Reslizumab in Patients With Severe Asthma Who Failed to Respond to Omalizumab

Reslizumab in Patients With Severe Asthma Who Failed to Respond to Omalizumab: a Pilot Study

Approximately, 5% of the patients with asthma suffer a difficult-to-control severe variant of the disease. Despite being treated with inhaled corticosteroids (ICs), long-acting β2-agonists (LABA), oral corticosteroids or omalizumab, one or more components of the control concept (symptoms, exacerbations, bronchial obstruction) remain to be resolved. Omalizumab has been proven to safely reduce asthma exacerbations and to decease symptoms and quality of life in severe allergic asthmatics. However, approximately 25% of the treated patients fail to respond to this monoclonal antibody. The rest of them show different degrees of response, although the rate of asthmatics who achieve control of the disease is unknown because clinical trials of omalizumab have been carried out to assess the impact of the drug on exacerbations, symptoms or even pulmonary function, but its effect on control was not evaluated. Therefore, there is a need to find new therapeutic options for those severe asthmatics who remain uncontrolled despite having received all the recommended therapies (including omalizumab). Reslizumab is a humanized anti-interleukin-5 (IL-5) monoclonal antibody (mAb) that has been recently found to reduce exacerbations and to improve pulmonary function and symptoms in patients with severe asthma and high peripheral eosinophil counts. It would be important to demonstrate that Reslizumab is able to improve the clinical condition of severe asthma patients with no therapeutic options.

Study Overview

• Status: Completed
• Conditions: Severe Asthma
• Intervention / Treatment: Drug: Reslizumab

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Córdoba, Spain, 14004
    • Hospital Reina Sofia
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Sevilla, Spain, 41013
    • Hospital Virgen Del Rocio
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Hospital de Sabadell
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Hospital Universitario de Cruces
  • Islas Baleares
    • Palma, Islas Baleares, Spain, 07120
      • Hospital Universitari Son Espases
  • Vizcaya
    • Galdakao, Vizcaya, Spain, 48960
      • Hospital Galdakao-Usansolo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients between 18 and 70 years of age,
• Patients diagnosed with severe uncontrolled asthma
• Patients who give informed consent.
• Previous treatment with omalizumab that was discontinued because lack of efficacy (symptoms -ACT <20, exacerbations) or adverse effects.
• Patients with a high blood eosinophil count (400 μl) at least once in the previous 3 years.
• Women should be surgically sterilized, at least 2 years have passed since menopause, or must have a negative pregnancy test within 7 days prior to initiation of treatment.
• Women of childbearing potential (not surgically sterilized or menopausal for less than 2 years) should use a medically accepted method of contraception and should agree to continue using this method during the study and at least 30 days after the end of the study.
• Patient should be willing and able to comply with the study restrictions and attend the visits indicated in the protocol to carry out the follow-up evaluations detailed in the protocol.

Exclusion Criteria:

• Diagnosis of asthma-COPD (Chronic Obstructive Pulmonary Disease) overlap syndrome.
• Active and former smokers of>10 packages / year.
• Exacerbations during the previous 4 weeks.
• Current treatment with omalizumab or last dose of omalizumab in the 5 months prior to inclusion of the patient in the study. 5- Exposure to another monoclonal antibody.
• Participation in another clinical trial.
• Uncontrolled clinically significant disease, which may interfere with study procedures, interpretation of efficacy results, or compromise patient safety.
• Underlying lung disorder.
• Known hypereosinophilic syndrome.
• A pregnant or lactating woman, or who intends to become pregnant during the study.
• Participation in a clinical trial within 30 days prior to the start of treatment.
• Previous exposure to reslizumab or other anti-IL-5 monoclonal antibody.
• Immunodeficiency disorder, including HIV.
• Suspected drug or alcohol abuse.
• Active helminth parasite infection or for which treatment was received in the 6 months prior to the start of treatment.
• History of allergic reaction or hypersensitivity to any component of the study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reslizumab; Reslizumab 3 mg/kg once / every 4 weeks during 24 weeks	Drug: Reslizumab; Reslizumab 3 mg/kg once / every 4 weeks during 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Asthma Control Test score (ACT)	Change in Asthma Control Test score (ACT) between baseline and week 24.	Baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Asthma Control Test (ACT) score	Change in ACT between baseline and week 12	Baseline and 12 weeks
Change from baseline in the 7-item Asthma Control Questionnaire (ACQ).	Change in the 7-item ACQ between baseline and week 24.	Baseline and 24 weeks
Percentage of patients that achieve the minimally important difference in ACT	Percentage of patients that achieve the minimally important difference in ACT (increase of at least 3 ponints) at week 24	Baseline and 24 weeks
Percentage of patients that achieve the minimally important difference in ACQ-7	Percentage of patients that achieve the minimally important difference in ACQ-7 (reduction of at least 0.5 ponints) at week 24	Baseline and 24 weeks
Change from baseline in eosinophil count in peripheral blood.	Change from baseline in eosinophil count in peripheral blood at week 24.	Baseline and 24 weeks
Change from baseline in lung function (FEV1).	Change from baseline in lung function (FEV1) at week 24.	Baseline and 24 weeks
Number of severe exacerbations of asthma.	Number of severe exacerbations of asthma during the 24 weeks of the study.	24 weeks
Change from baseline in the Asthma Quality of Life Questionnaire (AQLQ) score.	Change from baseline in the AQLQ questionnaire score at week 24.	Baseline and 24 weeks
Change from baseline in exhaled nitric oxide levels.	Change from baseline in exhaled nitric oxide levels at week 24.	Baseline and 24 weeks
Number of participants with adverse events	Number of participants with adverse events	24 weeks
Number of participants with severe adverse events	Number of participants with severe adverse events	24 weeks

Collaborators and Investigators

• Sponsor: Sociedad Española de Neumología y Cirugía Torácica
• Collaborators: Teva Pharmaceuticals USA
• Investigators: Study Director: Luis Pérez de Llano, MD, Hospital Universitario Lucus Augusti

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): March 26, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 3, 2017
• First Posted (Actual): March 9, 2017

Study Record Updates

• Last Update Posted (Actual): May 16, 2018
• Last Update Submitted That Met QC Criteria: May 10, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Reslizumab
• Other Study ID Numbers: SEP-RES-2016-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No