Study of the Safety of Therapeutic Treatment With an Immunomodulatory Agent (N-803) in Adults With COVID-19

Study Overview
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Brief Summary
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This is a phase 1b, randomized, blinded, placebo-controlled study in adult subjects with COVID-19. This clinical trial is designed to assess the safety and immunostimulatory activity of N-803.

Official Title
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Phase 1b, Randomized, Blinded, Placebo-controlled Study of the Safety of Therapeutic Treatment With an Immunomodulary Agent (N-803 in Adults With COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Biological: N-803
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age ≥ 18 years old. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. Has laboratory-confirmed positive novel coronavirus (SARS-CoV-2) test, as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen < 72 hours prior to enrollment, or meets the criteria to guide the evaluation and testing of patients under investigation (PUI) for COVID-19 (https://emergency.cdc.gov/han/2020/HAN00428.asp). Has a confirmed NEW score of 0-5. Has at least one of the following high-risk factors associated with a higher risk of COVID-19 progression: Age ≥ 60 years. Hypertension currently managed by at least 1 antihypertensive medication. Type 1 or 2 diabetes. Chronic obstructive pulmonary disease (COPD) diagnosed per medical history. Adequate respiratory and heart function, evidenced by the following laboratory results: Respiratory rate (RR) < 20 breaths per minute (bpm). Heart rate (HR) < 90 beats per minute (bpm). Arterial oxygen saturation (SaO2) > 93% on room air. Agrees to the collection of nasopharyngeal (NP) swabs and venous blood per protocol. Ability to participate in required study visits and participate in adequate follow-up, as required by this protocol. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception while on study and for at least 1 month after the last dose of N-803. Non-sterile male subjects must agree to use a condom while on study and for up to 1 month after the last dose of N-803. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), oral contraceptives, and abstinence. Exclusion Criteria: Shortness of breath or hypoxia defined by a ratio of partial pressure of arterial oxygen to the percentage of inspired oxygen (PaO2/FiO2) ≤ 300 mmHg or signs of serious lower airway disease. Signs or symptoms of acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS)/shock, or cardiac failure; or need for supplemental oxygen. Inflammatory markers (C-reactive protein [CRP], lactate dehydrogenase [LDH], d-dimer, ferritin, and IL-6) > 1.5 × upper limit of normal (ULN). Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol. Pregnant and nursing women. A negative serum or urine pregnancy test during screening prior to the first dose must be documented before N-803 is administered to a female subject of child-bearing potential.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>N-803 Recombinant human super agonist interleukin-15 (IL-15) complex | Biological: N-803<br>* Recombinant human super agonist interleukin-15 (IL-15) complex<br>|
| Placebo Comparator: Placebo Arm<br>Sterile saline solution | Other: Saline<br>* Sterile saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary safety and efficacy evaluation of N-803 by adverse event (AE) incidence | AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0 | 2 weeks | 
| Preliminary safety and efficacy evaluation of N-803 by subject clinical status using a the 7-point ordinal scale. | The 7-point ordinal scale is an assessment of the clinical status and is performed as the first assessment on each study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. | 2 weeks | 
| Preliminary safety and efficacy evaluation of N-803 | Preliminary safety and efficacy evaluation of N-803 by changes in lymphocyte counts. Incidence of lymphopenia (ie, absolute lymphocyte count [ALC] < 1000/mm3) during COVID-19 infection. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Further evaluate efficacy of N-803 using changes to the National Early Warning Score (NEWS) | National Early Warning Score (NEWS) is based on 7 clinical parameters: respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, and level of consciousness. | 2 weeks | 
| Further evaluate the safety of N-803 in hemoglobin | Further evaluate the safety of N-803 using change from baseline in hemoglobin | 2 weeks | 
| Further evaluate the safety of N-803 using platelets | Further evaluate the safety of N-803 using change from baseline in platelets | 2 weeks | 
| Further evaluate the safety of N-803 using white blood cell count | Further evaluate the safety of N-803 using change from baseline in white blood cell count | 2 weeks |