Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19

Study Overview
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Brief Summary
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AD17002 enhances nasal mucosal innate immunity and has met safety and efficacy endpoints in nasal adjuvant or intranasal immunomodulator studies. The aim of this study is assessing the safety and efficacy of AD17002 in treating patients with mild to moderate COVID-19. All participants will be 1:1:1 divided, randomly, and receive standard of treatment. In addition, participants will be given either placebo, 20 or 40 μg of AD17002 via intranasal route and clinical progresses will be compared.

Official Title
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A Phase 2/3, Double-blind, Randomized, Placebo-controlled, 3-arm Study to Evaluate the Safety, and Efficacy of AD17002 (LTh[αK]) Intranasal Spray in Male and Female Participants Aged 18 to 65 Years With Mild to Moderate COVID 19

Conditions
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COVID-19

Intervention / Treatment
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* Biological: AD17002 + Formulation buffer
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 and ≤65 years old. Laboratory confirmed SARS-CoV-2 infection, with first positive PCR test results within the past 48 hours of randomization. Participants with COVID-19 symptoms within 5 days prior to the day of randomization, based on the following criteria: At least TWO of the following symptoms: Stuffy/runny nose, sore throat, shortness of breath, cough, low energy/tiredness, muscle/body aches, headache, chill/shivering, Fever (≥ 38ºC), nausea, vomiting, diarrhea, and loss of taste or smell. Have a mild or moderate form of COVID-19 defined as: respiratory rate ≤30 breaths per minute, heart rate ≤125 beats per minute; with saturation of oxygen (SpO2) ≥93% on room air at sea level No clinical signs listed in Inclusion Criteria #3 indicative of Severe Severity Have a negative pregnancy test at Screening (for female participants of childbearing potential). Participant or the participant's legal representative understands the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent. Provide written informed consent for the study and willing to adhere to dose regimen and visit schedules. Exclusion Criteria: Participant has clinical signs suggestive of severe illnesses with SPO2≤94. Sign of severe pneumonia as determined by treating physician on X-ray or SPO2 Participant has CT≥25 at screening Participation in any other clinical study of an investigational agent treatment for SARS-CoV-2 infection within 30 days prior to the first IMP dosing. Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 prior to PCR screening. Participant with breakthrough SARS-CoV-2 infection within 2 weeks of SARS-CoV-2 vaccination. History of severe renal disease (treatment with dialysis or phosphate binders) or clinically apparent hepatic impairment (e.g., jaundice, cholestasis, hepatic synthetic impairment, active hepatitis). Impaired cardiac function or clinically significant cardiac diseases as judged by the Investigator. History of anaphylaxis reaction to any known or unknown cause. Immunosuppressed persons as result of illness (e.g., HIV infection) or treatment. Documented history of Bell's palsy. History of allergic reaction to kanamycin. Immunosuppressive treatment within 3 months prior to the Screening Visit. Intranasal medication or nasal topical treatment at the time of screen and study. Assessed by the Investigator to be ineligible to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Eligible participants who are confirmed for SARS-CoV-2 infection by PCR with CT values ≤28 will be randomized (1:1:1) and received AD17002 0 (placebo), 20 or 40 μg via intranasal route on Day 1, 3 and 5.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Comparator<br>Participants will receive placebo (formulation buffer) on treatment days 1, 3 and 5. | Biological: Placebo<br>* Formulation buffer<br>* Other names: Formulation buffer control;|
| Experimental: Low dose treatment group<br>Participants will receive 20 μg of AD17002 in formulation buffer on treatment days 1, 3 and 5. | Biological: AD17002 + Formulation buffer<br>* Intranasal innate immune modulator<br>* Other names: LTh(αK);|
| Experimental: High dose treatment group<br>Participants will receive 40 μg of AD17002 in formulation buffer on treatment days 1, 3 and 5. | Biological: AD17002 + Formulation buffer<br>* Intranasal innate immune modulator<br>* Other names: LTh(αK);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease improvement | Defined as time to achieving ≥1 decrease on WHO 11-point Clinical Progression Scale | [Day 1 to Day 29] | 
| Time to achieving the Patient Acceptable Symptom State (PASS) | Defined as the value of symptoms the patient considered to be well-being thresholds of the symptoms and function. The study incorporates the most widely used anchoring question to identify PASS cut-off points, which is: Taking into account all your daily activities, do you consider your current state satisfactory in relation to pain level and functional impairment? The response options were Yes or No. | [Day 1 to Day 29] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital signs evaluation | Measuring the changes to cardiac functions | [Day 1 to Day 29] | 
| Physical examination | Measuring changes to physical appearances. | [Day 1 to Day 29] | 
| Clinical laboratory assessment | Assessing the changes to hematological parameters | [Day 1 to Day 29] | 
| Adverse events assessment | Adverse events graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 1 (Mild) : asymptomatic or mild symptoms Grade 2 (Moderate): Local, Minimal, Moderate or noninvasive Grade 3 (Severe): Severe or medically significant but not immediately life-threatening Grade 4 (Life-threatening): Life-threatening consequences; urgent intervention indicated Grade 5 (Fatal): Death related to AE | [Day 1 to Day 29] | 
| Treatment-emergent adverse events assessment (TEAE) | Measuring the proportion of participants with TEAE leading to investigational medicinal products (IMPs) discontinuation. AE will be presented by the following categories: Any TEAE Treatment-related TEAE Grade 3-4, drug-related TEAE Drug-related TEAE leading to death | [Day 1 to Day 29] | 
| Nasal tolerability examination | Assessing the nasal symptoms by PI or delegated personnel or qualified ear, nose, and throat (ENT) specialist Symptoms include color of mucosa, turbinate swelling (middle concha and inferior concha), secretion, infection, post-nasal drip, crusting, sign of bleeding, and polyps. | [Day 1 to Day 29] | 
| Viral clearance | Time to clearance of SARS-CoV-2, defined as 2 consecutive negative oropharyngeal swabs by RT-PCR test and report as cycle threshold (CT) | [Day 1 to Day 29] | 
| Viral clearance rate by PCR | Changes of CT of RdRp (a.k.a. nsp12) N and E gene assayed by RT-PCR test | [Day 1 to Day 29] | 
| PASS evaluation | Proportion of subjects achieving PASS at each visit | [Day 1 to Day 29] | 
| Clinical Progression Scale analysis | Proportion of subjects achieving ≧1 decrease on WHO 11-point Clinical Progression Scale at each visit | [Day 1 to Day 29] | 
| Days of COVID-19 symptomatic hospitalization | Days participants in hospital due to infection. | [Day 1 to Day 29] | 
| Proportion of COVID-19 symptomatic hospitalization | Proportion of participants has been hospitalized due to infection. | [Day 1 to Day 29] | 
| Oxygen supplement treatment | Days of participants receive oxygen supplement. | [Day 1 to Day 29] | 
| Oxygen supplement treatment rate | Oxygen supplement receiving rates among infected participants | [Day 1 to Day 29] | 
| Symptom relieve days | Time to alleviation of each predefined COVID-19-related symptoms | [Day 1 to Day 29] | 
| Symptom severity report | Severity of each targeted COVID-19 symptoms An assessment of common COVID-19-related symptoms according to the FDA Guidance for Industry: Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment Symptom Score Guide: 0= None; 1= Mild; 2= Moderately; 3= Severe | [Day 1 to Day 29] | 
| Mortality rate report | Proportion of participants with death (all cause) | [Day 1 to Day 29] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunomodulator, intranasal, epithelial, nasal mucosal