問卷
Log In
繁中 EN
TPIDB
TPIDB Outstanding PI
TPIDB > Search Result > Clinical Trials List

Clinical Trials List

Protocol NumberD3251C00004
NCT Number(ClinicalTrials.gov Identfier)NCT02155660

2014-12-01 - 2018-12-31

Phase III

Terminated8

ICD-10J44.9

Chronic obstructive pulmonary disease, unspecified

ICD-9496

Chronic airways obstruction, not elsewhere classified

A randomised, double-blind, double dummy, chronic dosing (56 week) placebo-controlled, parallel group, multicentre, phase III study to evaluate the efficacy and safety of 3 doses of benralizumab (MEDI-563) in patients with moderateto very severe Chronic Obstructive Pulmonary Disease (COPD) with a history of COPD exacerbations (TERRANOVA)

  • Trial Applicant

  • Sponsor

    AstraZeneca

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator KUANG-YAO YANG Division of Thoracic Medicine
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator 鄭世隆 Division of Thoracic Medicine
Far Eastern Memorial Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator 許正園 Division of Thoracic Medicine
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator 何明霖 Division of Thoracic Medicine
CHANGHUA CHRISTIAN HOSPITAL

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator 魏裕峰 Division of Thoracic Medicine
E-DA Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator CHIN-CHOU WANG Division of Thoracic Medicine
Kaoshiung Chang Gung Memorial Hospital of the C.G.M.F.

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator Ping-Hung Kuo Division of Thoracic Medicine
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Condition/Disease

Chronic obstructive pulmonary disease

Objectives

Primary objectives To evaluate the effect of three doses of benralizumab on COPD exacerbations in subjects with moderate to very severe COPD Secondary objectives  To evaluate the effect of three doses of benralizumab on health status/health-related quality of life  To evaluate the effect of three doses of benralizumab on pulmonary function  To evaluate the effect of three doses of benralizumab on respiratory symptoms  To evaluate the effect of three doses of benralizumab on nocturnal awakenings  To evaluate the effect of three doses of benralizumab on rescue medication use  To evaluate the effect of three doses of benralizumab on the severity, frequency and duration of EXACT-PRO defined events.  To evaluate the effect of three doses of benralizumab on other parameters associated with COPD exacerbations  To evaluate the effect of three doses of benralizumab on COPD exacerbations involving emergency room visits and hospitalizations  To evaluate the effect of three doses of benralizumab on health care resource utilization due to COPD  To evaluate the pharmacokinetics and immunogenicity of three doses of benralizumab Safety objectives To evaluate the safety and tolerability of three doses of benralizumab Exploratory objectives  To evaluate the effect of three doses of benralizumab on general health status  To evaluate the impact of three doses of benralizumab on blood eosinophil levels  To evaluate the effect of three doses of benralizumab on blood biomarkers  To understand the dose response relationship across a broad range of doses  To evaluate the effect of three doses of benralizumab on all cause and respiratory related mortality

Test Drug

Benralizumab

Active Ingredient

Benralizumab

Dosage Form

Injection

Dosage

10
100
30

Endpoints

1. Primary efficacy variable:
Annual COPD exacerbation rate, where a COPD exacerbation is defined by symptomatic
worsening of COPD requiring:
 Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of
corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids;
and/or
 Use of antibiotics; and/or
 An inpatient hospitalization due to COPD
2. Secondary efficacy variables:
 St. George’s Respiratory Questionnaire (SGRQ)
 COPD assessment tool (CAT)
 Pre-dose/pre-bronchodilator Forced expiratory volume in one second (FEV1) at the study
centre
 Baseline/Transitional Dyspnea Index (BDI/TDI)
 Exacerbations of Chronic Pulmonary Disease Tool – Respiratory Symptoms (E-RS)
 Number of nights with awakening due to COPD
 Total rescue medication use (average puffs/day)
 Exacerbations of Chronic Pulmonary Disease Tool – Patient-reported Outcome
(EXACT-PRO)
 Time to first COPD exacerbation and proportion of subjects with ≥1 COPD exacerbation
 Annual rate of COPD exacerbations that are associated with an emergency room visit or a
hospitalization
 Annual rate of hospitalizations due to COPD; annual rate of hospitalizations and emergency
department visits combined due to COPD; annual rate of unscheduled outpatient visits
including unscheduled visits to study centres due to COPD; and annual rate of unscheduled
healthcare encounters due to COPD
 PK parameters
 Anti-drug antibodies (ADA)

Inclution Criteria

 Inclusion criteria:
For inclusion in the study subjects should fulfil the following criteria:
1. Provision of informed consent prior to any study specific procedures.
2. Female or male subjects aged 40-85 years inclusive at the time of enrolment (Visit 1).
3. History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC <0.70 and a
post-bronchodilator FEV1 >20% and ≦65% of predicted normal value at screening (central
spirometry will be used for this criteria assessment).
4. Documented history of 2 or more moderate or severe COPD exacerbation that required treatment
with systemic corticosteroids and/or antibiotics, or 1 or more severe COPD exacerbation(s) that
required hospitalization (defined as an inpatient admission ≧24 hour in the hospital, in an
observation area in the emergency department or other equivalent healthcare facility depending
on the country and healthcare system) within 2 to 52 weeks prior to enrolment. Prior use of
antibiotics alone does not qualify as a moderate exacerbation unless specifically used for the
treatment of worsening COPD symptoms.
5. mMRC score ≥1 at Visit 1
6. Subjects should have evidence of having been treated with double (ICS/LABA or
LABA/LAMA) or triple (ICS/LABA/LAMA) therapy approved for COPD in a given country in
the year prior to enrolment (Visit 1). It is acceptable for subjects to have stepped up or stepped
down during that period of time (from double to triple therapy and vice versa), but they have to
consistently treated with current medications and doses at least for 2 weeks prior to enrolment
(Visit 1) Subjects receiving background therapy that is not approved for COPD are not eligible
for the study.
7. Current smoker or ex-smoker with a tobacco history of ≥10 pack-years (1 pack year = 20
cigarettes smoked per day for 1 year).
8. 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 must 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 randomisation without an alternative medical cause. The following
agespecific 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
9. Male subjects who are sexually active must be surgically sterile at least one year prior to Visit 1
or must use an adequate method of contraception (condom with spermicide) from the first dose
of IP until 16 weeks after their last dose. Men with a partner or partners who is (are) not of
childbearing potential are exempt of these requirements.
10. Ability to read, write and use electronic devices.
Additional criteria to be checked prior to randomisation:
11. Blood eosinophils due to a subject’s stratification for blood eosinophil levels. When either
eosinophil stratum (≥300μL or <300μL) is full, subjects in the completed stratum will not be
randomised and will be withdrawn from the study.
12. Compliance with the eDiary defined as completing at least 8 EXACT-PRO/E-RS assessments in
the 14 day period prior to Visit 4 (i.e. Study days -15 to -1).
13. At least 70% compliance with the subject’s maintenance therapy (defined as taking all
maintenance medication as scheduled for the day) during the last 21 days of run-in period (from
Visit 2 to Visit 4) based on the eDiary.

Exclusion Criteria

 Exclusion criteria:
Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
1. Clinically important pulmonary disease other than COPD (e.g. active lung infection, clinically
significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome
associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary
dyskinesia) or ever diagnosed pulmonary or systemic disease, other than COPD, that is
associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary
aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome) and/or radiological
findings suggestive of a respiratory disease other than COPD that is contributing to the subject’s
respiratory symptoms.
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:
- Affect the safety of the subject throughout the study
- Influence the findings of the study or their interpretation
- Impede the subject’s ability to complete the entire duration of study
Subjects who have epilepsy must be on a stable dose of medication for 30 days prior to Visit 4.
3. Unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, renal failure,
uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular
disorder as judged by the Investigator or any ECG abnormality obtained during the
screening/run-in period that in Investigator’s judgement may put the patient at risk or negatively
affect the outcome of the study.
4. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD
exacerbation within 2 weeks prior to enrolment (Visit 1), based on last dose of steroids or last
date of hospitalization whatever occurred later.
5. Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 2
weeks prior to enrolment (Visit 1).
6. Pneumonia within 8 weeks prior to enrolment (Visit 1), based on the last day of antibiotic
treatment or hospitalization date, whatever occurred later.
7. Pregnant, breastfeeding, or lactating women.
8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥1.5 times the upper
limit of normal (ULN) confirmed by repeated testing during screening period.
9. Risk factors for pneumonia (immunosuppression, neurological disorder with increased risk of
aspiration).
10. Known history of allergy or reaction to any component of the investigational product
formulation.
11. History of anaphylaxis to any other biologic therapy.
12. Donation or transfusion of blood, plasma or platelets within the past 90 days prior to Visit 1.
13. Long term oxygen therapy (LTOT) with signs and/or symptoms of cor pulmonale, right
ventricular failure. Subjects receiving long term treatment with oxygen >4.0 liters/minutes
(L/min). While breathing supplemental oxygen, subjects should demonstrate an oxyhemoglobin
saturation ≧89%. In order to be admitted to the trial subjects on LTOT have to be ambulatory
and be able to attend clinic visits.
14. Use of any non-invasive positive pressure ventilation device (NIPPV). Note: Subjects using
continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) for
Sleep Apnea Syndrome are allowed in the study.
15. 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 subject at risk because of his/her participation in the study, or may
influence the results of the study, or the subject’s ability to complete entire duration of the study.
16. Fever >37.8°C (100°F) measured using the tympanic temperature (or equivalent
oral/rectal/axillary temperature) at Visit 4.
17. Use of immunosuppressive medication, including rectal corticosteroids, high potency topical
steroids and systemic steroids within 28 days prior to randomization (Visit 4).
18. Receipt blood products within 30 days prior to enrolment (Visit 1).
19. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit 1.
20. Receipt of any marketed (e.g. omalizumab) or any other monoclonal or polyclonal antibody
therapy taken for any reason within 6 months or 5 half-lives prior to Visit 1, whichever is longer.
21. Receipt of live attenuated vaccines 30 days prior to Visit 4.
22. Seropositive for hepatitis B surface antigen, hepatitis C, or human immunodeficiency virus
(HIV-1 or HIV-2).
23. A helminth parasitic infection diagnosed within 24 weeks prior to Visit 1 that has not been treated
with, or has failed to respond to standard of care therapy.
24. History of alcohol or drug abuse within the past year, which may compromise the study data
interpretation as judged by Investigator or Study Physician.
25. Malignancy, current or within the past 5 years, except adequately treated noninvasive basal cell
and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent
success more than 1 year prior to Visit 1.
26. Subjects who in the opinion of the investigator or qualified designee have evidence of active
tuberculosis (TB), either treated or untreated, or latent TB without completion of an appropriate
course of treatment or appropriate ongoing treatment. Evaluation will be according to the local
standard of care and may consist of history and physical examinations, chest x-ray, and/or TB test
(e.g. purified protein derivative testing etc with the standard of care as determined by local
guidelines).
27. Scheduled in-patient hospitalization or surgical procedure during the course of the study. Elective
hospitalisations that cannot be delayed until after the end of the study need to be discussed with
AstraZeneca Study Physician.
28. Subjects participating in, or scheduled for, an intensive (active) COPD rehabilitation program
(subjects who are in the maintenance phase of a rehabilitation program are eligible to take part).
29. Subjects with lung volume reduction surgery within the 6 months prior to Visit 1. Subjects with
history of partial or total lung resection (single lobe or segmentectomy is acceptable).
30. Employees of the clinical study centre or family members (first-degree relatives) of such
individuals or anyone involved in the planning and/or conduct of the study.
31. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA)
guidelines (GINA 2011) or other accepted guidelines. Subjects with a past medical history of
asthma (e.g. childhood or adolescence) may be included.
32. Treatment with allergy immunotherapy, active or within 90 days prior to Visit 1.
33. Previous treatment with benralizumab (MEDI-563).

The Estimated Number of Participants

  • Taiwan

    36 participants

  • Global

    2168 participants

聯絡我們

台灣臨床試驗主持人資料庫 TPIDB

All Contents Copyright 2020 台灣臨床試驗主持人資料庫TPIDB