Triple Therapy vs Dual Therapy for Asthma

Recruiting at 70 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must be taking: Inhaled corticosteroids, Long-acting beta2-agonists

Disqualifiers: Life-threatening asthma, Active pulmonary diseases, Smoking, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

292 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a three-drug combination improves lung function more effectively than a two-drug combination for people with asthma. The study compares two treatments: one using Fluticasone Furoate, Umeclidinium, and Vilanterol (Trelegy Ellipta), and the other using Fluticasone Furoate and Vilanterol (Breo Ellipta). The goal is to determine which treatment helps patients breathe better after 24 weeks. Teens aged 12-17 who have had asthma for at least a year and require daily inhaler use might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in asthma treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you have been on a stable asthma medication regimen for at least 6 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both treatments in this study—FF/UMEC/VI and FF/VI—are generally well-tolerated by people with asthma.

For the FF/UMEC/VI treatment, past studies indicate that patients handle it well. Some evidence even suggests it might reduce the number of severe asthma attacks. However, a possible increased risk of asthma-related hospital visits is important to consider.

The FF/VI treatment also has a good safety record. Previous studies found no major safety issues, and patients did not experience more severe or frequent side effects.

In summary, both treatments have been studied before and are generally considered safe for people. Always consult a healthcare provider to understand what this means for individual circumstances. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the FF/UMEC/VI treatment for asthma because it offers a triple therapy approach that could enhance symptom control compared to the usual dual therapies. This combination includes fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI), which together target inflammation, airway constriction, and bronchodilation. The inclusion of umeclidinium, a long-acting muscarinic antagonist, is particularly noteworthy as it adds an extra layer of bronchodilation, potentially leading to better breathing and fewer asthma attacks. While standard treatments often focus on just two components, this triple therapy aims to provide a more comprehensive management of asthma symptoms.

What evidence suggests that this trial's treatments could be effective for asthma?

Research shows that the combination of Fluticasone Furoate (FF), Umeclidinium (UMEC), and Vilanterol (VI), which participants in this trial may receive, effectively improves asthma symptoms. In earlier studies, patients who switched to FF/UMEC/VI experienced fewer asthma-related problems and had less frequent moderate to severe asthma attacks. This combination significantly reduced the yearly rate of these flare-ups compared to similar treatments.

Alternatively, FF/VI, another treatment option in this trial, also effectively manages asthma. Studies have shown that patients using FF/VI had fewer asthma flare-ups and better overall control of their symptoms over a 24-week period compared to other treatments. Both treatments have strong evidence supporting their ability to improve asthma management, with the triple therapy (FF/UMEC/VI) offering extra benefits for reducing symptoms. ^{1 5 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for 12-17 year-olds with poorly controlled asthma despite using inhaled steroids and long-acting beta agonists. They should have had a recent healthcare visit for asthma or a change in therapy, but no pneumonia or other lung diseases recently. Smokers or those with life-threatening asthma can't join.

Inclusion Criteria

My asthma is not well-controlled despite using my regular inhalers.

I've seen a doctor or changed my asthma treatment due to an attack in the last year.

My lung function is between 40% and 90% of the expected level and improves with a specific inhaler.

Exclusion Criteria

I haven't needed new asthma treatments or steroids for 3 days in the last 6 weeks.

I have not smoked or used any inhaled recreational products in the last year.

You had pneumonia shown on a chest X-ray within 6 weeks before the first visit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FF/UMEC/VI or FF/VI to evaluate effects on lung function over 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FF/UMEC/VI
• FF/VI

Trial Overview The study compares the effects of two inhalers on lung function over 24 weeks: one combines Fluticasone Furoate (FF), Umeclidinium (UMEC), and Vilanterol (VI) while the other has just FF and VI.

How Is the Trial Designed?

Group I: Participants receiving FF/UMEC/VI Experimental Treatment 2 Interventions

Group II: Participants receiving FF/VI Active Control 2 Interventions

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?

GlaxoSmithKline

Lead 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 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 the FULFIL trial involving 1810 patients with chronic obstructive pulmonary disease (COPD), the once-daily triple therapy of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) significantly reduced the rate of moderate/severe exacerbations compared to the twice-daily dual therapy of budesonide/formoterol (BUD/FOR), especially in patients with a recent history of exacerbations.

FF/UMEC/VI also led to significant improvements in lung function and health status, demonstrating its efficacy as a treatment option for COPD regardless of the patient's exacerbation history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Recent Exacerbation History on the Efficacy of Once-Daily Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease in the FULFIL Trial. Panettieri, RA., Camargo, CA., Cheema, T., 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 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]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39714547/

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 ...

3. 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 ...

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

IMPACT Study Data | TRELEGY ELLIPTA (fluticasone furoate ... TRELEGY significantly reduced the annual rate of moderate to severe exacerbations by 15% vs BREO (P<0.001) and by 25% vs ANORO (P<0.001).1. Exacerbation ...

5. 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 ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1713901

Once-Daily Single-Inhaler Triple versus Dual Therapy in ... Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10697089/

Real-World Study of Single-Inhaler Triple Therapy with ... Real-world asthma control data among patients initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) are limited.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04937387

NCT04937387 | Efficacy and Safety of Fluticasone Furoate/ ... The study aims to evaluate the efficacy, safety and tolerability of FF/UMEC/VI compared with FF/VI via ELLIPTA® inhaler in Chinese participants with ...