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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Lung Injury (ALI) Associated With COVID-19; Inflammatory Lung Conditions Associated With COVID-19
• Intervention / Treatment: Drug: TD-0903; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • Theravance Biopharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2020
• Primary Completion (Actual): June 24, 2020
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Coronavirus Disease 2019; ALI; Acute lung injury; inflammatory lung conditions; Inflammatory lung disease
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Wounds and Injuries; Thoracic Injuries; COVID-19; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 0183; 2020-000577-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No