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

NCT ID: NCT04480333

Last Updated: 2020-07-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-15

Study Completion Date

2021-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Drug: NA-831 - 0.10 mg/kg

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

Group Type EXPERIMENTAL

Drug: NA-831 - 0.10 mg/kg

Intervention Type DRUG

NA-831 in nanoparticle inhalation formulation

Comparable Placebo- 0.10 mg/kg

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

Group Type PLACEBO_COMPARATOR

Placebo- 0.10 mg/kg

Intervention Type DRUG

Placebo in nanoparticle inhalation formulation

Drug: NA-831 - 0.20 mg/kg

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

Group Type EXPERIMENTAL

Drug: NA-831 - 0.20 mg/kg

Intervention Type DRUG

NA-831 in nanoparticle inhalation formulation

Comparable Placebo- 0.20 mg/kg

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

Group Type PLACEBO_COMPARATOR

Placebo- 0.20 mg/kg

Intervention Type DRUG

Placebo in nanoparticle inhalation formulation

Drug: GS-5734 - 1.00 mg/kg

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

Group Type EXPERIMENTAL

Drug: GS-5734 - 1.00 mg/kg

Intervention Type DRUG

GS-5734 in nanoparticle inhaled formulation

Comparable Placebo- 1.00 mg.kg

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

Group Type PLACEBO_COMPARATOR

Placebo- 1.00 mg/kg

Intervention Type DRUG

Placebo in nanoparticle inhalation formulation

Drug: GS-5734 - 2.00 mg/kg

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

Group Type EXPERIMENTAL

Drug: GS-5734 - 2.00 mg/kg

Intervention Type DRUG

GS-5734 in nanoparticle inhaled formulation

Comparable Placebo - 2.00 mg/kg

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

Group Type PLACEBO_COMPARATOR

Placebo- 2.00 mg/kg

Intervention Type DRUG

Placebo in nanoparticle inhaled formulation

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

Group Type EXPERIMENTAL

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

Intervention Type COMBINATION_PRODUCT

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

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

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

Group Type PLACEBO_COMPARATOR

Placebo 0.10 mg + 1.00 mg/kg

Intervention Type COMBINATION_PRODUCT

The combined placebo are in nanoparticle inhaled formulation

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

Group Type EXPERIMENTAL

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

Intervention Type COMBINATION_PRODUCT

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

Placebo- 0.20 mg/kg + 2.00mg/kg

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

Group Type PLACEBO_COMPARATOR

Placebo 0.20 mg + 2.00 mg/kg

Intervention Type COMBINATION_PRODUCT

Placebo 0.10 mg + 1.00 mg/kg

Interventions

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Drug: NA-831 - 0.10 mg/kg

NA-831 in nanoparticle inhalation formulation

Intervention Type DRUG

Placebo- 0.10 mg/kg

Placebo in nanoparticle inhalation formulation

Intervention Type DRUG

Drug: NA-831 - 0.20 mg/kg

NA-831 in nanoparticle inhalation formulation

Intervention Type DRUG

Placebo- 0.20 mg/kg

Placebo in nanoparticle inhalation formulation

Intervention Type DRUG

Drug: GS-5734 - 1.00 mg/kg

GS-5734 in nanoparticle inhaled formulation

Intervention Type DRUG

Placebo- 1.00 mg/kg

Placebo in nanoparticle inhalation formulation

Intervention Type DRUG

Drug: GS-5734 - 2.00 mg/kg

GS-5734 in nanoparticle inhaled formulation

Intervention Type DRUG

Placebo- 2.00 mg/kg

Placebo in nanoparticle inhaled formulation

Intervention Type DRUG

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

Intervention Type COMBINATION_PRODUCT

Placebo 0.10 mg + 1.00 mg/kg

The combined placebo are in nanoparticle inhaled formulation

Intervention Type 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

Intervention Type COMBINATION_PRODUCT

Placebo 0.20 mg + 2.00 mg/kg

Placebo 0.10 mg + 1.00 mg/kg

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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NA-831 is a neuroprotective and neurogenesis drug Placebo Comparator NA-81 is a neuroprotective drug Placebo Comparator GS-5734 (Remdesivir) is an antiviral drug Placebo Comparator GS-5734 (Remdesivir) is an anti-viral drug Placebo Comparator Combination therapy of NA-831 a neuroprotective drug and GS-5734 an antiviral drug Placebo Comparator Combination therapy of NA-831, a neuroprotective drug and GS-5734, an antiviral drug Placebo Comparator

Eligibility Criteria

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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.

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Minimum Eligible Age

21 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biomed Industries, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lloyd Tran, PhD

Role: STUDY_DIRECTOR

Biomed Industries, Inc.

Locations

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Coronavirus Research Institute

Sunnyvale, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Brian Tran, MD

Role: CONTACT

1-415-941-3133

Markku Kurkinen, PhD

Role: CONTACT

1-415-941-3133

Facility Contacts

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David Nguyen, MD

Role: primary

Lloyd Tran, PhD

Role: backup

Other Identifiers

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NEUROSIVIR

Identifier Type: -

Identifier Source: org_study_id

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