 - 1.00 mg/kg

Placebo- 1.00 mg/kg DRUG

Placebo in nanoparticle inhalation formulation

Also known as: Placebo Comparator

Comparable Placebo- 1.00 mg.kg

Drug: GS-5734 - 2.00 mg/kg DRUG

GS-5734 in nanoparticle inhaled formulation

Also known as: GS-5734 (Remdesivir) is an anti-viral drug

Drug: GS-5734 - 2.00 mg/kg

Placebo- 2.00 mg/kg DRUG

Placebo in nanoparticle inhaled formulation

Also known as: Placebo Comparator

Comparable Placebo - 2.00 mg/kg

Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) COMBINATION_PRODUCT

The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation

Also known as: Combination therapy of NA-831 a neuroprotective drug and GS-5734 an antiviral drug

Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)

Placebo 0.10 mg + 1.00 mg/kg COMBINATION_PRODUCT

The combined placebo are in nanoparticle inhaled formulation

Also known as: Placebo Comparator

Placebo- 0.10- mg/kg placebo+1.00 mg mg/kg

Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg) COMBINATION_PRODUCT

The combined NA-831 and GS-5734 are in nanoparticle inhaled formulation

Also known as: Combination therapy of NA-831, a neuroprotective drug and GS-5734, an antiviral drug

Drugs: NA-831( 0.20 mg/kg) + GS-5734 (2.00 mg/kg)

Placebo 0.20 mg + 2.00 mg/kg COMBINATION_PRODUCT

Placebo 0.10 mg + 1.00 mg/kg

Also known as: Placebo Comparator

Placebo- 0.20 mg/kg + 2.00mg/kg

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biomed Industries, Inc.: lead

Study Sites (1)

Coronavirus Research Institute

Sunnyvale, California, 94086, United States

RECRUITING

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Severe Acute Respiratory Syndrome; Pneumonia; Nerve Degeneration; Neuroinflammatory Diseases; Cognitive Dysfunction

Interventions

remdesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Diseases; Inflammation; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Lloyd Tran, PhD

  Biomed Industries, Inc.

  STUDY DIRECTOR

Central Study Contacts

Brian Tran, MD

CONTACT

1-415-941-3133; BTran@neuroactiva.com

Markku Kurkinen, PhD

CONTACT

1-415-941-3133; MKurkinen@neuroactiva.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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: 1. mg/kg GS-5734, number of subjects N=2 and 2 subjects on placebos 2. 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.

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 21, 2020
• Study Start: September 15, 2020
• Primary Completion: December 31, 2020
• Study Completion: March 31, 2021
• Last Updated: July 21, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 90 days after the completion of the study
• Access Criteria: to be determined

Locations

US (1)