Safety and Tolerability of Dupilumab in Participants With Moderate to Severe Atopic Dermatitis

Phase 1

Completed

• Conditions: Atopic Dermatitis
• Interventions: Drug: Placebo; Drug: Dupilumab; Other: Background treatment

• Registration Number: NCT01385657
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

The purpose of this study is to assess the safety and tolerability of repeated subcutaneous (SC) doses of Dupilumab in participants with moderate-to-severe atopic dermatitis (AD).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-06-09
• Study First Submitted QC: 2011-06-28
• Study First Posted: 2011-06-30
• Study Start: 2011-07-31
• Primary Completion: 2012-03-31
• Study Completion: 2012-03-31
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-24
• Last Update Posted: 2020-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

1. Male or female, 18 years or older;
2. Chronic AD diagnosed by the Eichenfield revised criteria of Hannifin and Rajka that had been present for at least 3 years before the screening visit;
3. Eczema Area and Severity Index (EASI) score ≥ 12 at the screening and baseline visits;
4. Investigator's Global Assessment (IGA) score ≥ 3 at the screening and baseline visits;
5. ≥ 10% body surface area (BSA) of AD involvement at the screening and baseline visits;
6. History of inadequate response to a stable (≥ 1 month) regimen of topical corticosteroids or calcineurin inhibitors as treatment for AD within 3 months before the screening visit.

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Exclusion Criteria

1. Positive Hepatitis B surface antigen, and/or positive Hepatitis C antibody at the screening visit;
2. Treatment with an investigational drug within 8 weeks or within 5 half-lives, if known, whichever is longer, before the baseline visit;
3. Treatment with leukotriene inhibitors within 4 weeks before the baseline visit;
4. Treatment with systemic corticosteroids within 4 weeks before the baseline visit;
5. Treatment with topical corticosteroids, tacrolimus, and/or pimecrolimus within 1 week before the baseline visit;
6. Systemic treatment for AD with an immunosuppressive/immunomodulating substance within 4 weeks before the baseline visit;
7. Chronic or acute infection requiring treatment with oral or IV antibiotics, antivirals, or antifungals within 4 weeks before the screening visit or superficial skin infections within 1 week before the screening visit;
8. Known history of human immunodeficiency virus (HIV) infection;
9. History of clinical parasite infection, other than treated trichomoniasis;
10. History of malignancy within 5 years before the baseline visit, with the following exceptions: participants with a history of completely treated carcinoma in-situ of cervix, and non-metastatic squamous or basal cell carcinoma of the skin were allowed;
11. Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor's medical monitor, would place the participant at risk, interfere with participation in the study, or interfere with the interpretation of study results;
12. Pregnant or breast-feeding women;
13. Unwilling to use adequate birth control, if of reproductive potential and sexually active.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo (for Dupilumab) as a single subcutaneous (SC) injection on Day 1, 8, 15, and 22
Dupilumab 150 mg	Background treatment	Dupilumab 150 mg as a single SC injection on Day 1, 8, 15, and 22
Dupilumab 300 mg	Background treatment	Dupilumab 300 mg as a single SC injection on Day 1, 8, 15, and 22
Dupilumab 300 mg	Dupilumab	Dupilumab 300 mg as a single SC injection on Day 1, 8, 15, and 22
Dupilumab 150 mg	Dupilumab	Dupilumab 150 mg as a single SC injection on Day 1, 8, 15, and 22
Placebo	Background treatment	Placebo (for Dupilumab) as a single subcutaneous (SC) injection on Day 1, 8, 15, and 22

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	Baseline up to end of study (up to Day 85)	An adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study visit \[Day 85\]). Any TEAE included participants with both serious and non-serious AEs.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of Dupilumab: Time of the Last Positive (Quantifiable) Concentration (Tlast)	Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85	Mean time of last measurable concentration of Dupilumab in actual days.
Pharmacokinetics of Dupilumab: Peak Plasma Concentration (Cmax)	Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85	Maximum Plasma Concentration of functional Dupilumab observed following the fourth (last) dose.
Pharmacokinetics of Dupilumab: Last Positive (Quantifiable) Concentration (Clast)	Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85	Last Positive (Quantifiable) Concentration of Dupilumab.