E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease and Sputum Eosinophilia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 |
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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 |
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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.
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 of contraception.
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 laboratory.
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 vascectomy.
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. |
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E.4 | Principal exclusion criteria |
1. Any condition that 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 Investigator or any other relevant cardiovascular disorder as judged by Investigator 3. Pregnant, breastfeeding or lactating women 4. Known history of allergy/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 past 90 Days prior to screening 7. Other significant pulmonary disease as a primary diagnosis if a subject is diagnosed with any other pulmonary diseases as a secondary diagnosis they may be included if, in the opinion of the investigator/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 min. of 15 hrs per day 9. Subjects who have 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 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 wks before sputum collection at screening (Day -56) 11. Fever >37.8 °C (>100°F) measured using the tympanic temperature (or equiv. oral/rectal/axillary temperature) at Day 1 12. Use of immunosuppressive medication, including inhaled (other than Symbicort®), topical, ocular, nasal or rectal corticosteroids & 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 diagnosis of helminth parasitic infestation within 6 months prior to screening; history of untreated systemic helminth parasitic infection; history of living with 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 screening/run-in period to Strongyloides stercoralis will be excluded. Subjects with positive serology to Schistosoma mansoni, Taenia solium, or Ascaris lumbricoides will undergo a confirmatory stool sampling per local guidelines1. If 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 20. 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 prophylactic 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 (eg, purified protein derivative testing, etc with the standard of care as determined by local guidelines) 21. Scheduled in-patient hospitalization during the course of study 22. Subjects participating in, or scheduled for, an intensive COPD rehabilitation program (subjects who are in maintenance phase of a rehabilitation program are eligible to take part) 23. Subjects with lung volume reduction surgery within 12 months prior to screening 24. Employees of clinical study site/family members (first-degree relatives) of such individuals 25. Current diagnosis of asthma according to Global Initiative for Asthma (GINA) guidelines (GINA-2009) 26. Previous treatment with MEDI-563
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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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | 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.7.1.3 | Other | No |
E.7.1.3.1 | 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 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
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.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
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Date of the last protocol specified visit for the last subject in the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |