Benralizumab for COPD

(RESOLUTE Trial)

Recruiting at 332 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 56 weeks

689 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 3 study to evaluate the efficacy and safety of a benralizumab in patients with moderate to very severe COPD with a history of frequent COPD exacerbations and elevated peripheral blood eosinophils (≥300/μL). Eligible patients must have a history of ≥2 moderate and/or severe COPD exacerbations in the previous year despite receiving triple (ICS/LABA/LAMA) background therapy for at least 3 months and ICS-based dual inhaled treatment for the remainder of the year. Eligible patients must also have an elevated blood eosinophil count. The treatment period will be of variable duration and will continue until the last patient has the opportunity to complete a minimum of 56 weeks, at which point all patients will complete the study. The primary endpoint will be analyzed at Week 56.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. In fact, it requires that you continue your existing COPD treatment (triple therapy) for at least 3 months before joining the study.

What data supports the effectiveness of the drug benralizumab for COPD?

Benralizumab has been approved for treating severe eosinophilic asthma, which shares some characteristics with certain types of COPD, such as eosinophilia (high levels of a type of white blood cell). However, studies like GALATHEA and TERRANOVA did not show a significant reduction in COPD exacerbations with benralizumab compared to a placebo. ^{1 2 3 4 5}

Is benralizumab safe for humans?

Benralizumab has been approved for use in humans as a treatment for severe eosinophilic asthma, indicating it has undergone safety evaluations. While its safety for COPD specifically is still being studied, its approval for asthma suggests it is generally considered safe for human use. ^{1 2 3 5 6}

Research Team

Gerard Criner, MD

Principal Investigator

Temple University School of Medicine, 3401 North Broad Street, Suite 745 PP, Philadelphia, PA 19140

Eligibility Criteria

Adults aged 40-85 with moderate to very severe COPD, a history of frequent exacerbations despite ongoing triple therapy, and elevated blood eosinophils can join. They must have smoked at least 10 pack-years. Excluded are those with unstable disorders, other significant lung diseases like asthma, oxygen needs over 4 L/min, certain liver diseases or infections, recent use of certain drugs or biologics.

Inclusion Criteria

Total cumulative duration of not being on double or triple background therapy must not exceed 2 months

I use LABA/LAMA because I can't tolerate ICS.

I am between 40 and 85 years old.

Exclusion Criteria

I haven't taken any experimental drugs within the last 30 days or 5 half-lives.

I need more than 4 liters per minute of oxygen or my oxygen levels stay below 89% even with extra oxygen.

I use a CPAP machine for sleep apnea.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive benralizumab or placebo subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks

56 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes

up to 2 years

Treatment Details

Interventions

• Benralizumab
• Placebo

Trial Overview The trial is testing the effectiveness and safety of Benralizumab compared to a placebo in patients with COPD who frequently experience flare-ups. Participants will receive treatment for at least 56 weeks to see if it reduces these exacerbations.

Participant Groups

Group I: Benralizumab Experimental Treatment 1 Intervention

Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks

Group II: Placebo Placebo Group 1 Intervention

Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks

Benralizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Fasenra for:

• Severe eosinophilic asthma

Approved in United States as Fasenra for:

• Severe asthma with an eosinophilic phenotype

Approved in Canada as Fasenra for:

• Severe eosinophilic asthma

Approved in Japan as Fasenra for:

• Severe eosinophilic asthma

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Benralizumab (Fasenra™) is a monoclonal antibody that targets the interleukin-5 receptor alpha chain, specifically designed to treat severe eosinophilic asthma and chronic obstructive pulmonary disease (COPD).

The drug has been approved by the US FDA as an add-on maintenance therapy for patients with severe asthma characterized by eosinophilia, highlighting its efficacy in depleting eosinophils, which are linked to asthma and COPD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benralizumab: First Global Approval. Markham, A.[2022]

In a study of 441 patients with severe asthma, 19% were found to be eligible for benralizumab treatment, indicating a significant subset of patients who may benefit from this therapy.

Patients eligible for benralizumab had poorer lung function and asthma control, experiencing more frequent exacerbations and hospitalizations, highlighting the need for effective treatment options in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of patients with severe, uncontrolled, eosinophilic asthma enrolled in a French cohort. Aubier, M., Thabut, G., Fabry-Vendrand, C.[2022]

References

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

Benralizumab for the Prevention of COPD Exacerbations. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Benralizumab: First Global Approval. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Characteristics of patients with severe, uncontrolled, eosinophilic asthma enrolled in a French cohort. [2022]

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

Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies. [2020]

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

Does benralizumab effectively treat chronic obstructive pulmonary disease? A protocol of systematic review and meta-analysis. [2022]

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

Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. [2022]