|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|Chronic obstructive pulmonary disease and Sputum Eosinophilia
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10010952
|E.1.2||System Organ Class ||10038738 - Respiratory, thoracic and mediastinal disorders
|E.1.3||Condition being studied is a rare disease || No
|E.2 Objective of the trial
|E.2.1||Main objective of the trial ||
|The primary objective of this study is to evaluate the effect of multiple subcutaneous (SC) doses of MEDI-563 on the rate of moderate-to-severe acute axacerbations in COPD (AECOPD) in adult subjects with moderate-to-severe COPD who exhibit eosinophilia (equal to or greater than 3% sputum eosinophilia in the previous 12 months or at screening) compared to placebo
|E.2.2||Secondary objectives of the trial ||
|The secondary objectives of this study are:
1. To evaluate the safety and tolerability of MEDI-563 in this subject population.
2. To evaluate the reduction in hospitalization due to AECOPD.
3. To assess the effect of MEDI-563 on health-related quality of life measurements such as the COPD-specific St. George's Respiratory Questionnnaire (SGRQ-C) and the Chronic Respiratory Questionnaire self-administered standardized format (CRQ-SAS).
4. To describe the effect of MEDI-563 on the BODE (Body Mass Index, Airway Obstruction, Dyspnea, and exercise capacity) index
|E.2.3||Trial contains a sub-study || No
|E.3||Principal inclusion criteria ||
|1. Subjects aged 40 to 85 years old at the time of screening.
2. Written informed consent obtained from the subject prior to
performing any protocol-related procedures.
3. Documented history of moderate to severe COPD with a
post-bronchodilator FEV1/FVC < 0.70 and a
post-bronchodilator FEV1 < 80% predicted at screening.
4. Documented history of 1 or more AECOPD that required treatment
with systemic corticosteroids and/or antibiotics, or hospitalization
within 8 weeks - 52 weeks prior to Day 1.
5. Eosinophilia: greater or same as 3.0% demonstrated on sputum
within 12 months prior to, or at screening.
6. Clinically stable and free from an acute exacerbation of COPD for
8 weeks prior to Day 1.
7. Current smoker or ex-smoker with a tobacco history of more than
or equal to 10 pack-years (1 pack year = 20 cigarettes smoked per
day for 1 year).
8. Female subjects of childbearing potential who are sexually active
with non-sterilized male partner must use adequate contraception
from screening through the end of the study. An acceptable
method of contraception is defined as one that has no higher than
a 1% failure rate. In this study, where medications and devices
containing hormones are included, the recommended methods of
contraception are described in the protocol. Sustained abstinence is
an acceptable practice; however, periodic abstinence, the rhythm
method, and the withdrawal method are not acceptable methods
9. Non-sterilized males who are sexually active with a female of
child-bearing potential must use adequate contraception
(see protocol) from screening through the end of the study.
10. Females not of childbearing potential must have been
surgically sterilized (eg. hysterectomy, bilateral tubal ligation,
or bilateral oophorectomy) or postmenopausal (defined as at
least 1 year since last regular menses) and follicle stimulating
hormone (FSH) > 23 IU/L according to a central
11. Sterilized males must be at least one year post vasectomy or
must use adequate contraception (see Table 4.2.1-1) if less than
one year post vasectomy.
12. Ability and willingness to complete follow-up period as required
by the protocol.
13. Subjects receiving allergy immunotherapy must be on a stable
dose for the preceding 90 days prior to Day 1.
14. Able to read and write.
|E.4||Principal exclusion criteria||
|1. Any condition that, in the opinion of the investigator, would interfere
with evaluation of the investigational product or interpretation of
subject safety or study results.
2. Significant or 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.
3. Pregnant, breastfeeding and lactating women.
4. Known history of allergy or reaction to any component of the
investigational product formulation, budesonide/formoterol
preparations, tiotropium bromide or terbutaline sulphate or
any of their excipients.
5. History of anaphylaxis to any other biologic therapy.
6. Donation or transfusion of blood, plasma or platelets within
the past 90 days prior to screening.
7. Other significant pulmonary disease as a primary diagnosis
(eg, cystic fibrosis, bronchiecstasis, alpha-1 antitrypsin
deficiency, interstitial lung disease; pulmonary hypertension
other than cor pulmonale) if a subject is diagnosed with any
other pulmonary disease as a secondary diagnosis, they may
be included if, in the opinion of the investigator or medical monitor,
the inclusion does not compromise the interpretation of the study.
