E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe atopic dermatitis (AD). |
|
E.1.1.1 | Medical condition in easily understood language |
Moderate to severe atopic dermatitis (AD). |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
|
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 efficacy of dupilumab over 12 weeks of treatment in adult
patients with moderate-to-severe atopic dermatitis (AD) who have failed or are intolerant to topical steroids with or without topical calcineurin
inhibitors. |
|
E.2.2 | Secondary objectives of the trial |
-Evaluate efficacy over time of dupilumab when administered for up
to 52 weeks.
-Evaluate the long-term safety of dupilumab administered for up to
52 weeks. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional Genomics Sub-study.
- Blood for DNA extraction should be collected on day 1/baseline (predose), but may be collected at any study visit.
- The purpose of the genomic analyses is to identify genomic
associations with clinical or biomarker response to IL-4R/13R
modulation, atopic disease risk, prognosis and progression, or other
clinical outcome measures. |
|
E.3 | Principal inclusion criteria |
1. Male or female, 18 years or older
2. Chronic AD, (according to the American Academy of Dermatology
Consensus Criteria),that has been present for at least 3 years before the
screening visit.
3. Patients with documented recent history (within 6 months before the
screening visit) of inadequate response to a sufficient course of
outpatient treatment with topical AD medication(s), or for whom topical AD therapies are medically inadvisable. |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with dupilumab
2. Recent treatment (within specific time windows before the baseline
visit) with systemic corticosteroids, immunosuppressive agents, topical
corticosteroids and calcineurin inhibitors, live (attenuated) vaccine,
other investigational drugs
3. History of human immunodeficiency virus (HIV) infection
4. HIV or viral hepatitis seropositivity at screening
5. Known or suspected immunosuppresion
6. Recent infections requiring antiinfectious treatment
7. Recent history or high risk of clinical endoparasitoses
8. High risk populations (low life expectancy, severe concomitant
diseases, etc.)
9. Pregnant or breast-feeding women
10. Patients of reproductive potential and sexually active who are
unwilling to use adequate |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of patients with EASI-50 response (reduction of EASI score
by at least 50% from baseline) at week 12.
- Percentage of patients with IGA 0 or 1 at week 12 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- The change from baseline in maximum itch intensity (NRS) at week 12
- The change from baseline in BSA at week 12
- The change from baseline in the erythema of GISS at week 12
- The change from baseline in the infiltration/papulation of GISS at week 12
- The change from baseline in the excoriations of GISS at week 12
- The change from baseline in the lichenification of GISS at week 12
- Percentage of patients achieving EASI-50 response (reduction of EASI
score by at least 50% from baseline) at week 12 and maintaining EASI-50 response on at least 6 of the10 subsequent every 4 weeks (q4w) visits (from visits at weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52); 1 of the 6 must be in the last 4 visits (weeks 40, 44,
48 and 52).
- Percentage of patients with IGA 0 to 1 at week 12 and maintaining IGA 0 to 2 on at least 6 of the10 subsequent q4w visits (from visits at weeks 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52); 1 of the 6 must be in the last 4 visits (weeks 40, 44, 48 and 52).
- The change from baseline in oozing/crusting at week 12
- Incidence of serious treatment-emergent adverse events (TEAEs)
through week 56
- Incidence of study drug discontinuation due to an AE through week 56.
- Incidence of skin-infections through week 56 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 12
2) Week 12.
3) Week 12.
4) Week 12.
5) Week 12.
6) Week 12.
7) Week 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52.
8) Week 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and week 52.
9) Week 12.
10) Week 56
11) Week 56
12) Week 56
|
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
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 | No |
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 |
Belgium |
Bulgaria |
Canada |
Denmark |
France |
Greece |
Italy |
Croatia |
Netherlands |
New Zealand |
Romania |
Australia |
Czech Republic |
Germany |
Hungary |
Korea, Republic of |
Latvia |
Spain |
Poland |
Russian Federation |
Taiwan |
United Kingdom |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |