A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection or Severed Community Acquired Pneumonia

Study Overview
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Brief Summary
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The purpose of this study is to determine if an investigational drug, AT-100, is safe and tolerated by adults who have severe corona virus disease 2019 (COVID-19) or respiratory failure secondary to severe community acquired pneumonia.

Official Title
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Phase 1b Open-label, Single Arm, Cohort Dose Escalation Study Evaluating the Safety, Tolerability, and Feasibility of Intervention With AT-100 (rhSP-D) in Intubated Patients Receiving Invasive Mechanical Ventilation With Severe COVID-19 Infection or Respiratory Failure Secondary to Severe Community Acquired Pneumonia

Conditions
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COVID-19, Undefined

Intervention / Treatment
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* Biological: AT-100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is an adult ≥18 years of age. The subject has documented, laboratory-confirmed SARS-CoV-2 infection within 2 weeks prior to enrollment, or meets criteria for severe community acquired pneumonia (CAP) specified in inclusion 3 below. The subject has severe SARS-CoV-2 infection requiring intubation and mechanical ventilation. Or, the subject is admitted for severe CAP with respiratory failure as demonstrated by the following: 3. i. Respiratory failure requiring intubation and mechanical ventilation, and 3. ii. A clinical diagnosis of CAP that includes radiographic findings of new pulmonary infiltrate(s) consistent with CAP plus any one of the following on admission to the hospital: 3. ii. 1. Fever (Temperature > 38.0°C), 3. ii. 2. Hypothermia (Temperature < 36.0°C), 3. ii. 3. Leukocytosis with White Blood Cells (WBC) > 10,000 cells/µL or immature band forms > 10%, 3. ii. 4. Leukopenia with WBC < 4,000 cells/µL, or 3. ii. 5. Hypotension Mean Arterial Pressure (MAP) < 70 mmHg, requiring the initiation of vasopressor support. 4. The subject has been receiving mechanical ventilation for <72 hours. 5. The subject is receiving mechanical ventilation due to respiratory disease that is primarily due to SARS-CoV-2 infection or CAP. 6. The subject, or legally authorized representative if acting on the subject's behalf, is able to provide informed consent. Exclusion Criteria: The subject refuses to participate, or the subject's legally authorized representative acting on the subject's behalf refuses the subject's participation. The subject is pregnant or breastfeeding. The subject is anticipated to be transferred to another hospital that is not a study site within 36 hours of enrollment. The subject has received or is receiving extracorporeal membrane oxygenation (ECMO) treatment for COVID-19 or CAP treatment. The subject has Human Immunodeficiency virus (HIV) under highly active antiretroviral therapy (HAART). The subject has cancer and is receiving chemotherapy treatment at any time during trial duration, or has received chemotherapy treatment within 30 days of trial enrollment. The subject has a prior history of lung transplant, lobectomy, or other significant lung surgeries that would indicate an already compromised lung. The subject has known pulmonary air leaks, such as pneumothorax and pneumomediastinum. Concurrent enrollment in an investigational product, device, or treatment trial or is projected to participate in any other trial that alters the standard of care during the period of this study The subject has a known allergy, sensitivity, or contraindication to any component of the test article (AT-100). The subject has any active do not resuscitate (DNR)-Comfort Care (CC) order in place. Subjects with an active DNR-Comfort Care Arrest (CCA) are not excluded. The subject's intubation, re-intubation, or remaining on intubation is not per clinical standard-of-care and is solely for the purposes of administration of study drug. The subject has any condition or is in a situation in which, in the Investigator's judgement, puts the subject at significant risk, could confound the trial results, or may significantly interfere with the subject's trial participation.

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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase 1b portion is a dose escalation study to establish the safest & most tolerable AT-100 dose.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AT-100 75 mg<br>Once daily AT-100 via intratracheal administration for up to 7 doses. | Biological: AT-100<br>* reconstituted AT-100 for intratracheal administration<br>* Other names: (rhSP-D);|
| Experimental: AT-100 150 mg<br>Once daily AT-100 via intratracheal administration for up to 7 doses, if the prior dose level was safe & tolerated. | Biological: AT-100<br>* reconstituted AT-100 for intratracheal administration<br>* Other names: (rhSP-D);|
| Experimental: AT-100 75 mg or 150 mg (Optional Cohort)<br>Once daily AT-100 via intratracheal administration for up to 7 doses, at the highest safe & tolerated dose as determined by the prior 2 dosing levels. | Biological: AT-100<br>* reconstituted AT-100 for intratracheal administration<br>* Other names: (rhSP-D);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determining the highest-tolerated & safety-tested AT-100 dose | Dose escalation of AT-100 will occur to determine the maximum dose (in mg) that produces no significant Dose Limiting Toxicities or dose-related Adverse Events (AEs). | From time of initial AT-100 dosing until the end of the dosing period, up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in mechanical ventilation | Days on mechanical ventilation. | From mechanical ventilation initiation up to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAP, COVID-19, Mechanical Ventilation, Respiratory Support, recombinant human Surfactant Protein-D (rhSP-D), Community-acquired Pneumonia, zelpultide alfa