Effect of Inhaled TD-8236 on Allergen-induced Asthmatic Response

A Randomized, Double-blind, Placebo-controlled, 3-period Crossover Study to Evaluate the Effects of Repeated Doses of Inhaled TD-8236 and Impact on Airway Responses Following Allergen Challenge in Patients With Asthma

This will be a randomized, double-blind, placebo-controlled study. The study will use a three-period, six-sequence, complete-block, cross-over study design to characterize two doses of inhaled TD-8236 compared to placebo in subjects with mild asthma and a known response to an allergen. Each of the three periods will be 14 days, followed by a washout period before the next period.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: TD-8236; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W1G 8HU
    • Theravance Biopharma Investigational Site
  • Manchester, United Kingdom, M23 9QZ
    • Theravance Biopharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, 18 to 65 years of age
• Willing and able to give informed consent and comply with study requirements
• Documented physician-diagnosed asthma for ≥ 4 months prior to Screening
• Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 at Screening and weighs ≥ 50 kg at Screening.
• Women of child bearing potential must have a negative pregnancy test
• Males and females must use a highly efficient birth control method
• Pre-bronchodilator FEV1 ≥ 70% predicted
• Documented allergy to at least one common allergen
• Dual responder to inhaled bronchial challenges
• Additional inclusion criteria apply

Exclusion Criteria:

• Positive for hepatitis A, B or C, HIV or tuberculosis
• Clinically significant abnormalities of laboratory evaluations
• Have abnormal ECG measurements
• Any sign of respiratory tract infection within 6 weeks of screening
• Have a current bacterial, parasitic, fungal or viral infection
• History of life-threatening asthma
• Uses or have used tobacco or nicotine-containing products 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: CROSSOVER
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TD-8236 Dose A (low dose); TD-8236 Dose A (QD x 14 days)	Drug: TD-8236; The study drug will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods.
EXPERIMENTAL: TD-8236 Dose B (high dose); TD-8236 Dose B (QD x 14 days)	Drug: TD-8236; The study drug will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods.
PLACEBO_COMPARATOR: Placebo; Placebo (QD x 14 days)	Drug: Placebo; The placebo will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve of Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14	Values are reported as a weighted mean derived by calculating the AUC change from baseline over the relative time interval, divided by the time interval.	Day 14 of treatment period: 3 to 8 hours after allergen challenge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve of Percentage Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14	Values are reported as a weighted mean derived by calculating the AUC percentage change from baseline over the relative time interval, divided by the time interval.	Day 14 of treatment period: 3 to 8 hours after allergen challenge
Maximum Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14		Day 14 of treatment period: 3 to 8 hours after allergen challenge
Maximum Percentage Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14		Day 14 of treatment period: 3 to 8 hours after allergen challenge
Area Under the Concentration-time Curve Over One 24-hour Dosing Interval (AUC0-24) of TD-8236 in Plasma		Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of TD-8236 in Plasma During Dosing Interval		Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
Time to Maximum Observed Concentration (Tmax) of TD-8236 in Plasma Over a Dosing Interval		Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)	A TEAE was defined as any adverse event (AE) that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus the number of days in the follow-up period. The severity of TEAEs were also assessed and were classified as mild, moderate or severe per the definitions below: Mild - The AE is noticeable to the participant and/or the investigator, but does not interfere with routine activity. Moderate - The AE interferes with routine activity, but responds to symptomatic therapy or rest. Severe - The AE significantly limits the participant's ability to perform routine activities despite symptomatic therapy.	Day 1 to end of follow-up (up to approximately 98 days)

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 6, 2019
• Primary Completion (ACTUAL): August 28, 2020
• Study Completion (ACTUAL): September 3, 2020

Study Registration Dates

• First Submitted: October 15, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (ACTUAL): November 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Asthma; Proof of concept; TD-8236
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 0178; 2019-002915-24 (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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes