A study of the safety and effectiveness of benralizumab to treat patients with severe uncontrolled asthma. - ANDHI

Study identifier:D3250C00045

ClinicalTrials.gov identifier:NCT03170271

EudraCT identifier:2017-001040-35

CTIS identifier:N/A

Study Complete

Official Title

A Multicenter, Randomized, Double-blind, Parallel Group, Placebo controlled, Phase 3b Study to Evaluate the Safety and Efficacy of Benralizumab 30 mg sc in Patients with Severe Asthma Uncontrolled on Standard of Care Treatment

Medical condition

asthma

Phase

Phase 3

Healthy volunteers

Study drug

Benralizumab (Medi-563), Placebo

Sex

All

Actual Enrollment

660

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 07 Jul 2017

Primary Completion Date: 25 Sept 2019

Study Completion Date: 21 Oct 2020

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2021 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Female and male patients aged 18 to 75 years inclusively at the time of Visit 1 with a history of physician-diagnosed asthma requiring treatment with medium-to-high dose Inhaled Corticosteroids (ICS) plus asthma controller, for at least 12 months prior to Visit 1.
2. Documented current treatment with high daily doses of ICS plus at least one other asthma controller for at least 3 months prior to Visit 1.
3. History of at least 2 asthma exacerbations while on ICS plus another asthma controller that required treatment with systemic corticosteroids (IM, IV, or oral) in the 12 months prior to Visit 1.
4. ACQ6 score ≥1.5 at Visit 1.
5. Screening pre-bronchodilator (pre-BD) FEV1 of <80% predicted at Visit 2.
6. Excessive variability in lung function by satisfying ≥ 1 of the following criteria:
a) Airway reversibility (FEV1 ≥12%) using a short-acting bronchodilator demonstrated at Visit 2 or Visit 3.
b) Airway reversibility to short-acting bronchodilator (FEV1 ≥12%) documented during the 12 months prior to enrolment Visit 1.
c) Daily diurnal peak flow variability of >10% when averaged over 7 continuous days during the study run-in period
d) An increase in FEV1 of ≥12% and 200 mL after a therapeutic trial of systemic corticosteroid (eg, OCS), given outside of an asthma exacerbation, documented in the 12 months prior enrolment Visit 1.
e) Airway hyper-responsiveness (methacholine: PC20 of <8 mg/mL, histamine: PD20 of <7.8 μmol, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 months prior to randomization Visit 4.
7. Peripheral blood eosinophil count either:
≥300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2
OR
≥150 to <300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2, IF ≥1 of the following 5 clinical criteria (a to e) is met:
(a) Using maintenance OCS (daily or every other day OCS requirement in order to maintain asthma control; maximum total daily dose 20 mg prednisone or equivalent) at screening
(b) History of nasal polyposis
(c) Age of asthma onset ≥18 years
(d) Three or more documented exacerbations requiring systemic corticosteroid treatment during the 12 months prior to screening
(e) Pre-bronchodilator forced vital capacity <65% of predicted, as assessed at Visit 2 (note that screening pre-BD FEV1 Inclusion Criterion #6 must still be satisfied)
For inclusion in the open label ANDHI IP sub study patients should meet the following criteria:
1.Patients study must have completed ANDHI EOT Visit 11.
2.Written informed consent must also be obtained prior to any study related
procedures being performed in the open label ANDHI IP sub study.
3.Patients who have received any approved or investigational targeted biologic
for the treatment of asthma (e.g. commercial mepolizumab, reslizumab, benralizumab) may be included if the last dose is ≥ 2 months of Visit 13.

Exclusion Criteria

1. Clinically important pulmonary disease other than asthma
2. Acute upper or lower respiratory infections within 30 days prior to the date informed consent.
3. 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.
4. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
5. A history of known immunodeficiency disorder.
6. Current smokers or former smokers with a smoking history of ≥10 pack years.
7. Previously received benralizumab (MEDI-563).
8. Receipt of any investigational medication as part of a research study within approximately 5 half-lives prior to randomization.
9. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
10. Receipt of live attenuated vaccines 30 days prior to the date of randomization; other types of vaccines are allowed.
11. Concurrent enrolment in another interventional or post-authorization safety study
Exclusion criteria for the open label ANDHI IP sub study:
Patients should not enter the open label ANDHI IP sub study if any of the following exclusion criteria
are fulfilled. Each exclusion criterion should be reviewed in all potential participants, including those who transition directly from the double-blind period and those with a delay between completing the EOT Visit 11 and the first
open label visit (Visit 13).
1. Patients who participated in the double-blind period but failed to complete the ANDHI EOT
Visit 11. Patients who completed the ANDHI FU Visit 12 are not excluded from
participation in the ANDHI IP sub study.
2. Unable to commit to the
monthly visits as required by the protocol, or unable to commit to undergoing
protocol guided reductions in asthma therapy, as directed by the Investigator.
3. Patients who experienced
a severe or serious treatment-related AE during the double-blind period and,
and those whom Investigator judges it is not in the patient’s best interest to extend possible treatment with benralizumab.
4. Approved or off-label use of systemic immunosuppressive medications within 3 months prior to the first open label visit (Visit 13). These include but are not limited to small molecules such as methotrexate, cyclosporine, azathioprine, and immunosuppressive/immunomodulating biologics such as tumour necrosis factor (TNF) blockers. Regular use of systemic OCS is also excluded except for the indication of asthma.
5. Receipt of live attenuated vaccines 30 days prior to the first visit in the open label ANDHI IP
sub study (Visit 13); other types of vaccines are allowed.
6. Planned surgical
procedures during the conduct of the study.
7. Positive urine pregnancy test at Visit 13, or currently
breastfeeding or lactating women.

No locations available

Arms	Assigned Interventions
Experimental: Benralizumab (Medi-563) Benralizumab (Medi563) Administered subcutaneously at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) In the open label ANDHI IP sub study, all patients will receive benralizumab subcutaneously at Day 168 (Week 24), Day 196 (Week 28), Day 224 (Week 32), Day 280 (Week 40), Day 336 (Week 48), Day 392 (Week 56), Day 448 (Week 64), and Day 504 (Week 72).	Drug: Benralizumab (Medi-563) 30mg Benralizumab administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) In the open label ANDHI IP sub study, all patients will receive benralizumab subcutaneously at Day 168 (Week 24), Day 196 (Week 28), Day 224 (Week 32), Day 280 (Week 40), Day 336 (Week 48), Day 392 (Week 56), Day 448 (Week 64), and Day 504 (Week 72). Other Name: N/A
Placebo Comparator: Placebo Administered subcutaneously at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days)	Drug: Placebo Placebo administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) Other Name: N/A

Arms

Assigned Interventions

Experimental: Benralizumab (Medi-563)
Benralizumab (Medi563) Administered subcutaneously at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) In the open label ANDHI IP sub study, all patients will receive benralizumab subcutaneously at Day 168 (Week 24), Day 196 (Week 28), Day 224 (Week 32), Day 280 (Week 40), Day 336 (Week 48), Day 392 (Week 56), Day 448 (Week 64), and Day 504 (Week 72).

Drug: Benralizumab (Medi-563)
30mg Benralizumab administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days) In the open label ANDHI IP sub study, all patients will receive benralizumab subcutaneously at Day 168 (Week 24), Day 196 (Week 28), Day 224 (Week 32), Day 280 (Week 40), Day 336 (Week 48), Day 392 (Week 56), Day 448 (Week 64), and Day 504 (Week 72).

Other Name: N/A

Placebo Comparator: Placebo
Administered subcutaneously at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days)

Drug: Placebo
Placebo administered as a subcutaneous injection at Visit 4 (day 0), Visit 6 (day 28 +/- 3 days), Visit 7 (day 56 +/- 3 days) and Visit 9 (day 112 +/- 3 days)

Other Name: N/A

Documents available

CSP redacted
Download
SAP redacted
Download
CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Brad Goodman

Aero Allergy Research Lab of Savannah