What side effects are associated with this type of intervention?

Common treatments for severe asthma, particularly those involving anti-IL-5 monoclonal antibodies like mepolizumab and benralizumab, can have side effects such as headache, injection site reactions, back pain, and fatigue. More serious but less common side effects include hypersensitivity reactions and increased risk of infections. Other asthma treatments, such as inhaled corticosteroids and long-acting beta-agonists, may cause oral thrush, hoarseness, and increased heart rate.

What prior FDA approvals exist?

The FDA has approved several anti-IL-5 monoclonal antibodies for the treatment of severe eosinophilic asthma. Mepolizumab (Nucala) was one of the first, approved in 2015, and works by inhibiting IL-5, reducing the production and survival of eosinophils. Benralizumab (Fasenra), approved in 2017, also targets IL-5 but works by binding to the IL-5 receptor on eosinophils, leading to their destruction. These treatments have been shown to reduce asthma exacerbations and improve control in patients with severe eosinophilic asthma.

What other types of research exist?

Promising, novel alternatives to GSK3511294 (Depemokimab) for asthma patients include mepolizumab (anti-IL-5 monoclonal antibody) and benralizumab (anti-IL-5 receptor monoclonal antibody). Additionally, other biologics targeting different pathways, such as dupilumab (anti-IL-4/IL-13 monoclonal antibody) and tezepelumab (anti-TSLP monoclonal antibody), are also promising options for asthma management.

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Monoclonal Antibodies

Depemokimab for Asthma (NIMBLE Trial)

Q: What is the mechanism of action of this treatment?

Anti-IL-5 monoclonal antibodies, such as GSK3511294 (Depemokimab), work by targeting and inhibiting interleukin-5 (IL-5), a cytokine responsible for the growth and activation of eosinophils. Eosinophils are white blood cells that play a key role in the inflammation and hyperresponsiveness seen in severe asthma with an eosinophilic phenotype. By reducing eosinophil levels, these treatments help decrease airway inflammation, reduce asthma exacerbations, and improve overall asthma control. Other common treatments include corticosteroids, which reduce inflammation broadly, and bronchodilators, which relax airway muscles to improve breathing. Understanding these mechanisms is crucial for asthma patients as it helps tailor treatments to their specific type of asthma, potentially improving outcomes and quality of life.

Verified Trial

Phase 3

Recruiting

Research Sponsored by GlaxoSmithKline

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adult and adolescent participants more than or equal to (>=)12 years of age, at the time of signing the informed consent/assent.

Participants who have a documented physician diagnosis of asthma for >=2 years that meets the National Heart, Lung, and Blood Institute guidelines (NHLBI) or Global Initiative for Asthma (GINA) guidelines.

Timeline

Screening 1 day

Treatment 52 weeks

Follow Up 3 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new medication called Depemokimab for people with severe asthma who have high levels of certain white blood cells. The goal is to see if switching to Depemokimab works as well as their current treatments. The medication aims to reduce these white blood cells to help control asthma symptoms.

Who is the study for?

Adults and adolescents (12+ years) with severe asthma who've been on medium to high dose inhalers for the past year, plus another controller medication. They must have shown improvement with Mepolizumab or Benralizumab treatments. Not for current/former heavy smokers, those with other lung conditions, cancer in remission <1 year, or certain blood disorders.

What is being tested?

The trial is testing if Depemokimab (GSK3511294) is as effective as Mepolizumab or Benralizumab in reducing asthma attacks when added to standard care. Participants will either continue their current treatment or switch to Depemokimab while maintaining their usual non-biologic asthma medications.

What are the potential side effects?

Potential side effects may include reactions at the injection site, headaches, fatigue, and possible allergic responses similar to those experienced with other biologic therapies used for asthma.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 12 years old or older and can consent to participate.

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I have been diagnosed with asthma for 2 years or more, according to NHLBI or GINA guidelines.

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I've been on mepolizumab or benralizumab for 12 months with significant improvement.

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I've been on a medium to high dose asthma inhaler for the past year.

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I am currently taking a medication in addition to my inhaled corticosteroid for my condition.

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I am using Mepolizumab or Benralizumab.

Timeline

Screening ~ 1 day1 visit

Treatment ~ 52 weeks16 visits

Follow Up ~ 3 months15 visits

Screening ~ 1 day

Treatment ~ 52 weeks

Follow Up ~3 months

This trial's timeline: 1 day for screening, 52 weeks for treatment, and 3 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Annualized rate of clinically significant exacerbations over 52 weeks

Secondary study objectives

Weighted mean change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score

Weighted mean change from Baseline in St. George's Respiratory Questionnaire (SGRQ) total score

Weighted mean change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1)

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Participants receiving GSK3511294 (Depemokimab) plus placebo matching prior anti-IL-5/5R treatmentExperimental Treatment4 Interventions

Participants will receive GSK3511294 (Depemokimab) plus placebo treatment matching the active comparator (participant's anti-Interleukin-5/ 5 receptor [anti-IL-5/5R] treatment prior to randomization): either placebo matching mepolizumab or placebo matching benralizumab. All participants will continue their non-biologic Baseline SoC asthma treatment throughout the study.

Group II: Participants receiving prior anti-IL-5/5R treatment plus placebo matching GSK3511294 (Depemokimab)Active Control5 Interventions

Participants will receive active comparator (participant's anti-IL-5/5R treatment prior to randomization): either mepolizumab or benralizumab, plus placebo matching GSK3511294 (Depemokimab). All participants will continue their non-biologic Baseline SoC asthma treatment throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

Standard of care (SoC)

2020

N/A

~20

GSK3511294 (Depemokimab)

2021

Completed Phase 3

~800

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Anti-IL-5 monoclonal antibodies, such as GSK3511294 (Depemokimab), work by targeting and inhibiting interleukin-5 (IL-5), a cytokine responsible for the growth and activation of eosinophils. Eosinophils are white blood cells that play a key role in the inflammation and hyperresponsiveness seen in severe asthma with an eosinophilic phenotype. By reducing eosinophil levels, these treatments help decrease airway inflammation, reduce asthma exacerbations, and improve overall asthma control. Other common treatments include corticosteroids, which reduce inflammation broadly, and bronchodilators, which relax airway muscles to improve breathing. Understanding these mechanisms is crucial for asthma patients as it helps tailor treatments to their specific type of asthma, potentially improving outcomes and quality of life.