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A Study to Assess the Efficacy and Safety of Dupilumab in Patients With Severe Atopic Dermatitis (AD) That Are Not Controlled With Oral Cyclosporine A (CSA) or for Those Who Cannot Take Oral CSA Because it is Not Medically Advisable

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ClinicalTrials.gov Identifier: NCT02755649
Recruitment Status : Completed
First Posted : April 29, 2016
Last Update Posted : May 11, 2017
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

The main objective of the trial is to evaluate the efficacy of 2 dose regimens of dupilumab compared to placebo, administered with concomitant topical corticosteroids (TCS), in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral Cyclosporine A (CSA), or when this treatment is currently not medically advisable.

The secondary objective is to assess the safety and tolerability of 2 dose regimens of dupilumab compared to placebo, administered with concomitant TCS, in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral CSA, or when this treatment is currently not medically advisable.


Condition or disease Intervention/treatment Phase
Atopic Dermatitis Drug: Dupilumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 325 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 2016
Actual Primary Completion Date : January 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: Dosing regimen 1
Participants in this arm will receive Dupilumab dosing regimen 1
Drug: Dupilumab
Other Name: REGN668/SAR231893

Experimental: Dosing regimen 2
Participants in this arm will receive Dupilumab dosing regimen 2
Drug: Dupilumab
Other Name: REGN668/SAR231893

Experimental: Placebo
Participants in this arm will receive matching placebo
Drug: Placebo



Primary Outcome Measures :
  1. The primary endpoint in the study is the proportion of patients with Eczema Area and Severity Index (EASI) 75 (≥75% improvement from baseline) at week 16 [ Time Frame: Baseline to week 16 ]

Secondary Outcome Measures :
  1. Proportion of patients with EASI 75 (≥75% improvement from baseline) at week 16 for patients with prior CSA use [ Time Frame: Baseline to week 16 ]
  2. Proportion of patients with Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA scale) and a reduction from baseline of ≥2 points at week 16 [ Time Frame: Baseline to week 16 ]
  3. Percent change from baseline to week 16 in the pruritus numerical rating scale (NRS) [ Time Frame: Baseline to week 16 ]
  4. Proportion of patients with improvement (reduction) of pruritus NRS ≥3 at week 16 [ Time Frame: Baseline to week 16 ]
  5. Percent change from baseline to week 16 in the EASI score [ Time Frame: Baseline to week 16 ]
  6. Percent change from baseline to week 16 in percent BSA [ Time Frame: Baseline to week 16 ]
  7. Percent change from baseline to week 16 in the SCORing Atopic Dermatitis (SCORAD) [ Time Frame: Baseline to week 16 ]
  8. Proportion of patients with SCORAD 50 (≥50% improvement from baseline) at week 16 [ Time Frame: Baseline to week 16 ]
  9. Percent change from baseline to week 16 in the Global Individual Signs Score (GISS) (erythema, infiltration/ papulation, excoriations, lichenification) [ Time Frame: Baseline to week 16 ]
  10. Percent change from baseline to week 16 in the Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline to week 16 ]
  11. Percent change from baseline to week 16 in the Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline to week 16 ]
  12. Percent change from baseline to week 16 in the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline to week 16 ]
  13. Percent change from baseline to week 2 in the pruritus NRS [ Time Frame: Baseline to week 2 ]
  14. Mean weekly dose of topical corticosteroids (TCS) through week 16 [ Time Frame: Baseline to week 16 ]
  15. Incidence of skin infection treatment-emergent adverse events (TEAEs) requiring systemic treatment from baseline through the on-treatment period [ Time Frame: Baseline to week 16 ]
  16. Incidence of treatment-emergent serious adverse events (TESAEs) from baseline through the on-treatment period [ Time Frame: Baseline to week 16 ]
  17. Incidence of TEAEs leading to treatment discontinuation from baseline through the on-treatment period [ Time Frame: Baseline to week 16 ]
  18. Overall incidence of TEAEs from baseline through the on-treatment period [ Time Frame: Baseline to week 16 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 18 years or older
  2. Severe, Chronic AD, (according to American Academy of Dermatology Consensus Criteria [Eichenfield 2014]) for whom treatment with potent TCS is indicated
  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:

    1. 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
    2. 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, before the screening visit
  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 before the 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
  9. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the screening 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:

    1. A positive tuberculin skin test at the screening visit
    2. A positive blood QuantiFERON®-TB or T-Spot test at the screening visit
    3. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02755649


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Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02755649     History of Changes
Other Study ID Numbers: R668-AD-1424
First Posted: April 29, 2016    Key Record Dates
Last Update Posted: May 11, 2017
Last Verified: May 2017
Additional relevant MeSH terms:
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Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Cyclosporine
Cyclosporins
Antibodies, Monoclonal
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors