DAS181 for STOP COVID-19

Study Overview
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Brief Summary
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It is a multicenter, randomized, placebo-controlled, double-blind study. The study population is defined as subjects diagnosed with lower respiratory tract COVID-19 who require supplemental oxygen ≥2 LPM at the time of randomization.

Detailed Description
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The first stage is randomized, double-blind study to confirm the optimal dose of the study. Twenty-two (n=22) subjects with COVID-19 and clinically significant impairment of respiratory function will be enrolled to evaluate the two dosing regimens (4.5mg-q.d or 4.5mg-b.i.d) of DAS181. At the end of Stage 1, the Sponsor will evaluate the dose regimen based on the safety and efficacy assessments of the data. An optimal dose will be selected to proceed to Stage 2. The second stage is a randomized, placebo-controlled and double-blind study to expand enrollment with an additional eighty-two (n=82) subjects to provide adequate power to potentially demonstrate statistically significant therapeutic efficacy.

Official Title
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DAS181 for COVID-19: A Phase II Multicenter, Randomized, Placebo-Controlled, Double-Blind Study

Conditions
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COVID-19

Intervention / Treatment
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* Drug: DAS181
* Drug: Placebo
* Drug: DAS181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be ≥18 years of age Provide adequate medical history to permit accurate stratification by health status Prior to SARS CoV 2 infection, has no chronic or recurring requirement for supplemental oxygen Have lower respiratory tract infection (LRTI) confirmed by imaging Has laboratory-confirmation of the presence of SARS-CoV-2 in the respiratory tract At the time of randomization, requires supplemental oxygen ≥2 LPM for treatment of hypoxia or pulmonary stress as evidenced by at least one of the following: Respiratory rate ≥ 30 breaths/min SpO2 ≤93% at rest PaO2/FiO2≤300 mmHg Showing the progression of lung lesions within 24 to 48h by >50% If female, subject must meet one of the following conditions: Not be of childbearing potential or Be of childbearing potential and have a negative urine/serum pregnancy test and agrees to practice an acceptable method of contraception Non-vasectomized males are required to practice effective birth control methods Capable of understanding and complying with procedures as outlined in the protocol Provides signed informed consent prior to the initiation of any screening or study-specific procedures Exclusion Criteria: At the time of randomization, classified as critical (life-threatening) disease Subjects currently receiving any other investigational drug, as part of a clinical trial or under emergency approval for SARS-CoV-2 Subjects who are known asthmatic patients or HIV-positive Subjects who are currently receiving inhaled biologics or anti-viral agents Subjects with severe sepsis due to either their SARS-CoV-2 infection or a concurrent viral, bacterial, or fungal infection with vital organ failure or required vasopressors to maintain blood pressure Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2xULN Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance. Subjects with known hypersensitivity to DAS181 and/or any of its components.

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: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAS181 b.i.d.+ standard local care for COVID-19<br>4.5 mg DAS181 b.i.d nebulized inhalation for 10 consecutive days + standard local care for COVID-19 | Drug: DAS181<br>* 4.5 mg q.d.<br>|
| Placebo Comparator: Placebo+ standard local care for COVID-19<br>nebulized inhalation for 10 consecutive days + standard local care for COVID-19 | Drug: Placebo<br>* q.d. or b.i.d.<br>|
| Experimental: DAS181 q.d.+ standard local care for COVID-19<br>4.5 mg placebo q.d. nebulized inhalation for 10 consecutive days + standard local care for COVID-19 | Drug: DAS181<br>* 4.5 mg b.i.d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of subjects return to room air (RTRA) |  | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of subjects who have recovered | Percent of subjects who reach level 1 of COVID-19 Clinical Classification (discharged or return to normal activity) | Day 5, 10, 14, 21, 28 | 
| Improved COVID-19 Clinical Classification | time to Improved COVID-19 Clinical Classification 1 to 6 (where higher score means worse outcome) | Day 28 | 
| Return To Room Air (RTRA) | Percent of subjects RTRA | Day 10, 21, 28 | 
| Percent of subjects who achieve clinical stability |  | Day 28 | 
| SARS-CoV-2 RNA undetectable | Time to | Day 28 | 
| Clinical Deterioration | Time to | Day 28 | 
| Percent of subjects discharged | Percent of subjects discharge | Day 14, 21, 28 | 
| Death (all cause) | Time to | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Lower Respiratory Tract Disease, DAS181, SARS-CoV-2, Coronavirus, Hypoxemia, Ansun