Study to Evaluate Efficacy and Safety of Benralizumab in Adult Patients with Mild to Moderate Persistent Asthma

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2014-004427-40-DE
• Date of registration: 28/11/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Study to Evaluate Efficacy and Safety of Benralizumab in Adult Patients with Mild to Moderate Persistent Asthma
• Scientific title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients with Mild to Moderate Persistent Asthma
• Date of first enrolment: 19/02/2015
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004427-40
• 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

Countries of recruitment

Canada, Germany, Hungary, Poland, Slovakia, 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 must be obtained prior to any study related procedures being performed and according to international guidelines and/or applicable European Union (EU) guidelines.
2.Female and male aged 18 to 75 years, inclusively, at the time of Visit 1.
3.Women of childbearing potential (WOCBP) must use a highly effective form of birth control (confirmed by the Investigator). Highly effective forms of birth control includes: true sexual abstinence, a vasectomized sexual partner, Implanon® , female sterilization by tubal occlusion, any effective IUD Intrauterine device/IUS Ievonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch ™ or Nuvaring™. WOCBP must agree to use highly effective method of birth control, as defined above, from enrollment, throughout the study duration and until 16 weeks after last dose of investigational product (IP). 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 postemenopausal if they have been amenorrheic for 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific 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.
4.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.
5.Weight of =40 kg.
6.Evidence of asthma as documented by post-bronchodilator (post-BD) reversibility in FEV1 of = 12% demonstrated at Visit 2.
7.Documented use of 1 of the following types of asthma therapy at time of informed consent:
- Low- to medium-dose ICS (ie, 100 to 500 µg fluticasone dry powder formulation equivalents total daily dose) with or without other controller medications, eg, an LTRA and/or theophylline or
- Low-dose ICS/LABA fixed combination therapy (eg, the lowest regular maintenance dose approved in the local country will meet this criterion)
8. Morning pre-bronchodilator (pre-BD) FEV1 of > 50% to = 90% predicted at Visit 2.

Inclusion criteria at randomization
9. At least one of the following symptoms within 7 days prior to randomization:
a. Daytime or nighttime asthma symptom score of =1 for more than or equal to 2 days;
b. Rescue SABA use on at least 2 days; or
c. Nighttime awakenings due to asthma at least 1 night during the 7-day period.
10. For WOCBP: have a negative urine pregnancy test prior to administration of the IP.
11. Demonstrate acceptable inhaler, peak flow meter, and spirometry techniques during screening.
12. Complete symptom scores, PEF measurements and information relating to rescue medication use on 4 or more days out of the last 7 days immediately preceding Visit 3.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
Exclusion criteria:
1.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).
2. 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 studies or their interpretations,
- Impede the patient’s ability to complete the entire duration of study.
3. Known history of allergy or reaction to the investigational product formulation.
4. History of anaphylaxis to any biologic therapy.
5. History of Guillain-Barré syndrome.
6. 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.
7. 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.
8. 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.
9. 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 enroll.
10. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
11.History of cancer:
- 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 patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.

Exclusion criteria at randomization:
12. Absolute FEV1 at randomization visit (Week 0) that changes by more than 20% (negative or positive) from the screening value.
13. An upper respiratory tract infection in the 2 weeks before randomization visit (Week 0).
14. Use of oral corticosteroids during the screening/run-in period.
15. Poorly controlled asthma during the screening/run-in.



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

Health Condition(s) or Problem(s) studied

Asthma
MedDRA version: 18.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

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

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
Other descriptive name: benralizumab
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)

Main Objective: To evaluate the effect of benralizumab on pulmonary function in mild to moderate asthmatic patients

Primary end point(s): Change from baseline in pre-dose forced expiratory volume in 1 second (FEV1)

Secondary Objective: 1. To assess the effect of benralizumab on asthma symptoms and other asthma control metrics;
2. To assess the effect of benralizumab on asthma related and general health-related quality of life;
3. To evaluate the pharmacokinetics, pharmacodynamics, and immunogenicity of benralizumab;

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

Secondary end point(s): - Change from baseline in morning and evening peak expiratory flow (PEF) at home.
- Change from baseline in total asthma symptom score.
- Change from baseline in total asthma rescue medication use (average puffs/day).
- Change from baseline in nighttime awakening due to asthma and requiring rescue medication.
- Change from baseline in mean ACQ-6 score.
- Asthma exacerbations.
- Change from baseline in AQLQ(S)+12 total and domain scores.
- Pharmacokinetic parameters.
- Peripheral blood eosinophil levels.
- Anti-drug antibodies.

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary ID(s)

D3250C00032

2014-004427-40-SK

Source(s) of Monetary Support

AstraZeneca AB