Clinical Trials Register

Summary
EudraCT Number:	2016-002094-36
Sponsor's Protocol Code Number:	D3250C00038
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-09-16
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2016-002094-36

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

SOLANA

A.4.1

Sponsor's protocol code number

D3250C00038

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1185-6625

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Clinical Trial Transparency
B.5.3	Address:
B.5.3.1	Street Address	Vastra Malarehamnen 9
B.5.3.2	Town/ city	Sodertalje
B.5.3.3	Post code	151 85
B.5.3.4	Country	Sweden
B.5.4	Telephone number	46855326000
B.5.5	Fax number	46855329000
B.5.6	E-mail	ClinicalTrialTransparency@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	benralizumab
D.3.2	Product code	MEDI-563
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	benralizumab
D.3.9.1	CAS number	1044511-01-4
D.3.9.2	Current sponsor code	MEDI-563
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	monoclonal antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma

E.1.1.1

Medical condition in easily understood language

Asthma (an illness that causes breathing difficulty) that is not fully controlled, so that episodes of breathing difficulty are still occuring despite the use of other available treatments

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the effect of benralizumab on the time course of change on lung function

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Body plethysmography sub-study. No separate title defined in the main protocol body.

Primary objective: effect of benralizumab on the time course of change in lung function as assessed through body plethysmography. Outcome measure: Residual volume (RV)
Secondary objective: effect of benralizumab on the time course of change in lung function as assessed through body plethysmography. Outcome measures: Total lung capacity (TLC), RV/TLC ratio, Inspiratory capacity (IC), Functional residual capacity (FRC), Vital capacity (VC), Specific airway resistance (SGaw), Airway resistance (Raw)

E.3

Principal 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

E.4

Principal 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 patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained

17. Use of immunosuppressive medication within 3 months prior to the date informed consent

18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥1.5 times the upper limit of normal (ULN) confirmed during screening period.

19. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained

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

21. Receipt of live attenuated vaccines 30 days prior to the date of randomization.

22. Receipt of any investigational medication within 30 days or 5 half-lives prior to randomization, whichever is longer

Exclusion criteria at randomization Visit 4
1. Greater than/equal to 20% change in mean Pre BD FEV1 value (mean of the Pre BD FEV1 taken 30 min (+/- 10 min) and 60 min (+/- 10 min) prior to dosing) at randomization Visit 4 from the mean pre BD FEV1 calculated from the pre BD FEV1 recorded at Visit 2 and Visit 3

E.5 End points

E.5.1

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


E.5.1.1

Timepoint(s) of evaluation of this end point

Day 84 (Visit 10)

E.5.2

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)

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 84 (Visit 10)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Chile

Germany

Hungary

Korea, Republic of

Philippines

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

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:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

230

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-11-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-10-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-08-01

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