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Benralizumab Efficacy in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (GALATHEA)

Primary Purpose

Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Benralizumab Arm A

Benralizumab Arm B

Placebo

About this trial

This is an interventional treatment trial for Moderate to Very Severe Chronic Obstructive Pulmonary Disease focused on measuring Obstructive Lung Diseases, Chronic Obstructive Pulmonary Disease, Lung Disease, Bronchial Diseases, COPD Exacerbation, Respiratory Tract Diseases

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

2. Any disorder or major physical impairment that is not stable by Investigator opinion and/or could affect: - subject safety-study findings or their interpretation or subject's ability to complete the entire study duration.

3. Unstable ischemic heart disease, arrhythmia, cardiomyopathy, or other relevant cardiovascular disorder that in Investigator's judgment may put the patient at risk or negatively affect the study outcome.

4. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 2 weeks prior to Visit1 or during the enrolment and run-in period.

5. Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 2 weeks prior to Visit1or during the enrolment and run-in period.

6. Pneumonia within 8 weeks prior to Visit1 or during the enrolment and run-in period.

7. Pregnant, breastfeeding, or lactating women. 8. Risk factors for pneumonia 9. History of anaphylaxis to any other biologic therapy. 10. Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right ventricular failure.

11. Use of immunosuppressive medication within 2 weeks prior to Visit1 and/or during the enrolment and run-in period.

12. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit 1.

13. Evidence of active tuberculosis (TB) without an appropriate course of treatment.

14. Lung volume reduction surgery within the 6 months prior to Visit 1. History of partial or total lung resection (single lobe or segmentectomy is acceptable).

15. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines.

16. Previous treatment with benralizumab. 17. Helminth parasitic infection diagnosed within 24 weeks prior to Visit 1.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Benralizumab Arm A

Benralizumab Arm B

Placebo

Arm Description

Benralizumab administered subcutaneously

Placebo administered subcutaneously

Outcomes

Primary Outcome Measures

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL

A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or Use of antibiotics; and/or An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.

Secondary Outcome Measures

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL

Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL

Pre-bronchodilator FEV1 (L) is collected at Weeks 0, 4, 8, 16, 24, 32, 40, 48, and 56. Baseline is the last non-missing value with quality (acceptable or borderline quality grade) prior to the first dose of study treatment.

Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL

SGRQ is from 50-item PRO instrument. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0 indicates the best possible health status.

Mean Change From Baseline in CAT Total Score for Patients With Baseline EOS>=220/uL

CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. Score ranges from 0 to 40 with higher scores indicative of greater COPD impact on health status.

Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL

The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.

Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL

The number of rescue medication inhalations and nebulizer treatments taken are recorded by the patient in the eDiary twice daily. Total rescue medication use is the sum of daytime and night-time use.

Mean Change From Baseline in Proportion of Nights Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL

Change from baseline to week 56 in proportion of nights awakenings due to respiratory symptoms.

Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL

Severity of EXACT-PRO for Patients With Baseline EOS>=220/uL

Duration of EXACT-PRO for Patients With Baseline EOS>=220/uL

The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while onsidering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Calculation of event duration after identification of the following five parameters: 1) onset; 2) three-day rolling average; 3) maximum observed value; 4) threshold for improvement; and 5) recovery. That is, duration of the exacerbation is the time elapse between onset and recovery of the event.

Annual EXACT-PRO Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL

The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while onsidering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Annual EXACT-PRO exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.

Number of Participants Having at Least 1 COPD Exacerbation for Patients With Baseline EOS>=220/uL

A COPD exacerbation is defined by symptomatic worsening COPD requiring systemic corticosteroids, antibiotics, or an inpatient hospitalization/death due to COPD.

Time to First COPD Exacerbation

Time to first COPD exacerbation is from the randomization date to the first occurrence of COPD exacerbation

Annual COPD Exacerbation Rate Associated With ER or Hospitalization Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL

Annual COPD exacerbations rate that result in ER or hospitalization is calculated by number of exacerbations resulting ER or hospitalization divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.

Number of Participants Had COPD-related Healthcare Encounter for Patient With Baseline EOS>=220/uL

Types of healthcare encounter: Hospitalisations (inc. intensive care and/or general care), Emergency department visits, Unscheduled outpatients visits, Home visits, Telephone calls, and ambulance transports.

Duration of Study Treatment Administration

Duration of study treatment is calculated from first dose date to last dose date + 1 day.

Serum Concentration of Benralizumab

PK serum samples were collected pre-dose at each visit.

Immunogenicity of Benralizumab

Antidrug antibody (ADA) responses such as ADA prevalence, ADA incidence, ADA persistently positive counts, etc. were presented

Full Information

NCT ID

NCT02138916

First Posted

March 26, 2014

Last Updated

June 12, 2019

Sponsor

AstraZeneca

Collaborators

MedImmune LLC

1. Study Identification

Unique Protocol Identification Number

NCT02138916

Brief Title

Benralizumab Efficacy in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History

Acronym

GALATHEA

Official Title

Randomised, Double-blind, 56 Week Placebo-controlled, Parallel Group, Multicentre, Phase 3 Study to Evaluate the Efficacy and Safety of 2 Doses of Benralizumab in Patients With Moderate to Very Severe COPD With a History of Exacerbations

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

June 13, 2014 (Actual)

Primary Completion Date

April 10, 2018 (Actual)

Study Completion Date

April 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

MedImmune LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of the study is to determine if benralizumab reduces COPD exacerbation rate in symptomatic patients with moderate to very severe COPD who are receiving standard of care therapies

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Keywords

Obstructive Lung Diseases, Chronic Obstructive Pulmonary Disease, Lung Disease, Bronchial Diseases, COPD Exacerbation, Respiratory Tract Diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

1656 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Benralizumab Arm A

Arm Type

Experimental

Arm Description

Benralizumab administered subcutaneously

Arm Title

Benralizumab Arm B

Arm Type

Experimental

Arm Description

Benralizumab administered subcutaneously

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo administered subcutaneously

Intervention Type

Drug

Intervention Name(s)

Benralizumab Arm A

Intervention Description

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Intervention Type

Drug

Intervention Name(s)

Benralizumab Arm B

Intervention Description

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo subcutaneously on study week 0 until study week 48 inclusive

Primary Outcome Measure Information:

Title

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL

Description

Time Frame

From first IP to week 56

Secondary Outcome Measure Information:

Title

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL

Description

Time Frame

From first IP to week 56

Title

Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL

Description

Time Frame

First IP up to end of treatment Week 56

Title

Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL

Description

Time Frame

First IP up to Week 56

Title

Mean Change From Baseline in CAT Total Score for Patients With Baseline EOS>=220/uL

Description

Time Frame

First IP up to Week 56

Title

Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL

Description

Time Frame

First IP up to Week 56

Title

Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL

Description

The number of rescue medication inhalations and nebulizer treatments taken are recorded by the patient in the eDiary twice daily. Total rescue medication use is the sum of daytime and night-time use.

Time Frame

First IP up to Week 56

Title

Mean Change From Baseline in Proportion of Nights Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL

Description

Change from baseline to week 56 in proportion of nights awakenings due to respiratory symptoms.

Time Frame

First IP up to Week 56

Title

Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL

Description

Time Frame