A study to confirm the efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis (AD)

Phase 1

• Conditions: Atopic dermatitis; MedDRA version: 18.0Level: LLTClassification code 10003639Term: Atopic dermatitisSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2014-002619-40-DE
• Lead Sponsor: Regeneron Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-07
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

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)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 550
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

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-?, 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 antifungalswithin 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: 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.;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<br>For the EU and EU reference market countries, and Japan only, the co primary endpoints are:<br>• Proportion of patients with EASI-75 (=75% improvement from baseline) at week 16<br>• 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<br>;Timepoint(s) of evaluation of this end point: The primary endpoint will be determined at week 16.