| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
|
| 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 assess the effect of SCH 527123 on severe asthma exacerbations in subjects with severe asthma. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objectives of this study are to assess the safety and tolerability of SCH 527123 in subjects with severe asthma. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Subject must have severe asthma, as defined by the following Inclusion/Exclusion criteria, be at least 18 to ≤70 years of age, of either sex, and any race. 2. Subject must demonstrate a ≥12% and ≥200 mL improvement in post-bronchodilator FEV1 at Screening or have a history of FEV1 reversibility or a positive methacholine challenge <8 mg/mL within the 5 years prior to Screening. If the subject does not have a history of FEV1 reversibility or a positive methacholine challenge, and the subject fails the reversibility test at Screening, the reversibility test may be repeated up to two additional times. 3. Subject must have had at least two severe asthma exacerbations in the year prior to Screening (defined as asthma exacerbations requiring an addition or an increase in systemic corticosteroids, or hospitalization, or emergency room [ER] visit for asthma). Subject-reported history of asthma exacerbations obtained by the investigator will be considered acceptable. 4. Subject must be receiving ≥1000 µg/day of beclomethasone dipropionate(BDP) or equivalent for at least 3 months prior to Screening (and have been on a stable dose for at least 6 weeks prior to Screening). 5. Subject must be a nonsmoker or previous smoker with a cumulative smoking history of ≤20 pack-years (pack-year = 20 cigarettes smoked daily for 1 year). Previous smokers may not have smoked within 1 year prior to Screening. 6. Subject must be on a stable asthma regimen for at least 6 weeks prior to Screening and agree to remain on this stable asthma regimen throughout the study. 7. Pre-bronchodilator FEV1 must be ≥40% to ≤90% of predicted FEV1 at Screening. 8. Subject must be willing to give written informed consent to participate in the study. 9. Subject must be capable of complying with the dosing regimen, adhere to the visit schedule, and participate in all treatment procedures, including sputum induction (at applicable study centers). 10. A female subject of childbearing potential must have a negative serum pregnancy test (hCG) at Screening and must be using a medically acceptable, highly effective, adequate form of birth control (ie, failure rate <1% per year when used consistently and correctly) prior to Screening and agree to continue using it while in the study (Screening, treatment, and follow-up periods) if she is heterosexually active. Medically acceptable, highly effective forms of birth control are hormonal implants and patches, oral contraceptives, medically acceptable prescribed intrauterine devices (IUDs), and monogamous relationship with a male partner who has had a vasectomy. A female subject who is not of childbearing potential must have a medical record of being surgically sterile (eg, hysterectomy, tubal ligation), or be at least 1 year postmenopausal. Absence of menses for at least 1 year will indicate that a female is postmenopausal. A female subject should be encouraged to continue using a highly effective method of birth control for 30 days following the end of treatment. 11. A female subject of childbearing potential who is not currently sexually active must agree to use a highly effective method of contraception should she become heterosexually active while participating in the study. 12. A heterosexually active male subject must agree to use an adequate form of contraception for the duration of the study and agree to have sexual relations only with those women using a highly effective birth control method. A highly effective method of birth control is defined as that which results in a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as hormonal implants and patches, oral contraceptives, and medically acceptable prescribed IUDs. |
|
| E.4 | Principal exclusion criteria |
| 1. Subject who has been diagnosed with COPD or any other clinically relevant lung disease, other than asthma (eg, cystic fibrosis, pulmonary fibrosis, bronchiectasis) that, in the opinion of the investigator, precludes the subject from participating in the study. 2. Subject who has had an upper or lower respiratory tract infection within 6 weeks prior to Screening. Subject with acute, non-respiratory infection(s) at Screening should be excluded until resolution of the infection(s), as determined by the investigator. (The investigator should carefully look for signs and symptoms of any infections by taking a detailed history and physical examination.) 3. Subject requiring a change in asthma medication prior to randomization. 4. Subject who has received any treatment listed in Table 4 of the protocol more recently than the indicated washout period prior to Screening. 5. Subject who fails to enter at least 7 complete days of diary data into the electronic diary (eDiary) during the Screening Period. 6. Subject with allergy/sensitivity to the study drug or its excipients. 7. Subject with a PBN count <3.0 x 10^9/L at Screening. Note: if a subject's PBN count is <3.0 x 10^9/L at the Screening Visit, at the investigator's discretion, the PBN count may be repeated up to 2 additional times. 8. Subject who had an asthma exacerbation, as determined by the investigator, within 6 weeks prior to or during the Screening Period. 9. Subject with a post-bronchodilator FEV1<1L before sputum induction (only at centers participating in sputum induction). 10. Woman who is breast-feeding, pregnant, or intends to become pregnant during the study. 11. Subject requiring mechanical ventilation for a respiratory event within 6 months prior to Screening. 12. A subject, who, in the opinion of the investigator, has relevant medical conditions (eg, hematologic, cardiovascular, renal, hepatic, neurologic, metabolic, or rheumatologic) or who is using medication that may interfere with the effect of the study medication. 13. Subject with clinically significant infectious diseases (eg, human immunodeficiency virus [HIV], hepatitis B or C). 14. Subject who has used any investigational drug within 30 days (or 5 halflives, whichever is greater) of Screening. 15. Subject who is participating in any other clinical study (excluding observational studies). 16. Subject who is part of the staff personnel directly involved with this study. 17. Subject who is a family member of the staff personnel directly involved with this study. 18. Subject who is has a reversed awake/asleep schedule (eg, night shift worker). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the time to first severe asthma exacerbation and will be analyzed using the log-rank test; 95% confidence intervals and p-values will be provided for pairwise comparison. |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 63 |
| 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 | Yes |
| 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
|
|
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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