A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist

A Multicenter, Open-label, Safety Extension Study With Benralizumab (MEDI-563) for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist (MELTEMI)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02808819

Acronym

MELTEMI

Enrollment

447

Registered

2016-06-22

Start date

2016-06-30

Completion date

2020-06-18

Last updated

2021-04-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases

Brief summary

The purpose of this study is to continue to characterize the safety profile of benralizumab administration and monitor the pharmacodynamic activity of the drug in those asthma patients who remain on treatment for at least 16 weeks and not more than 40 weeks in the predecessor study D3250C00021 (BORA, NCT02258542).

Detailed description

This is an open-label safety extension study designed to evaluate the safety and tolerability of a fixed 30 mg dose of benralizumab administered subcutaneously (SC) in severe asthma patients on inhaled corticosteroid and long-acting β2 agonist (ICS-LABA) therapy with or without chronic oral corticosteroids (OCS) and/or other asthma controllers. All patients will receive active drug on the same dosing regimen they received in BORA (NCT02258542). In order to protect the blind of BORA, patients will remain blinded to treatment regimen allocation until they have completed all end of treatment (EOT) assessments in BORA and signed informed consent for participation in this study, after which treatment allocation will be unblinded to both the investigator and the patient.

Interventions

BIOLOGICALBenralizumab

Benralizumab administered subcutaneously every 4 weeks

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 130 Years

Healthy volunteers

Inclusion criteria

* Informed consent for study participation must be obtained prior to any study related procedures being performed and according to international guidelines and/or applicable European Union guidelines. * Female and male patients who have completed at least 16 and not more than 40 weeks in Study D3250C00021. * Women of childbearing potential (WOCBP) must agree to use an effective form of birth control throughout the study duration and for 16 weeks after the last dose of Investigational Product (IP) * For WOCBP only: Have a negative urine pregnancy test prior to administration of IP at Visit 1. * All male patients who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of IP until 16 weeks after their last dose.

Exclusion criteria

* Any disorder including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric or major physical impairment that is not stable in the opinion of the Investigator and could: * Affect the safety of the patient throughout the study * Influence the findings of the study or their interpretations * Impede the patient's ability to complete the entire duration of study * A helminth parasitic infection diagnosed during a predecessor study that has either required hospitalization, has not been treated, has been incompletely treated or has failed to respond to standard of care therapy * Any clinically significant change in physical examination, vital signs, ECG, hematology, clinical chemistry, or urinalysis during the predecessor study which in the opinion of the investigator may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or interfere with the patient's ability to complete the entire duration of the study * Current malignancy or malignancy that developed during the predecessor study (subjects that had basal cell carcinoma, localized squamous cell carcinoma of the skin which was resected for cure, or in situ carcinoma of the cervix that has been treated/cured will not be excluded). * Receipt of live attenuated vaccines within 30 days prior to initiation of treatment in this study, during the treatment period, and for 16 weeks (5 half-lives) after the last dose of the IP * Receipt of immunoglobulin or blood products within 30 days prior to Visit 1 * Planned major surgical procedures during the conduct of the study * Previous participation in the present study * Concurrent enrolment in another drug-related interventional clinical trial * AstraZeneca staff involved in the planning and/or conduct of the study * Employees of the study center or any other individuals involved with the conduct of the study or immediate family members of such individuals * Patients with important protocol deviations in the predecessor study at the discretion of the Sponsor * Patients with ongoing serious adverse events (SAEs) from the prior study should not be enrolled into the this extension study until the SAE has resolved

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Bilirubin, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in chemistry test Bilirubin.
Change From Baseline in Hematocrit, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Hematocrit.
Change From Baseline in Erythrocytes, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Erythrocytes.
Change From Baseline in Hemoglobin, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Hemoglobin.
Change From Baseline in Alanine Aminotransferase (ALT), Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in chemistry test ALT.
Change From Baseline in Aspartate Aminotransferase (AST), Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in chemistry test AST.
Change From Baseline in Basophils, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Basophils.
Change From Baseline in Leukocytes, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Leukocytes.
Change From Baseline in Lymphocytes, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Lymphocytes.
Change From Baseline in Neutrophils, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Neutrophils.
Change From Baseline in Monocytes, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Monocytes.
Change From Baseline in Platelets, Full Analysis Set	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from baseline in hematologic lab parameter of Platelets.

