Clinical trial NCT01385657: Safety and Tolerability of Dupilumab in Participants With Moderate to Severe Atopic Dermatitis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Sequential Ascending, Repeated-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneous REGN668 in Patients With Moderate-to-Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Dermatitis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2011-06-30
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to end of study (up to Day 85)
Secondary outcomes:
measure: Pharmacokinetics of Dupilumab: Peak Plasma Concentration (Cmax)
timeFrame: Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85
measure: Pharmacokinetics of Dupilumab: Last Positive (Quantifiable) Concentration (Clast)
timeFrame: Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85
measure: Pharmacokinetics of Dupilumab: Time of the Last Positive (Quantifiable) Concentration (Tlast)
timeFrame: Day 22 (pre-dose), 25, 29, 36, 43, 50, 57, 64, 71 and Day 85
Other outcomes:
measure: Percentage of Participants with Investigator's Global Assessment (IGA) Score of "0" or "1" at Day 29/ Week 4 (End of Treatment Period)
timeFrame: At Day 29/ Week 4
measure: Percent Change From Baseline in Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 4
timeFrame: Baseline to Day 29/ Week 4
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 4
timeFrame: Baseline to Day 29/ Week 4
measure: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 4
timeFrame: Baseline to Day 29/ Week 4
measure: Percent Change From Baseline in 5-D Pruritus Scale to Week 4
timeFrame: Baseline to Day 29/ Week 4
measure: Change From Baseline in Average Weekly Pruritus Numerical Rating Scale (NRS) Score to Week 4
timeFrame: Baseline to Day 29/ Week 4
Locations:
city: Kogarah
country: Australia
state: New South Wales
city: Woolloongabba
country: Australia
state: Queensland
city: Carlton
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Hannover
country: Germany
state: Niedersachsen
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Gera
country: Germany
city: Munster
country: Germany
city: Sydenham
country: New Zealand
state: Christchurch
city: Caversham
country: New Zealand
state: Dunedin
city: Auckland
country: New Zealand
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Hamilton JD, Suarez-Farinas M, Dhingra N, Cardinale I, Li X, Kostic A, Ming JE, Radin AR, Krueger JG, Graham N, Yancopoulos GD, Pirozzi G, Guttman-Yassky E. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014 Dec;134(6):1293-1300. doi: 10.1016/j.jaci.2014.10.013.
citation: Beck LA, Thaci D, Hamilton JD, Graham NM, Bieber T, Rocklin R, Ming JE, Ren H, Kao R, Simpson E, Ardeleanu M, Weinstein SP, Pirozzi G, Guttman-Yassky E, Suarez-Farinas M, Hager MD, Stahl N, Yancopoulos GD, Radin AR. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014 Jul 10;371(2):130-9. doi: 10.1056/NEJMoa1314768.