Selective β2-AR Antagonism in Asthma

NCT07272135 | Completed Phase 1

• 1 other identifier: T-030
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives are to assess the safety, tolerability and effect on the airways of TR4 in patients with mild-to-moderate asthma. The Phase 1 trial is randomised, double-blind, placebo-controlled, and ascending-dose in design.

Conditions

Asthma

Outcome Measures

Primary Outcomes (22)

• Mannitol (PD15)

  The dose of mannitol causing a 15% fall in FEV1

  Baseline (day -1) of treatment periods 1 to 5.

• Mannitol (PD15)

  The dose of mannitol causing a 15% fall in FEV1

  Day 21 of treatment period 5.

• Spirometry (FEV1)

  Lung function test: The forced expiratory volume in 1 second (FEV1).

  Day 1 of treatment periods 1 to 5.

• Spirometry (FEV1)

  Lung function test: The forced expiratory volume in 1 second (FEV1).

  Day 2 of treatment periods 1 to 5.

• Spirometry (FEV1)

  Lung function test: The forced expiratory volume in 1 second (FEV1).

  Day 21 of treatment period 5.

• Spirometry (FVC)

  Lung function test: forced vital capacity (FVC)

  Day 1 of treatment periods 1 to 5

• Spirometry (FVC)

  Lung function test: forced vital capacity (FVC).

  Day 2 of treatment periods 1 to 5

• Spirometry (FVC)

  Lung function test: forced vital capacity (FVC).

  Day 21 of treatment period 5

• Spirometry (FEF 25-75)

  Lung function test: forced mid-expiratory flow (FEF 25-75) is the mean forced expiratory flow during the middle half of the FVC.

  Day 1 of treatment periods 1 to 5

• Spirometry (FEF 25-75)

  Lung function test: the forced mid-expiratory flow (FEF 25-75) is the mean forced expiratory flow during the middle half of the FVC.

  Day 2 of treatment periods 1 to 5

• Spirometry (FEF 25-75)

  Lung function test: forced mid-expiratory flow (FEF 25-75) is the mean forced expiratory flow during the middle half of the FVC

  Day 21 of treatment period 5.

• Spirometry (FEV1/FVC)

  Lung function test: FEV1 as a percentage of FVC (FEV1/FVC).

  Day 1 of treatment periods 1 to 5.

• Spirometry (FEV1/FVC)

  Lung function test: FEV1 as a percentage of FVC (FEV1/FVC).

  Day 2 of treatment periods 1 to 5.

• Spirometry (FEV1/FVC)

  Lung function test: FEV1 as a percentage of FVC (FEV1/FVC).

  Day 21 of treatment period 5.

• Impulse oscillometry (IOS) (R5, R5-R20)

  Lung function test: A Jaeger impulse oscillometer will be used to obtain measurements according to the investigators standard operating procedure (SOP) and a published algorithm. The following settings will be used for IOS: oscillometric pressure impulses will be superimposed onto the tidal breathing of the subject, for about 30 s, with a pulse sequence of 5 per second and a frequency spectrum between 5 and 35 Hz. Resistance (R) at 5-20 Hz (R5 and R5-R20) during normal tidal breathing will be measured.

  Change between baseline (day -1) and day 1 of treatment periods 1 to 5.

• IOS (R5, R5-R20)

  Lung function test: A Jaeger impulse oscillometer will be used to obtain measurements according to the investigators SOP and a published algorithm. The following settings will be used for IOS: oscillometric pressure impulses will be superimposed onto the tidal breathing of the subject, for about 30 s, with a pulse sequence of 5 per second and a frequency spectrum between 5 and 35 Hz. Resistance (R) at 5-20 Hz (R5 and R5-R20) during normal tidal breathing will be measured.

  Day 21 of treatment period 5.

• IOS (AX)

  Lung function test: A Jaeger impulse oscillometer will be used to obtain measurements according to the investigators SOP and a published algorithm. The following settings will be used for IOS: oscillometric pressure impulses will be superimposed onto the tidal breathing of the subject, for about 30 s, with a pulse sequence of 5 per second and a frequency spectrum between 5 and 35 Hz. Reactance (X) at 5-20 Hz (AX) during normal tidal breathing will be measured.

  Change between baseline (day -1) and day 1 of treatment periods 1 to 5.

• IOS (AX)

  Lung function test: A Jaeger impulse oscillometer will be used to obtain measurements according to the investigators SOP and a published algorithm. The following settings will be used for IOS: oscillometric pressure impulses will be superimposed onto the tidal breathing of the subject, for about 30 s, with a pulse sequence of 5 per second and a frequency spectrum between 5 and 35 Hz. Reactance (X) at 5-20 Hz (AX) during normal tidal breathing will be measured.

  Day 21 of treatment period 5.

• Airway nitric oxide (FeNO)

  FeNO will be measured using the NIOX Viro handheld electronic device.

  Change between baseline (day -1) and day 1 of treatment periods 1 to 5.

• Airway nitric oxide (FeNO)

  FeNO will be measured using the NIOX Viro handheld electronic device.

  Day 21 of treatment period 5.

• Blood eosinophils

  Blood eosinophils concentration will be used as an inflammatory marker.

  Day -1 of treatment periods 1 to 5.

• Blood eosinophils

  Blood eosinophils concentration will be used as an inflammatory marker.

  Day 21 of treatment period 5.

Secondary Outcomes (16)

• Vital signs (safety): Blood pressure

  Day 1 and 2 of treatment periods 1 to 5. Day 21 and 22 of treatment periods 3 to 5.

• Vital signs (safety): Heart rate

  Day 1 and 2 of treatment periods 1 to 5. Day 21 and 22 of treatment periods 3 to 5.

• Vital signs (safety): Respiratory rate

  Day 1 and 2 of treatment periods 1 to 5. Day 21 and 22 of treatment periods 3 to 5.

• Vital signs (safety): Oral temperature

  Day 1 and 2 of treatment periods 1 to 5. Day 21 and 22 of treatment periods 3 to 5.

• Safety tests of blood and urine

  Day 1 of treatment periods 1 to 5 and day 22 of treatment periods 3 to 5.

Other Outcomes (3)

• Plasma TR4 and metabolite concentration

  Blood samples (4 mL) will be taken on day 1 of treatment periods 1 to 5.

• Plasma annexin-A1

  Blood samples (5 mL) will be taken on day -1 of treatment periods 1 to 5 and day 21 of treatment period 5.

• Lymphocyte beta-2-adrenoceptor density

  Blood samples (8 mL) will be taken on day -1 of treatment periods 1 to 5 and day 21 of treatment period 5.

Study Arms (2)

TR4

EXPERIMENTAL

After a run-in period of 2 weeks, 9 patients will be randomly assigned to the TR4 treatment arm. These 9 patients will take incremental doses of 2.5, 5, 10, and 20 mg of TR4, each dose three times daily for 7 days, and then 40 mg three times daily for 21 days, over a total period of 7 weeks.

Drug: TR4

Placebo

PLACEBO COMPARATOR

Three patients will take matching placebo capsules in a similar manner to TR4.

Other: Placebo

Interventions

TR4 DRUG

TR4 is a selective beta-2-adrenoceptor antagonist. TR4 will be weighed into opaque capsules and released for individual patients, in accordance with good manufacturing practice (GMP).

TR4

Placebo OTHER

Placebo capsules will contain start in opaque capsules.

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women
• Minimum 21 years old
• History of mild-to-moderate asthma for at least 6 months and controlled by an inhaled SABA, as required
• Otherwise healthy
• Ideally have participated in previous asthma studies
• No corticosteroid for whatever reason within 8 weeks of the start of dosing
• No other prescription medicine within 28 days (apart from a short acting beta-agonist (SABA) or contraceptives in women)
• No over-the-counter medicine within 7 days (apart from acetaminophen) before the start of dosing
• Negative screen for drugs of abuse; forced expiratory volume in 1 second (FEV1) more than or equal to 70% predicted
• Fractional exhaled nitric oxide (FeNO) more than or equal to 35 ppb
• % fall in FEV1 after inhaled mannitol (PD15)
• Non-smoker or past smoker (\<5 pack years)
• Substitution of subject's SABA inhaler with an anti-cholinergic inhaler, ipratropium bromide, for use as a reliever or rescue medication during a run-in period and during dosing with TR4 or placebo.

You may not qualify if:

• Positive test for hepatitis B \& C or HIV
• Drug or alcohol abuse
• Airway infection or asthma exacerbation in the last 4 weeks
• Current seasonal asthma
• History of emergency treatment of asthma
• Loss of more than 400 mL blood, or participation in other clinical trials of unlicensed medicines within the previous 3 months
• Consumption of grapefruit or herbal remedies within the past 7 days
• Objection by the subject's general practitioner (GP)
• Subjects who are sexually active and not using reliable contraception
• Women who are lactating, pregnant or plan to become pregnant during the study period
• Positive polymerase chain reaction (PCR) test for SARS-CoV-2 virus
• Subjects who have not received both doses of a COVID-19 vaccine.

Sponsors & Collaborators

• Trio Medicines Ltd.: lead
• Hammersmith Medicines Research: collaborator

Study Sites (1)

Hammersmith Medicines Research

London, London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Denisa Wilkes

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Phase 1 trial is randomised, double-blind, placebo-controlled, and ascending-dose in design.

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: December 9, 2025
• Study Start: February 28, 2018
• Primary Completion: August 16, 2022
• Study Completion: August 16, 2022
• Last Updated: December 9, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)