Secondary

Measure	Time frame	Description
Number of Participants Who Had Health Care Encounter (ie, Hospitalization, Emergency Department Visits, Urgent Care Visits, and All Other Outpatient Visits Due to Asthma) During Study Period	From week 0 to week 184 in study treatment period and through the follow up period (12 weeks from day of last dose). Number and percentage of participants with health care encounters during this period is presented.	Hospitalizations, Emergency department (ED) visits, urgent care visits and all other outpatient visits due to asthma
Change of Blood Eosinophils Count	From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.	Change from Baseline to End of Treatment in blood eosinophils count.
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study	From week 0 to week 184 in study treatment period and plus 12 weeks follow up period	Assessments for the presence of ADA and neutralizing antibody (nAb) throughout study
Duration of Exposure	From week 0 to week 184 in study treatment period	Duration of exposure
Number of Participants With Asthma Exacerbations During Study Period	From week 0 to week 184 in study treatment period and through the follow up period (12 weeks from day of last dose). Number and percentage of participants with asthma exacerbation during this period is presented.	Asthma exacerbation is defined by a worsening of asthma requiring the use of systemic corticosteroids for at least 3 days, and/or an in patient hospitalization, and/or an emergency department or urgent care visit

Countries

Argentina, Australia, Bulgaria, Canada, Chile, Czechia, France, Germany, Poland, Russia, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States

Participant flow

Recruitment details

447 patients enrolled in MELTEMI, 1 patient from Czech Republic was not treated, thus 446 patients received at least 1 dose of IP. Among these treated participants, 347 were from studies SIROCCO(NCT01928771)/CALIMA(NCT01914757) and 99 were from study ZONDA(NCT02075255).

Pre-assignment details

170 participants from SIROCCO(NCT01928771)/CALIMA(NCT01914757) assigned to Benralizumab 30 mg every 4 weeks (q4w) with 1 participant not treated. 178 participants from SIROCCO/CALIMA received Benralizumab every 8 weeks (q8w). 51 participants from ZONDA(NCT02075255) received Benralizumab q4w. 48 participants from study ZONDA received Benralizumab q8w.

Participants by arm

Arm	Count
Benra 30 mg q.4 Weeks Benralizumab administered subcutaneously every 4 weeks	220
Benra 30 mg q.8 Weeks Benralizumab administered subcutaneously every 8 weeks	226
Total	446

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	3	4
Overall Study	Death	1	0
Overall Study	Development of study-specific withdrawal criteria	8	3
Overall Study	eg. no treatment efficacy on asthma	5	4
Overall Study	Lost to Follow-up	1	6
Overall Study	Pregnancy	1	0
Overall Study	Protocol Violation	0	1
Overall Study	Site terminated by sponsor	2	0
Overall Study	Withdrawal by Subject	10	13

Baseline characteristics

Characteristic	Benra 30 mg q.8 Weeks	Total	Benra 30 mg q.4 Weeks
Age, Continuous	53.0 Years STANDARD_DEVIATION 11.64	53.2 Years STANDARD_DEVIATION 11.81	53.5 Years STANDARD_DEVIATION 12
Race/Ethnicity, Customized American Asian	3 Participants	8 Participants	5 Participants
Race/Ethnicity, Customized Black or African	13 Participants	22 Participants	9 Participants
Race/Ethnicity, Customized Other	4 Participants	6 Participants	2 Participants
Race/Ethnicity, Customized White	206 Participants	410 Participants	204 Participants
Sex: Female, Male Female	144 Participants	284 Participants	140 Participants
Sex: Female, Male Male	82 Participants	162 Participants	80 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 220	0 / 226
other Total, other adverse events	169 / 220	145 / 226
serious Total, serious adverse events	44 / 220	47 / 226