SIROCCO

Overview

Status: Not yet recruiting
Keywords: AstraZeneca , Clinical Trials , Asthma , Benralizumab , SIROCCO
IRB Number: 00069541
Specialty: Pulmonary
Sub Specialties: Asthma

Brief Summary

Primary Objectives

To evaluate the effect of two dosing regimens of benralizumab on asthma exacerbations in patients on high-dose ICS-LABA with uncontrolled asthma.

 

 

Secondary Objectives

  1. To assess the effect of two dosing regimens of benralizumab on pulmonary function
  2. To assess the effect of two dosing regimens of benralizumab on asthma symptoms and other asthma control metrics (as per the ePRO)
  3. To assess the effect of two dosing regimens of benralizumab on other parameters associated with asthma exacerbations
  4. To assess the effect of two dosing regimens of benralizumab on asthma related and general health-related quality of life
  5. To assess the effect of two dosing regimens of benralizumab on emergency room / urgent care visits and hospitalizations due to asthma
  6. To evaluate the effect of two dosing regimens of benralizumab on health care resource utilization and productivity loss due to asthma
  7. To evaluate the pharmacokinetics and immunogenicity of two dosing regimens of benralizumab
  8. To assess the safety and tolerability of two dosing regimens of benralizumab

 

Exploratory Objectives

  1. To assess the impact of two dosing regimens of benralizumab on blood eosinophils levels

 

  1. To evaluate the effect of two dosing regimens of benralizumab on blood biomarkers

 

     3. To collect and store DNA for future exploratory research into genes/genetic variation that may influence response to treatment of asthma (ie, distribution, safety, tolerability and efficacy) and/or predisposition to, or progression of asthma, as well as response or immune response to benralizumab.

Principal Investigator: Gerald Gleich
Department: Dermatology
Co Investigator: Gerald Gleich

Contact Information

Name:Rachel Brodis
Phone: 801-585-9072
Email: rachel.douglas@hsc.utah.edu

Inclusion Criteria

1. Provision of informed consent (and assent if applicable) prior to any study specific procedures

2. Female and male aged from 12 to 75 years, inclusively (at visit 1), patients who are 17 at visit 1 are considered adolescents

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 vasectomised 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 enrolment, throughout the study duration and within 16 weeks after last dose of IP, and 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 would be 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 would be 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.  History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (>250μg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1. Equivalents for fluticasone dry powder can be found in appendix F

7.  Documented treatment with ICS and LABA for at least 3 month prior to Visit 1 with or without oral corticosteriods and additional asthma controllers.  The ICS and LABA can be parts of a combination product or given by separate inhalers.

For subjects 18 years of age and older, the ICS dose must be >500 mcg/day fluticasone propionate dry powder formulation or equivalent daily. For ICS/LABA combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion.

For subjects ages 12-17, the ICS dose must be 500 mcg /day fluticasone propionate dry powder formulation or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion.

If subjects use more than one type of ICS-containing therapy, each should be converted to fluticasone propionate equivalents and summed to derive the subject’s total daily dose. For subjects 18 years of age, if that sum is >500 mcg of fluticasone propionate equivalents dry powder formulation daily, the subject is eligible for the study. For subjects 12-17 years of age, if that sum is 500 mcg of fluticasone propionate equivalents dry powder formulation daily, the subject is eligible for the study.

8.  Additional maintenance asthma controller medications (eg LTRAs, tiotropium, cromone, theophylline and oral corticosteroid), that have been stable for at least 30 days prior to Visit 1, are allowed.  

9.  Pre-bronchodilator (Pre-BD) FEV1 of <80% predicted (<90% predicted for patients12 to 17 years old) at Visit 2 (week -3)

10. At least 2 documented asthma exacerbations in the 12 months prior to the date informed consent (assent) is obtained that required use of a systemic corticosteroid or a temporary increase from the subject’s usual maintenance dose of oral corticosteroid (please refer to section 4.1.1)

11. ACQ-6 score ≥ 1.5 at Visit 1  

12. Documented post-bronchodilator (post-BD) reversibility in FEV1 of >12% and >200 mL in FEV1 within 12 months prior to visit 1.  If historical documentation is not available, reversibility must be demonstrated and documented at Visit 2. 

Inclusion criteria at randomization

13. For WOCBP only: have a negative urine pregnancy test prior to administration of the IP at Visit 4.

14. Fulfilment of at least one of the following conditions over the 7 days prior to randomization:

  • > 2 days with a daytime or night time symptoms score >
  • Rescue SABA use on > 2 days 
  • ≥1 nocturnal awakening due to asthma

15. Pre-BD FEV1 of <80% (<90% predicted for patients 12 to 17 years old) predicted at day of randomization visit

16. Patients demonstrate acceptable inhaler, peak flow meter, and spirometry techniques during run-in (from Visit 2 to Visit 4)

17. At least 70% compliance with usual asthma controller ICS-LABA during run-in period (from Visit 2 to Visit 4) based on Asthma Daily Diary.  (Patients who experience an asthma exacerbation during run-in may temporarily be unable to complete their diary due to illness or hospitalization. In these cases, ICS-LABA compliance will be calculated for the period after systemic corticosteroid therapy is complete.

18.  Minimum 80% compliance with ePRO completion

  • 80% compliance defined as completing Asthma Daily Diary for any 8 mornings and any 8 evenings of the last 10 days of the run-in period

    Inclusion criteria for optional pharmacogenetic research

  • 19. Provision of informed consent for pharmacogenetic sampling and analysis

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.  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:

  1. Affect the safety of the patient throughout the study 
  2. Influence the findings of the studies or their interpretations 
  3. 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.  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

6.  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

7.  Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in 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

8.  Any clinically significant cardiac disease or any 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

9.  History of alcohol or drug abuse within 12 months prior to the date informed consent (and assent if applicable) is obtained

10. 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

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

12. Current smokers or former smokers with a smoking history of > 10 pack-years

13. 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 (assent if applicable) 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 (assent if applicable) was obtained

14. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained. Chronic maintenance prednisone for the treatment of asthma is allowed

15. Receipt of immunoglobulin or blood products within 15 days prior to the date informed consent (and assent if applicable) is obtained

16. Receipt of any marketed (eg omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent (assent if applicable) is obtained, whichever is longer

17. Receipt of live attenuated vaccines 30 days prior to the date of randomization (exception for adolescents in the EU - see protocol)

  • Receipt of inactive/killed vaccinations (e.g. inactive influenza) are allowed provided they are not administered within 1 week before/after any study visit

18.  Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer

19.  Previously randomized in any benralizumab (MEDI-563) study.

20. Initiation of new allergen immunotherapy within 30 days prior to the date of informed consent (assent if appliacble).  Immunotherapy initiated prior to this period or as a routine part of the patient’s seasonal treatment is allowed. If the immunotherapy is delivered as an injection, there should be a gap of 7 days between the immunotherapy and IP administration.

21. Current use of any oral or ophthalmic non-selective β-adrenergic antagonist (e.g., propranolol)

22. Planned surgical procedures during the conduct of the study

23. Currently breastfeeding or lactating women

24. Previous randomization in the present study

25. Concurrent enrolment in another clinical trial

26. AstraZeneca staff involved in the planning and/or conduct of the study

27. Employees of the study centre or any other individuals involved with the conduct of the study, or immediate family members of such individuals

28. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level 2.5 times the upper limit of normal (ULN) confirmed during screening period.

29. Five-lipoxygenase inhibitors (eg, Zileuton) and roflumilast are prohibited.

Exclusion criteria for optional pharmacogenetic research

30. Previous allogeneic bone marrow transplant

31. Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection