DAS181 for Patients With Severe Hospitalized Flu and SAD-RVs (COVID-19)

Study Overview
=================
Brief Summary
-----------------
This is a Phase IIb study consisting of two cohorts to evaluate efficacy, safety and pharmacokinetics of DAS181 in IFV infection. An approximate total of 280 subjects will be enrolled into this study.

Detailed Description
-----------------
Cohort 1: It is designed as a two stage, multi-center, randomized, double-blind, two parallel doses, placebo-controlled study that will investigate the efficacy of DAS181 for the treatment of serious IFV in hospitalized patients who suffered from acute hypoxemia requiring supplemental oxygen therapy. Cohort 2: It is designed as an open-label study that will investigate the efficacy of DAS181 for the treatment of patients with sever IFV but not eligible for Cohort 1 and non-IFV SAD viral infection, e.g. parainfluenza virus, human metapneumovirus, enterovirus and all strains of β-coronaviruses (including but not limited to SARS-CoV-2), with hypoxemia requiring supplemental oxygen therapy.

Official Title
-----------------
A Phase IIb Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Severe Influenza Infection

Conditions
-----------------
Influenza Infection, SAD-RV Infection and COVID-19

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria of Cohort 1 #4 is adapted from the Flu guideline in China (2018) and community acquired pneumonia (CAP) guideline in China (2016) Cohort 1: Subjects must meet all of the following inclusion criteria at the time of randomization to be eligible for participation in this study: Males and Females ≥18 years old Diagnosed as influenza (IFV) infection within 3 days before randomization Requires, at the time of randomization, supplemental oxygen ≥2 LPM due to hypoxemia Subjects are severely ill In the opinion of investigator, subjects will be hospitalized at least 1 week. If female, subject must not be pregnant or nursing Cohort 2: Subjects must meet all of the following inclusion criteria at the time of randomization to be eligible for participation in this study: Males and Females ≥18 years old Hypoxemia Subjects fulfill one of the following conditions: IFV subjects who are eligible for all inclusion criteria of Cohort 1 except for acute hypoxemia at enrollment. Subjects confirmed with non-IFV SAD viral infection. Same in inclusion criteria #5 to #8 in Cohort 1. Exclusion Criteria Cohort 1 and 2: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study: Subjects requiring mechanical, Bi-PAP or CPAP ventilation at randomization. Life expectancy less than 30 days. Subjects with conscious disturbance (slow response, drowsy, restlessness, anxiety, confusion, twitching or convulsion) Subjects with unstable hemodynamics such as systolic blood pressure < 90 mmHg or septic shock Subjects with BUN≧7.14 mmol/L Subjects treated with inhaled anti-viral therapy and washout period ≦ 48 hours. If Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) or Alkaline Phosphatase (ALP) are ≥3x ULN and Total Bilirubin (TB) is ≥2x ULN. Female subjects with positive pregnancy test result, breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug. Subjects taking any other investigational drug used to treat for another respiratory infection. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAS181 SD group Cohort 1, Stage 1<br>DAS181 SD group 4.5mg/day for 7 or 10 days | Drug: DAS181<br>* SD (4.5mg/day), HD (9mg/day)<br>|
| Experimental: DAS181 HD group Cohort 1, Stage 1<br>DAS181 HD group 9mg/day for 7 or 10 days. | Drug: DAS181<br>* SD (4.5mg/day), HD (9mg/day)<br>|
| Placebo Comparator: Placebo, Cohort 1, Stage 1<br>Placebo 0mg/day for 7 or 10 days | Drug: Placebo<br>* Placebo 0mg/day<br>|
| Experimental: DAS181 group, Cohort 1, Stage 2<br>DAS181 4.5mg/day or 9mg/day. Dosage will be determined after completion of stage 1. | Drug: DAS181<br>* SD (4.5mg/day), HD (9mg/day)<br>|
| Placebo Comparator: Placebo, Cohort 1, Stage 2<br>Placebo 0mg/day for 7 or 10 days | Drug: Placebo<br>* Placebo 0mg/day<br>|
| Experimental: DAS181 group, Cohort 2, Stage1 and 2<br>DAS181 4.5mg/day or 9mg/day for 7 or 10 days | Drug: DAS181<br>* SD (4.5mg/day), HD (9mg/day)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of subjects who have returned to room air | Percent of subjects who have returned to room air | 7 days | 
| Percent change of subjects return to baseline oxygen requirement | Percent change of subjects return to baseline oxygen requirement by Day 7 compared to Day 1 | 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Severe hospitalized influenza, Lower Respiratory Tract Disease, Acute Hypoxemia, DAS181, Ansun, infection