Triple Therapy Inhaler for Asthma

(ETHA Trial)

Overseen By Angela P Wilson, RRT

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Dr. Grace Parraga

Must be taking: Inhaled corticosteroids, LABA

Disqualifiers: Pulmonary disease, Cardiovascular, Neurological, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

31 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a combination of three medications to help adults with poorly controlled asthma. The medications work together to reduce lung inflammation and open airways, making it easier to breathe. One of the medications is being tested in combination with others to improve asthma control in patients who do not respond well to usual treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have been on a stable dose of certain asthma medications for at least 6 months before joining. If you are on biologic therapy, a washout period (time without taking the medication) is required before screening.

What data supports the effectiveness of the drug Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol) for asthma?

The drug Trelegy Ellipta, which combines fluticasone furoate, umeclidinium, and vilanterol in a single inhaler, is approved for asthma maintenance treatment. Although specific real-world data on its effectiveness for asthma is limited, it has been approved for chronic obstructive pulmonary disease (COPD), suggesting its potential effectiveness in managing respiratory conditions. ^{1 2 3 4 5}

Is the triple therapy inhaler FF/UMEC/VI safe for humans?

The triple therapy inhaler FF/UMEC/VI has been studied for safety in both patients with COPD and healthy volunteers. Studies have shown that the drug concentrations in the body are similar to those seen with individual or dual therapies, and it has been approved by the FDA for COPD, indicating a recognized safety profile. ^{2 3 4 5 6}

How is the drug Trelegy Ellipta different from other asthma treatments?

Trelegy Ellipta is unique because it combines three medications (fluticasone furoate, umeclidinium, and vilanterol) into a single inhaler, making it more convenient than using multiple inhalers. This triple therapy is designed for patients whose asthma is not well-controlled with standard dual therapy. ^{1 2 3 4 5}

Research Team

Grace E Parraga, PhD

Principal Investigator

Robarts Research Institute, The University of Western Ontario

Eligibility Criteria

Adults aged 18-70 with poorly controlled eosinophilic asthma, using long-acting β2-agonists for at least 6 months. Must not smoke or vape, have a history of less than one pack-year tobacco use, and no significant exacerbations in the last month. Women must use effective birth control and have a negative pregnancy test.

Inclusion Criteria

Your ACQ-6 score is 1.5 or higher at the first visit.

I have had 2 or more asthma attacks in the last 2 years.

I have been on a stable dose of certain asthma medications for at least 6 months.

Exclusion Criteria

I cannot perform the breathing test required.

You have participated in a study for a specific medication called FF/UMEC/VI 200/62.5/25ug before.

I have not been hospitalized or had major surgery, trauma, or illness in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline

Baseline assessments including CT and MRI scans, and pulmonary function tests

1 day

1 visit (in-person)

Treatment

Participants receive triple therapy with FF/UMEC/VI for 6 weeks, with MRI and pulmonary function tests

6 weeks

3 visits (in-person), 1 optional visit (in-person or phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (phone call)

Treatment Details

Interventions

• FF/UMEC/VI

Trial Overview The trial tests triple therapy inhaler (FF/UMEC/VI) effectiveness on asthma control by assessing lung function through MRI with xenon gas contrast, CT scans, spirometry, and questionnaires to measure air distribution in lungs compared to standard treatments.

Participant Groups

Group I: Participants with poorly controlled moderate to severe asthma Experimental Treatment 1 Intervention

Participants with poorly controlled moderate to severe asthma will be evaluated during and after a six week trial of triple therapy (ICS/LABA/LAMA) for changes in 129Xe MRI ventilation percent defect, pulmonary function measurements.

FF/UMEC/VI is already approved in United States for the following indications:

Approved in United States as Trelegy Ellipta for:

• Chronic Obstructive Pulmonary Disease (COPD)
• Asthma

Who Is Running the Clinical Trial?

Dr. Grace Parraga

Lead Sponsor

Trials

6

Recruited

490+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a study of 6,511 patients, those using the single-inhaler triple therapy FF/UMEC/VI showed significantly better adherence to their medication compared to those using multiple inhalers, with a mean proportion of days covered of 0.68 versus 0.59.

Patients on FF/UMEC/VI were also 49% more likely to continue their treatment after 12 months compared to those on multiple-inhaler therapy, indicating that the single-inhaler option may improve long-term treatment persistence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence and Persistence to Single-Inhaler Versus Multiple-Inhaler Triple Therapy for Asthma Management. Busse, WW., Abbott, CB., Germain, G., et al.[2022]

In a study of 22,177 COPD patients, most users of the single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and multiple-inhaler triple therapy (MITT) had experienced moderate to severe exacerbations or were already on maintenance therapy before starting treatment, indicating a need for more effective management of their condition.

The study found that a significant portion of FF/UMEC/VI users (41.2%) had previously used overlapping inhaler therapies, suggesting that patients often transition to this therapy after inadequate control with existing medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient and Clinical Demographics of New Users to Single-Inhaler Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease. Wu, B., Mannino, D., Mu, G., et al.[2022]

A population pharmacokinetic analysis of 74 patients with COPD showed that the combined inhaler of fluticasone furoate, umeclidinium, and vilanterol delivers drug concentrations similar to those seen with individual or dual therapies, indicating effective absorption and distribution.

The study, part of a 24-week trial comparing triple therapy to dual therapy, suggests that the once-daily triple therapy is pharmacokinetically comparable to existing treatments, supporting its potential efficacy in managing COPD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium/Vilanterol via a Single Inhaler in Patients with COPD. Mehta, R., Pefani, E., Beerahee, M., et al.[2019]

In the 52-week IMPACT study involving 7012 patients with chronic obstructive pulmonary disease (COPD), single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) showed similar cardiovascular (CV) safety compared to dual therapies (FF/VI and UMEC/VI), with CV adverse events occurring in 10-11% of patients across all treatment groups.

There was no statistically significant increase in cardiovascular risk associated with FF/UMEC/VI compared to the other therapies, indicating that this triple therapy is safe for patients with COPD who have a high prevalence of cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial. Day, NC., Kumar, S., Criner, G., et al.[2021]

In two studies involving 88 healthy volunteers, the closed triple therapy of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) showed similar systemic exposure to its components compared to dual therapies, indicating effective delivery of the medication.

The safety profile was favorable, with a low incidence of adverse events across all treatment groups, suggesting that the triple therapy can be safely administered without significant systemic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol as a triple therapy in healthy volunteers. Brealey, N., Gupta, A., Renaux, J., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adherence and Persistence to Single-Inhaler Versus Multiple-Inhaler Triple Therapy for Asthma Management. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Patient and Clinical Demographics of New Users to Single-Inhaler Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium/Vilanterol via a Single Inhaler in Patients with COPD. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol as a triple therapy in healthy volunteers. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily, single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol in Japanese patients with inadequately controlled asthma: the CAPTAIN study. [2021]