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 | 19.0 |
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. Baseline Pruritus Numerical Rating Scale (NRS) average score for maximum itch intensity ≥3 NOTE: Baseline Pruritus NRS average score for maximum itch intensity will be determined based on the average of daily NRS scores for maximum itch intensity (the daily score ranges from 0 to 10) during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of the 7 days is required to calculate the baseline average score. For patients who do not have at least 4 daily scores reported during the 7 days immediately preceding the planned randomization date, randomization should be postponed until this requirement is met, but without exceeding the 35-day maximum duration for screening. 7. 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 8. Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit (NOTE: See exclusion criterion #6 for limitations regarding emollients)(See background treatment with topical emollient in section 5.2.)
Inclusion criteria 9-11 (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.Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment: •Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.) •Phototherapy for AD 4.Treatment with TCS or TCI within 1 week before the baseline visit 5.Treatment with biologics as follows: •Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever is longer • Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever is longer 6.Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (patients may continue using stable doses of such moisturizers if initiated before the screening visit) 7.Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the baseline visit 8.Planned or anticipated use of any prohibited medications (see section 5.7.1) and procedures during study treatment 9.Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit 10.Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. NOTE: patients may be rescreened after infection resolves. 11.Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment 12.History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening 13.Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody at the screening visit
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 EU and EU reference market countries, and Japan 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) |
The key secondary endpoints are:
•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
Other secondary endpoints are:
•Percent change in EASI score from baseline to week 16 •Change from baseline to week 16 in percent BSA •Percent change from baseline to week 16 in SCORAD •Percent 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 POEM •Change from baseline to week 16 in HADS •Percent change from baseline to week 2 in pruritus NRS •Incidence of treatment-emergent serious adverse events (TESAEs) from baseline through week 16 •Incidence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation from baseline through week 16 •Overall incidence of TEAEs through week 16 •Incidence of skin infection TEAEs requiring systemic treatment from baseline 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 | 20 |
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 | 2 |
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 |