First in Human SAD and MAD Study of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19

Study Overview
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Brief Summary
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This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.

Official Title
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A Phase 1, Double-blind, Randomized, Placebo-controlled, Sponsor-open, SAD and MAD Study in Healthy Subjects to Evaluate the Safety, Tolerability, and PK of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19

Conditions
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Acute Lung Injury (ALI) Associated With COVID-19, Inflammatory Lung Conditions Associated With COVID-19

Intervention / Treatment
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* Drug: TD-0903
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening and weighs at least 50 kg. Medically healthy with no clinically significant medical history, physical examination, spirometry, vital signs or ECGs. Forced expiratory volume in 1 second (FEV1) ≥80%. No clinically significant abnormalities in the results of laboratory evaluations. Female subjects must be either of non-childbearing potential or if of childbearing potential, subject must not be pregnant or breastfeeding, and must agree to use a highly effective birth control method. Male subjects must agree to use condoms, in addition to the use of highly effective pregnancy prevention measures with female partners of childbearing potential. Understands the correct technique for the use the nebulizer device(s). Other inclusion criteria apply Exclusion Criteria: History or presence of clinically significant medical or psychiatric condition. Abnormal ECG measurements at Screening. Any signs of respiratory tract infection within 6 weeks of Screening. Subject who has a current bacterial, parasitic, fungal, or viral infection; any infection requiring hospitalization or intravenous antibiotics within 6 months prior to Screening. Positive test for SARS-CoV-2 Subject has any condition of the oro-laryngeal or respiratory tract. Uses or has used tobacco or nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, patches etc.) within 6 months prior to screening Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: double-blind, randomized, placebo-controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TD-0903 for SAD (Part A)<br>6 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive TD-0903 | Drug: TD-0903<br>* Study drug to be administered by inhalation<br>|
| Experimental: Placebo for SAD (Part A)<br>2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo | Drug: Placebo<br>* Placebo to be administered by inhalation<br>|
| Experimental: TD-0903 for MAD (Part B)<br>8 out of 10 subjects per cohort (up to 3 cohorts) will be randomized to receive TD-0903 | Drug: TD-0903<br>* Study drug to be administered by inhalation<br>|
| Experimental: Placebo for MAD (Part B)<br>2 out of 10 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo | Drug: Placebo<br>* Placebo to be administered by inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of SAD of TD-0903: Adverse Events | Number and severity of treatment emergent adverse events | Day 1 to Day 8 | 
| Safety and Tolerability of MAD of TD-0903: Adverse Events | Number and severity of treatment emergent adverse events | Day 1 to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC | Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC) | Day 1 through Day 4 | 
| Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax | Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax) | Day 1 through Day 4 | 
| Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax | Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax) | Day 1 through Day 4 | 
| Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC | Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC) | Day 1 through Day 9 | 
| Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax | Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax) | Day 1 through Day 9 | 
| Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax | Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax) | Day 1 through Day 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute lung injury, ALI, COVID-19, Coronavirus Disease 2019, inflammatory lung conditions, Inflammatory lung disease