A Study to Evaluate the Onset of Effect and Time Course of Change in Lung Function With Benralizumab in Severe, Uncontrolled Asthma Patients With Eosinophilic Inflammation

NCT02869438 | Completed Phase 3 Results

• 3 other identifiers: D3250C000382016-002094-36U1111-1185-6625
• Study Type: interventional
• Target: 233
• Locations: 6 countries
• Sites: 54

Brief Summary

The purpose of this study is to investigate the onset and maintenance of effect of benralizumab on lung function, blood eosinophils, asthma control metrics and quality of life during 12-week treatment in patients with uncontrolled, severe asthma with eosinophilic inflammation. A subset of patients will take part in body plethysmography substudy to further investigate the effect on lung function.

Conditions

Asthma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Change From Baseline (Visit 4) to Day 28 (Visit 8), Day 56 (Visit 9), and Day 84 (Visit 10) in Pre-BD FEV1

  The average over the mean differences between benralizumab and placebo for change from baseline in pre-BD FEV1 is used to determine if the study is positive and to determine maintenance of effect. The first post baseline time point where the p-value for the mean difference between benralizumab and placebo is less than or equal to 0.05 is used to determine time to onset of effect.

  From first IP dose to Day 84

• Change From Baseline (Visit 4) to End of Treatment Day 84 (Visit 10) in Residual Volume (RV)

  Body plethysmography was performed for sub-study patients. Lung volume subdivisions measures were performed by the investigator or qualified designee according to ATS/ERS guidelines.

  From first IP dose to Day 84

Secondary Outcomes (13)

• Percent Change From Baseline to End of Treatment in Eosinophils Counts

  From first IP dose to Day 84

• Change From Baseline (Visit 4) to Post Baseline Visits in Pre-BD FEV1

  From first IP dose to Day 84

• Change From Baseline to Post Baseline for Pre-BD FVC

  From first IP dose to Day 84

• Percentage of Pre-BD FEV1 Responder

  From first IP dose to Day 84

• Change From Baseline in ACQ-6

  From first IP dose to Day 84

Other Outcomes (8)

• Serum Concentration of Benralizumab

  From first dose to end of treatment period (Day 84)

• PK Parameter of Benralizumab (Cmax)

  First IP dose cycle (ie, data collected on Days 3, 7, 14 and 28)

• Anti-drug Antibody Responses

  From first IP dose to end of treatment period (Day 84)

Study Arms (2)

Benralizumab arm

EXPERIMENTAL

Benralizumab administered subcutaneously

Drug: Benralizumab

Placebo arm

PLACEBO COMPARATOR

Placebo administered subcutaneously

Other: Placebo

Interventions

Benralizumab DRUG

Benralizumab administered subcutaneously at Visit 1 (Day 0), Visit 8 (Day28 +/- 3 days) and Visit 9 (Day 56 +/- 3 days)

Benralizumab arm

Placebo OTHER

Placebo administered subcutaneously at Visit 1 (Day 0), Visit 8 (Day28 +/- 3 days) and Visit 9 (Day 56 +/- 3 days)

Placebo arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written 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 (EU) guidelines.
• Female and male aged 18 to 75 years inclusively at the time of Visit 1
• Documented current treatment with ICS and LABA for at least 30 days prior to Visit 1. The ICS and LABA can be parts of a combination product or given by separate inhalers. The ICS dose must be greater than or equal to 500 μg/day fluticasone propionate dry powder formulation or equivalent daily. Additional asthma controller medications, eg, oral corticosteroids, long-acting antimuscarinics (LAMAs), LTRAs, theophylline etc. are allowed if they have been used for at least 30 days prior to Visit 1
• History of at least 2 asthma exacerbations that required treatment with systemic corticosteroids (intramuscular (IM), intravenous (IV), or oral) in the 12 months prior to Visit 1. For patients receiving corticosteroids as a maintenance therapy, the corticosteroid treatment for the exacerbation is defined as a temporary increase of their maintenance dose.
• Pre-bronchodilator (pre-BD) FEV1 of \< 80% predicted at Visit 2 or Visit 3
• ACQ-6 score ≥1.5 at Visit 1
• Evidence of asthma as documented by airway reversibility (FEV1 ≥12% and 200 ml) demonstrated at Visit 1, Visit 2 or Visit 3. For patients entering the body plethysmography sub-study, reversibility must be demonstrated at Visit 1 or at Visit 2 only
• Peripheral blood eosinophil count of ≥300 cells/μL assessed by central lab at Visit 1
• Women of childbearing potential (WOCBP) must use an effective form of birth control confirmed by the Investigator. WOCBP must also have negative serum pregnancy test result on Visit 1.
• Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of randomization without an alternative medical cause. The following agespecific requirements apply:
• Women \<50 years old are considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Women ≥50 years old are considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
• 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
• Weight of ≥40 kg
• At least 1 of the following within 7 days prior to randomization:

You may not qualify if:

• Clinically important pulmonary disease other than asthma (eg, active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome)
• Life-threatening asthma defined as episodes requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episodes within the 12 months prior to Visit 1.
• Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
• An upper respiratory tract infection or an asthma exacerbation that required treatment with systemic corticosteroids or an increase in regular maintenance dose of OCS during the screening/run-in period prior to randomization Visit 4
• Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, 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 studies or their interpretations
• Impede the patient's ability to complete the entire duration of study
• Known history of allergy or reaction to any component of the investigational product formulation
• History of anaphylaxis to any biologic therapy
• History of Guillain-Barré syndrome
• A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy
• Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening period, 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 the patient's ability to complete entire duration of the study
• Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which in the opinion of the Investigator may put the patient at risk or interfere with study assessments
• History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (54)

Research Site

Scottsboro, Alabama, 35768, United States

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Gilbert, Arizona, 85234, United States

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Denver, Colorado, 80206, United States

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Miami, Florida, 33174, United States

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Tampa, Florida, 33607, United States

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Vero Beach, Florida, 32960, United States

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Winter Park, Florida, 32789, United States

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Fort Mitchell, Kentucky, 41017, United States

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Rochester, Minnesota, 55905, United States

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New Bern, North Carolina, 28562, United States

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Cincinnati, Ohio, 45231, United States

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Oklahoma City, Oklahoma, 73103, United States

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Medford, Oregon, 97504, United States

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Philadelphia, Pennsylvania, 19140, United States

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Lampasas, Texas, 76550, United States

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McKinney, Texas, 75069, United States

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Curicó, 3341643, Chile

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Santiago, 404366, Chile

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Santiago, 7500692, Chile

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Santiago, 7750495, Chile

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Bamberg, 96049, Germany

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Darmstadt, 64283, Germany

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Frankfurt, 60596, Germany

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Frankfurt am Main, 60389, Germany

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Frankfurt am Main, 60596, Germany

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Hamburg, 20354, Germany

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Hamburg, 22299, Germany

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Hanover, 30167, Germany

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Hanover, 30625, Germany

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Hanover, D-30173, Germany

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Mainz, 55131, Germany

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München, 81377, Germany

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Balassagyarmat, 2660, Hungary

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Edelény, 3780, Hungary

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Farkasgyepü, 8582, Hungary

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Gödöllő, 2100, Hungary

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Hajdúnánás, 4080, Hungary

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Komárom, 2900, Hungary

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Miskolc, 3529, Hungary

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Pécs, 7626, Hungary

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Pécs, 7635, Hungary

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Iloilo City, 5000, Philippines

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Lipa City, Philippines

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Manila, 1000, Philippines

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Quezon City, 0870, Philippines

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Cheongju-si, 28644, South Korea

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Daegu, 42415, South Korea

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Jeonju, 54907, South Korea

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Seoul, 03080, South Korea

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Seoul, 03312, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

Location

Related Links

• Protocol
• SAP

MeSH Terms

Conditions

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

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Ubaldo Martin, Global Clinical Lead Benralizumab
• Organization: AstraZeneca

Ubaldo.Martin@astrazeneca.com

+1 301 398 0163

Study Officials

• Reynold A Panettieri, Doctor of Medicine

  Child Health Institute of NJ, 89 French Street, Suite 4210, New Brunswick, NJ, 08901, USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2016
• First Posted: August 17, 2016
• Study Start: November 9, 2016
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: October 29, 2019
• Results First Posted: October 7, 2019

Record last verified: 2019-10

Locations

DE (12); KR (9); PH (4); HU (9); US (16); CL (4)