E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 |
Assess the safety of SCH 527123 in subjects with neutrophilic asthma |
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E.2.2 | Secondary objectives of the trial |
Effect of treatment with SCH 527123 on sputum neutrophils, asthma symptoms, pulmonary function tests, quality of life, electrocardiograms, laboratory assessments and adverse events. PK of SCH 527123. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must be 18 to ≥70 years of age, of either sex, and any race.
2. Subject must have an induced sputum neutrophil count ≥40% of total WBCs and <10 million/mL at Screening (Visit 1 assessment).
3. Subject must have a documented diagnosis of asthma (within the past 5 years), which will be determined by at least one of the following: ≥12% and 200 mL improvement in FEV1 post-bronchodilator, and/or airway hyperresponsiveness (eg, positive methacholine challenge <8 mg/mL).
4. Subject must be a nonsmoker or previous smoker with a cumulative smoking history of less than 20 pack years (pack-year = 20 cigarettes smoked daily for 1 year). Previous smokers may not have smoked within 1 year prior to Screening.
5. Subject must not have had an exacerbation of asthma for the 4 weeks prior to Screening and subject must be on a stable medication regimen for asthma for at least 4 weeks prior to Screening.
6. Subject must be receiving ≥800 mcg/day of beclomethasone dipropionate (BDP) or equivalent for at least 3 months prior to Screening (and on a stable dose for at least 4 weeks prior to Screening). Equivalent doses of ICS are defined as follows:
DRUG MEDIUM DAILY DOSE (mcg) HIGH DAILY DOSE (mcg) Beclomethasone-CFC 500-1000 >1000 Beclomethasone-HFA 250-500 >500 Budesonide-DPI 600-1000 >1000 Budesonide-Neb Inhalation Suspension 1000-2000 >2000 Flunisolide 1000-2000 >2000 Fluticasone 250-500 >500 Mometasone Furoate 400-800 >800 Triamcinolone acetonide 1000-2000 >2000
7. Subject must be willing to give written informed consent to participate in the study.
8. Subject must be capable of complying with the dosing regimen, adhere to the visit schedule, and participate in all treatment procedures, including sputum induction.
9. 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 and Treatment Periods). Medically acceptable, highly effective forms of birth control are hormonal implants, oral contraceptives, medically acceptable prescribed intrauterine devices (IUDs), and monogamous relationship with a male partner who has had a vasectomy. 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.
10. A 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 women who use a highly effective birth control method.
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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).
2. Subject who has an upper or lower respiratory tract infection at Screening or has had one within 4 weeks prior to Screening.
3. Subject who has received any of the following treatments more recently than the indicated washout period prior to Screening.
Prohibited Medications Approximate Washout Period Prior to Screening Omalizumab 5 months Methotrexate, cyclosporine, gold, & other cytotoxic drugs 3 months Investigational drugs 30 days 5-Lipooxygenase (5-LO) inhibitors (eg, Zileuton) 2 weeks Antibiotics 4 weeks Antiviral drugs 4 weeks
4. Subject who produced an inadequate amount of sputum for evaluation at the Screening Visit (Visit 1) or is known to have difficulty producing sputum.
5. Subjects with a total sputum neutrophil count of over 10 million/mL at the Screening Visit.
6. Subjects with a PBN count of <3000/µL at the Screening Visit (Visit 1).
7. Subject with a post-bronchodilator FEV1 <1L.
8. Subjects with clinically significant chronic infectious disease(s) (eg, HIV, hepatitis B or C).
9. Subject with allergy/sensitivity to the study drug or its excipients.
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 of Screening.
12. Subject with other clinically relevant medical condition(s) (eg, hematologic, cardiovascular, renal, hepatic, neurologic, or metabolic) or who is using medication that may interfere with the effect of the study medication.
13. Subject who has used any investigational drug within 30 days of Screening.
14. Subject who is participating in any other clinical study.
15. Subject who is part of the staff personnel directly involved with this study.
16. Subject who is a family member of the investigational study staff.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety as defined by the proportion of subjects in each treatment group who maintain a peripheral blood neutrophil count ≥1500/µL during the 4-week treatment period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | 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
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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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |