E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
severe asthma |
schweres Asthma |
|
E.1.1.1 | Medical condition in easily understood language |
severe asthma |
schweres Asthma |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
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 |
- To investigate the effect of vitamin D as add-on therapy to inhaled or oral corticosteroids necessary to control asthma in vitamin D insufficient patients with severe disease |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the effects on rate and time to first and subsequent exacerbations.
- To evaluate the effects on a range of asthma-related clinical and functional Parameters (e.g. ACQ-5 score, AQLQ score, BDI / TDI, FVC, FEV1, RV, TLC, airway resistance, IC, DLCO, serum concentrations of vitamin D, parathormone, calcium, interleukins (IL) 10 and 17, and TNF-alpha |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects meeting all of the following criteria will be considered for enrolment into the trial:
- Male or female, age ≥ 18 years with a pulmonary specialist diagnosis of severe asthma according to the Global Initiative for Asthma (GINA 2014, www.ginasthma.org) and the German Asthma Net (GAN, www. German-asthmanet.de)
- Treatment with long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) at a dose of at least 1000 μg beclomethasone (or equivalent) per day, chronic oral corticosteroid (OCS) use is allowed
- Asthma Control Questionnaire (ACQ-5) score ≥ 1.5
- Vitamin D insufficiency as defined by a serum vitamin D concentration of <30 ng/ml but ≥ 10 ng/ml at screening |
|
E.4 | Principal exclusion criteria |
Subjects presenting one of the following criteria will not be enrolled in the trial:
- Patients on vitamin D substitution
- Impaired renal function (GFR < 30 ml/min) and history of physician-diagnosed nephrolithiasis
- Within the past 4 weeks respiratory tract infection or asthma exacerbation requiring systemic corticosteroids or increase in systemic corticosteroids
- Chronic respiratory diseases (other than asthma)
- Current smokers or ex-smokers with a smoking history of more than 10 packyears |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Relative dose reduction of ICS (μg beclomethasone or equivalent/day) or OCS (mg prednisone or equivalent/day) at the end of study phase II, defined as [initial dose at week 0 – dose at end of phase II (week 24)] / initial dose at week 0. If the dose at end of Phase II has been reduced compared to week 0 and this was followed by an exacerbation within 4 weeks after reduction, the dose before that reduction will be used for the calculation of
relative dose reduction. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Exacerbations (rate of and time to first and subsequent exacerbations)
- ACQ-5 score, AQLQ score, BDI / TDI
- FVC, FEV1, RV, TLC, airway resistance, IC, DLCO
- Serum concentrations of vitamin D, parathormone, calcium, interleukins (IL) 10 and 17, as well as TNF-alpha
- Proportion of patients that achieved vitamin D sufficiency (vitamin D responder: 25-hydroxyvitamin D level ≥ 30 ng/mL)
- Assessment of safety and tolerability by documentation of adverse events (AEs), serious adverse events (SAEs), vital signs, physical examination and laboratory parameters (laboratory test abnormalities/test value changes over time) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 4
week 8
week 12
week 14
week 18
week 20
week 24 |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |