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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhaler that combines three medications to help people with poorly controlled asthma breathe easier. The inhaler, Trelegy Ellipta (also called FF/UMEC/VI), contains an anti-inflammatory drug and two medications that open airways, all delivered in one puff. Researchers will use special imaging to observe how well air spreads in the lungs and assess changes in lung function. Candidates for this trial have moderate to severe asthma that hasn't been well controlled despite treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for asthma.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the triple therapy inhaler containing fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) is generally well-tolerated by people with asthma. Studies indicate it offers a good balance of benefits and risks, effectively managing asthma symptoms while maintaining a strong safety record.

One study found that the inhaler reduced asthma flare-ups, which are times when symptoms suddenly worsen. Another study showed that patients who switched to this inhaler experienced better asthma control. This suggests it can be a safe option for those whose asthma is not well-managed.

While all medications can have side effects, evidence suggests that this inhaler is a safe choice for many people with asthma. Always discuss any concerns about treatment options with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

The triple therapy inhaler for asthma, combining FF (fluticasone furoate), UMEC (umeclidinium), and VI (vilanterol), is unique because it integrates three different types of medications into one device: an inhaled corticosteroid (ICS), a long-acting muscarinic antagonist (LAMA), and a long-acting beta agonist (LABA). Existing treatments typically use combinations of two of these drug types, such as ICS/LABA combinations, for asthma management. This triple therapy aims to enhance lung function and reduce asthma symptoms by addressing multiple pathways of asthma simultaneously. Researchers are excited because this approach could provide improved control for individuals with moderate to severe asthma who don't respond adequately to current treatments.

What evidence suggests that this triple therapy inhaler is effective for asthma?

Studies have shown that the triple therapy inhaler, which combines three medications, effectively treats asthma. Research indicates that this treatment reduces asthma symptoms and decreases the number of severe asthma attacks. Specifically, patients using this inhaler experienced 34% fewer severe asthma attacks compared to those on another treatment. Additionally, starting this triple therapy after other treatments was linked to fewer asthma-related issues. Overall, this inhaler has shown promise in improving control over asthma symptoms. ^{1 2 3 5 6}

Who Is on the Research Team?

Grace E Parraga, PhD

Principal Investigator

Robarts Research Institute, The University of Western Ontario

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11955660/

trelegy ellipta for real asthma control study In patients with symptomatic asthma showing insufficient control, an improvement in the asthma symptoms was observed after switching to FF-UMEC- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03376932

Vilanterol (FF/UMEC/VI) Using the Connected Inhaler ... Annualized rate of moderate/severe asthma exacerbations will be compared to evaluate the effectiveness of FF/UMEC/VI with CIS on improving asthma control ...

3. trelegyhcp.com trelegyhcp.com/copd/impact-study/

IMPACT Study Data | TRELEGY ELLIPTA (fluticasone furoate ... TRELEGY demonstrated a reduction of 13% in annual rate of severe exacerbations vs BREO (P=NS) and a significant 34% reduction vs ANORO (P<0.001).1. IMPACT study ...

4. link.springer.com link.springer.com/article/10.1007/s12325-024-03083-6

Outcomes of Patients with Asthma Treated with ICS/LABA ... Initiation of FF/UMEC/VI after ICS/LABA treatment among Medicare Advantage-insured patients with asthma was associated with reduced rates of asthma-related ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32918892/

Efficacy and safety of once-daily single-inhaler triple ... Single-inhaler FF/UMEC/VI is an effective treatment option with a favourable risk-benefit profile. Higher dose FF primarily reduced the rate of exacerbations.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03376932

Vilanterol (FF/UMEC/VI) Using the Connected Inhaler ... Annualized rate of moderate/severe asthma exacerbations will be compared to evaluate the effectiveness of FF/UMEC/VI with CIS on improving asthma control ...