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

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2016-002094-36-HU
• Date of registration: 16/09/2016
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: 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
• Scientific title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3b 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 - SOLANA
• Date of first enrolment: 22/11/2016
• Target sample size: 230
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002094-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Chile, Germany, Hungary, Korea, Republic of, Philippines, United States

Contacts

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent for study participation obtained prior to any study related procedures being performed and according to international guidelines

2. Female and male patients aged 18 to 75 years, inclusively at Visit 1.

3. Documented history of current treatment with ICS and LABA for at least 30 days before Visit 1

4. History of at least 2 asthma exacerbation that required treatment with systemic corticosteroids in the 12 months prior to Visit 1.

5. Pre-bronchodilator (pre-BD) FEV1 of < 80% predicted at Visit 2 or Visit 3

6. ACQ-6 score= 1.5 at Visit 1

7. Evidence of asthma as documented by airway reversibility (FEV1 =12% and 200 ml) demonstrated at Visit 1, Visit 2 or Visit 3. For patients in the body plethysmography substudy, reversibility to be demonstrated at Visit 1 or at Visit 2 only

8. Peripheral blood eosinophil count of =300 cells/µL assessed by central lab at Visit 1

9. Women of childbearing potential (WOCBP) must use an effective form of birth control

10. All sexually active male patients must agree to use a double barrier method of contraception from the first dose of IP until 16 weeks after their last dose

11. Weight of =40 kg

Inclusion criteria at randomization Visit 4:
1. At least one of the following within 7 days prior to randomization:
- Daytime or nighttime asthma symptom for 2 or more days;
- Rescue SABA use on at least 2 days
- Nighttime awakenings due to asthma at least 1 night during the 7-day period
2. ACQ >0.75 at Visit 4 prior to randomisation
3. A negative urine pregnancy test in WOCBP prior to administration of IP

Additional inclusion criteria applicable for the Body Plethysmography substudy:
1. Residual volume =125% of predicted at Visit 3




Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1. Clinically important pulmonary disease other than asthma (e.g. 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 (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome)

2. Life-threatening asthma within the 12 months prior to Visit 1

3. 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

4. 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 randomisation Visit 4

5. 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 or impede the patient’s ability to complete the entire duration of study

6. Known history of allergy or reaction to any component of the investigational product formulation

7. History of anaphylaxis to any biologic therapy

8. History of Guillain-Barré syndrome

9. 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

10. 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

11. 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

12. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained

13. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol

14. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test

15. Current smokers or former smokers with a smoking history of =10 pack years

16. Current malignancy, or history of malignancy, except for:
- Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
- Patients who have had other malignancies are eligible provided that the patien

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Asthma
MedDRA version: 19.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: benralizumab
Product Code: MEDI-563
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: benralizumab
CAS Number: 1044511-01-4
Current Sponsor code: MEDI-563
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Change from baseline to end of treatment between benralizumab and placebo in pre-BD FEV1.

Body plethysmograpfy sub-group primary endpoint:
1. Change from baseline to end of treatment in Residual volume (RV) compared to placebo
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Main Objective: To determine the effect of benralizumab on the time course of change on lung function

Timepoint(s) of evaluation of this end point: Day 84 (Visit 10)

Secondary Objective: 1.To determine time course of effect of benralizumab on blood eosinophils and correlate changes in eosinophil depletion with lung function
2. To determine the effect of benralizumab on the time course of change and maintenance on lung function
3. To determine the time course of the effect of benralizumab on asthma control metrics
4. To determine the time course of effect of benralizumab on health related quality of life
5. To determine the effect of benralizumab on the time course of change in exhaled nitric oxide (FeNO)
6. To evaluate the pharmacokinetics and immunogenicity of benralizumab
7. To assess the safety and tolerability of benralizumab
8. To evaluate patient impression of overall asthma severity and overall change from baseline as reported by the patient and clinician

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 84 (Visit 10)

Secondary end point(s): 1. Change from baseline in blood eosinophils (from hematology) to end of treatment
2. Change from baseline in pre-BD FEV1 at all clinic visits compared to placebo
3. Change from baseline in pre-BD forced vital capacity (FVC) at all clinic visits compared to placebo
4. Change from baseline in ACQ-6 score at all post-baseline assessment timepoints
5. Change from baseline in SGRQ score at all postbaseline assessment timepoints
6. FeNO (ppb)
7. Serum PK and anti-drug antibodies
8. AEs, SAEs, laboratory variables, physical examination
9. CGIC, PGI-S and PGIC assessments

Body plethysmograpfy sub-group secondary endpoints:
1. Change from baseline to end of treatment in the following measures compared to placebo :
-Total lung capacity (TLC)
-RV/TLC ratio
-Inspiratory capacity (IC)
-Functional residual capacity (FRC)
-Vital capacity (VC)

Secondary ID(s)

D3250C00038

Source(s) of Monetary Support

AstraZeneca AB