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A phase 3 study investigating the efficacy, safety, and tolerability of Dupilumab administered to adult patients with severe atopic dermatitis who are not adequately controlled with or are intolerant to oral cyclosporine A, or when this treatment is not medically advisable

Phase 3
Completed
Conditions
atopic dermatitis
eczema
10014982
Registration Number
NL-OMON43809
Lead Sponsor
Regeneron Pharmaceuticals, Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
16
Inclusion Criteria

1. Male or female, 18 years or older ;2. Severe, Chronic AD, (according to American Academy of Dermatology Consensus Criteria [Eichenfield 2014]) ;3. EASI score *20 at the screening and baseline visits ;4. IGA score *3 (on the 0 to 4 IGA scale) 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 TCS;7. Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit;8. Documented history by a physician of either:;A. No prior CSA exposure and not currently a candidate for CSA treatment due to:;* medical contraindications (eg, uncontrolled hypertension on medication), or;* use of prohibited concomitant medications (eg, statins, digoxin, macrolide;* antibiotics, barbiturates, anti-seizure, nonsteroidal anti-inflammatory drugs,;* diuretics, angiotensin-converting-enzyme inhibitors, St John*s Wort, etc), or;* increased susceptibility to CSA-induced renal damage (elevated creatinine) and;* liver damage (elevated function tests), or;* increased risk of serious infections, or ;* hypersensitivity to CSA active substance or excipients, ;OR;B. Previously exposed to CSA, and CSA treatment should not be continued or restarted due to:;* intolerance and/or unacceptable toxicity (eg, elevated creatinine, elevated liver function tests, uncontrolled hypertension, paraesthesia, headache, nausea, hypertrichosis, etc), or;* inadequate response to CSA (defined as flare of AD on CSA tapering after a maximum of 6 weeks of high dose [5 mg/kg/day] to maintenance dose [2 to 3 mg/kg/day] or a flare after a minimum of 3 months on maintenance dose). Flare is defined as increase in signs and/or symptoms leading to escalation of therapy, which can be an increase in dose, a switch to a higher-potency class of TCS, or the start of another systemic non-steroidal immunosuppressive drug. Or;* requirement for CSA at doses >5 mg/kg/day, or duration beyond those specified in the prescribing information (>1 year).

Exclusion Criteria

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, prior to screening;3. Hypersensitivity and/or intolerance to corticosteroids or to any other ingredients contained in the TCS product used in the study;4. Systemic CSA, systemic corticosteroids, or phototherapy within 4 weeks prior to screening, and azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or Janus Kinase (JAK) inhibitors within 8 weeks prior to screening.;5. Treatment with TCI within 1 week prior to screening visit ;6. Treatment with biologics as follows:;* Any cell-depleting agents including but not limited to rituximab: within 6 months before the screening visit, or until lymphocyte count returns to normal, whichever is longer;* Other biologics: within 5 half-lives (if known) or 16 weeks prior to the screening visit, whichever is longer;7. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit ;8. Treatment with a live (attenuated) vaccine within 12 weeks before the screening visit;9. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the screening visit;or superficial skin infections within 1 week before the screening visit. NOTE: patients may be rescreened no sooner than 2 weeks after infection resolves. ;10. 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;11. Presence of any 1 of the following TB criteria: ;a. A positive tuberculin skin test at the screening visit;b. A positive blood QuantiFERON®-TB or T-Spot test at the screening visit;c. Chest x-ray (posterior-anterior and lateral views) at screening or within 3 months before the screening visit (radiology report must be available) with results consistent with prior TB infection (including but not limited to apical scarring, apical fibrosis, or multiple calcified granuloma). This does not include non-caseating granulomata.;NOTE: Any of these 3 TB tests will be performed on a country-by-country basis according to local guidelines only if required by regulatory authorities or ethics boards.;12. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening;13. Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBc Ab), or hepatitis C antibody (HCV Ab) at the screening visit.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Endpoints<br /><br>Primary: The primary endpoint in the study is: the proportion of<br /><br>patients with Eczema Area and Severity Index (EASI) 75 (*75% improvement from<br /><br>baseline) at week 16.</p><br>
Secondary Outcome Measures
NameTimeMethod
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