E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis / Eczema |
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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 |
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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 |
The primary objective of the study is to demonstrate the efficacy of dupilumab monotherapy compared to placebo treatment in adult patients with moderate-to-severe AD. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to assess the safety of dupilumab monotherapy compared to placebo treatment in patients with moderate-to-severe AD. |
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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 sample should be collected on day 1 or at any visit during the study. Blood for RNA sample must be collected before the administration of the first dose of study drug. |
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E.3 | Principal inclusion criteria |
A patient must meet the following criteria to be eligible for inclusion in the study: 1. Male or female, 18 years or older 2. Chronic AD, (according to American Academy of Dermatology Consensus Criteria [Eichenfield 2014]), that has been present for at least 3 years before the screening visit 3. EASI score ≥16 at the screening and baseline visits 4. IGA score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at the screening and baseline visits 5. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits 6. Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks 7. Have applied a stable dose of topical emollient (moisturizer) twice daily for at least 7 days before the baseline visit (NOTE: See exclusion criterion #6 for limitations regarding emollients)
Inclusion criteria 8-10 (see protocol section 4.2) |
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E.4 | Principal exclusion criteria |
A patient who meets any of the following criteria will be excluded from the study: 1. Participation in a prior dupilumab clinical study 2. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit 3. Phototherapy or treatment with immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit 4. Treatment with TCS or TCI within 1 week before the baseline visit 5. Treatment with biologics or live attenuated vaccines within protocol-specified timeframes 6. Active chronic or acute infection requiring systemic treatment within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. 7. Known or suspected history of immunosuppression 8. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening 9. Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit 10. At baseline, presence of any conditions listed as criteria for study drug discontinuation 11. Presence of skin comorbidities that may interfere with study assessments 12. History of malignancy within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin 13. Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization
All the exclusion criteria are listed in protocol section 4.2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of patients with both IGA 0 to 1 (on a 5-point scale) and a reduction from baseline of ≥2 points at week 16 For the European Medicines Agency (EMA) and EMA Reference Market Countries only, the co primary endpoints are: • Proportion of patients with EASI-75 (≥75% improvement from baseline) at week 16 • Proportion of patients with both IGA 0 to 1 (on a 5-point scale) and a reduction from baseline of ≥2 points at week 16
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be determined at week 16. |
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E.5.2 | Secondary end point(s) |
• Proportion of patients with EASI-75 (≥75% improvement from baseline) at week 16 (this is not a secondary endpoint for the EMA as it is already a co-primary endpoint) • 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 • Percent change in EASI score from baseline to week 16 • Change from baseline to week 16 in percent BSA • Change from baseline to week 16 in SCORAD • Change from baseline to week 16 in GISS (erythema, infiltration/papulation, excoriations, lichenification) • Change from baseline to week 16 in DLQI • Change from baseline to week 16 in HADS • Change from baseline to week 16 in POEM • Percent change from baseline to week 2 in pruritus NRS • Incidence of skin infection treatment-emergent adverse events (TEAE) requiring systemic treatment from baseline through week 16 • Incidence of treatment-emergent serious adverse events (TESAEs) from baseline through week 16 • Incidence of TEAEs leading to treatment discontinuation from baseline through week 16 • Overall incidence of TEAEs through week 16
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints will be determined from baseline to week 16. |
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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 | 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) | 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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
Canada |
France |
Germany |
Hong Kong |
Italy |
Korea, Republic of |
Lithuania |
Poland |
Sweden |
United Kingdom |
United States |
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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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Last patient last visit in follow up phase (week 28) |
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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 | 1 |
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 | 1 |
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 |