8. Receiving long-term oxygen therapy (LTOT) at entry into the study.
LTOT is defined as use of oxygen for a minimum of 15 hours per day.
9. Subjects who have a past or present disease or disorder, which is
judged by the investigator and the medical monitor, may either put
the subject at risk because of participation in the study, or may affect
the outcome of the study. Subjects, who have epilepsy, must be on a
stable dose of medication for 30 days prior to Day 1.
10. Influenza vaccination within 3 weeks before sputum collection at
screening (Day -56).
11. Fever > 37.8 °C (100°F) measured using the tympanic temperature
(or equivalent oral/rectal/axillary temperature) at Day 1.
12. Use of immunosuppressive medication, including inhaled (other than
Symbicort®), topical, ocular, nasal or rectal corticosteroids and
systemic steroids within 28 days before randomization (Day 1)
into the study.
13. Receipt of immunoglobulin or blood products within 30 days before
randomization into the study.
14. Receipt of any novel investigational medicinal products within 3
months before the first dose of investigational product in this study
and through to study end.
15. Seropositive for hepatitis B surface antigen, hepatitis C, or human
immunodeficiency virus (HIV)-1 or HIV-2).
16. Unexplained diarrhea within 30 days prior to screening; or a
diagnosis of a helminth parasitic infestation within 6 months prior
to screening; history of an untreated systemic helminth parasitic
infection; history of living with a person known to have had a
helminth parasitic infestation within 12 months prior to screening;
history of recent travel to areas where parasite infestations are
endemic within 3 months before screening.
17. Any subjects that have positive serum serology during the
screening/run-in period to Strongyloides stercoralis will be
excluded. Subjects with a positive serology to Schistosoma mansoni,
Taenia solium, or Ascaris lumbricoides will undergo a confirmatory
stool sampling per local guidelines. If the stool sampling is positive
for Schistosoma mansoni or Taenia solium the subject will be
excluded. All subjects with a positive serology for Ascaris
lumbricoides, whether stool sampling is positive or negative, must
be administered a single oral dose of 400mg albendazole. If
albendazole is not licensed, the subject will be treated per local
standard of care.
18. History of alcohol or drug abuse within the past year that required
treatment that the investigator felt or medical monitor felt would
compromise the study data interpretation.
19. Past or present malignancy within the past 5 years except
adequately treated non-invasive basal cell carcinoma and
squamous cell carcinoma of the skin and cervical carcinoma-in-situ
treated with apparent success more than 1 year prior to screening.
|E.5 End points
|E.5.1||Primary end point(s)||
|The primary objective of this study is to evaluate the effect of multiple SC doses of MEDI-563 on the rate of moderate-to-severe AECOPD in adult subjects with moderate-to-severe COPD. The primary endpoint will be the number of moderate-to-severe AECOPD experienced by subjects after their first dose of investigational product to their Day 393/Early Discontinuation visit.
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| No
|E.7||Trial type and phase
|E.7.1||Human pharmacology (Phase I)|| No
|E.7.1.1||First administration to humans|| No
|E.7.1.2||Bioequivalence study|| No
|E.126.96.36.199||Other trial type description||
|E.7.2||Therapeutic exploratory (Phase II)|| Yes
|E.7.3||Therapeutic confirmatory (Phase III)|| No
|E.7.4||Therapeutic use (Phase IV)|| No
|E.8 Design of the trial
|E.8.1.3||Single blind|| No
|E.8.1.4||Double blind || Yes
|E.8.1.5||Parallel group|| Yes
|E.8.1.6||Cross over || No
|E.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || Yes
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||1
|E.8.5||The trial involves multiple Member States|| Yes
|E.8.5.1||Number of sites anticipated in the EEA||26
|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|| Information not present in EudraCT
|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||
|E.8.7||Trial has a data monitoring committee|| No
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|Date of the last protocol specified visit for the last subject in the study
|E.8.9 Initial estimate of the duration of the trial
|E.8.9.1||In the Member State concerned years||1
|E.8.9.1||In the Member State concerned months||7
|E.8.9.1||In the Member State concerned days||
|E.8.9.2||In all countries concerned by the trial years||1
|E.8.9.2||In all countries concerned by the trial months||7