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 | 17.1 |
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 |
The primary objective of the study is to demonstrate the efficacy of dupilumab administered concomitantly with TCS through week 16 in adult patients with moderate-to-severe AD. |
|
E.2.2 | Secondary objectives of the trial |
- Evaluate long-term efficacy of dupilumab when administered concomitantly with TCS for up to 52 weeks.
- Evaluate the long-term safety of dupilumab when administered concomitantly with TCS 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). |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with dupilumab
2. Important side effects of topical medication (eg, intolerance to treatment, hypersensitivity reactions, significant skin atrophy, systemic effects), as assessed by the investigator or patient's treating physician.
3. At baseline visit >= 30% of the total lesional surface located on areas of thin skin that cannot be safely treated with medium or higher potency TCS (eg, face, neck, intertriginous areas, genital areas, areas of skin atrophy).
4. 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
5. History of human immunodeficiency virus (HIV) infection
6. HIV or viral hepatitis positive serology at screening
7. Known or suspected immunosuppresion
8. Recent infections requiring antiinfectious treatment
9. Recent history or high risk of clinical endoparasitoses , unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization
10. High risk populations (low life expectancy, severe concomitant diseases, etc.)
11. Pregnant or breast-feeding women
12. Patients of reproductive potential and sexually active who are unwilling to use adequate |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Proportion of patients with EASI-75 response (reduction of EASI score by >=75% from baseline) at week 16
- Proportion of patients with both an IGA 0 or 1 (on a 5-point scale) and a reduction from baseline of >=2 points at week 16 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Percent change from baseline to week 16 in Pruritus NRS
- Proportion of patients with improvement (reduction) of Pruritus NRS >=3 from baseline to week 16
- Proportion of patients with an IGA 0 to 1 and a reduction from baseline of >=2 points at week 52
- Proportion of patients with an EASI-75 response at week 52
- Change from baseline to week 16 in percent BSA
- Change in SCORAD from baseline to week 16
- Change from baseline to week 16 in global individual AD signs (erythema, infiltration/papulation, excoriations, lichenification)
- Change from baseline to week 16 in DLQI
- Change from baseline to week 16 in HADS
- Reduction in topical AD medication use through week 16
- Proportion of patients with improvement (reduction) of Pruritus NRS ≥3 from baseline to week 52
- Percent change from baseline to week 52 in Pruritus NRS
- Change from baseline to week 52 in percent BSA
- Change in SCORAD from baseline to week 52
- Change from baseline to week 52 in global individual AD signs (erythema, infiltration/papulation, excoriations, lichenification)
- Change from baseline to week 2 in pruritus NRS
- Incidence of skin-infections requiring systemic treatment from baseline through week 56
- Number of flares through week 52
- Incidence of serious treatment-emergent adverse events (TEAEs) from baseline through week 56
- Incidence of TEAEs leading to study drug discontinuation from baseline through week 56 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 16
2) Week 16
3) Week 52
4) Week 52
5) Week 16
6) Week 16
7) Week 16
8) Week 16
9) Week 16
10) Week 16
11) Week 52
12) Week 52
13) Week 52
14) Week 52
15) Week 52
16) Week 2
17) Week 56
18) Week 52
19) Week 56
20) 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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 121 |
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 |
Australia |
Canada |
Croatia |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Latvia |
Netherlands |
New Zealand |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
|
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 | 8 |
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 |