A Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (AD)

NCT02395133 | Completed Phase 3 Results DMC

• 2 other identifiers: R668-AD-14152014-003384-38
• Study Type: interventional
• Target: 422
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of the study was to assess the ability of different Dupilumab dose regimens, administered as monotherapy, to maintain the treatment response achieved after 16 weeks of initial treatment with Dupilumab monotherapy compared to placebo.

Conditions

Atopic Dermatitis

Keywords

Eczema

Outcome Measures

Primary Outcomes (2)

• Difference Between Current Study Baseline and Week 36 in Percent Change in EASI From Parent Study Baseline (NCT02277743 and NCT02277769)

  The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Difference of percent change in EASI between current study baseline and week 36 in from parent study baseline (NCT02277743 and NCT02277769) was reported. Values after first rescue treatment used were set to missing before multiple imputation (MI).

  Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study)

• Percentage of Participants With Eczema Area and Severity Index >= 75% [EASI-75] at Baseline of Current Study Maintaining EASI-75 at Week 36

  The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved \>=75% overall improvement in EASI score at Week 36. Values after first rescue treatment used were set to missing. Patients with missing value at week 36 were considered as a non-responder.

  Week 36

Secondary Outcomes (18)

• Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response Within 1 Point of Baseline at Week 36

  Baseline, Week 36

• Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response at 0 or 1 Point at Week 36

  Week 36

• Percentage of Participants With Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score Increased by 3 or More Points From Baseline to Week 35

  Baseline up to Week 35

• Time to First Event of Investigator's Global Assessment (IGA) >= 2 for Participants With IGA 0 or 1 at Baseline

  Baseline up to Week 36

• Percentage of Participants With Increased Investigator's Global Assessment (IGA) Score 3 or 4 at Week 36

  Week 36

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Subcutaneous injection of Placebo (for Dupilumab) was administered once weekly (QW) from Week 1 (Day 1) to Week 36.

Drug: Placebo

Dupilumab 300 mg Q8W

EXPERIMENTAL

Subcutaneous injection of Dupilumab 300 milligram (mg) alternatively with placebo (matched to Dupilumab) was administered once every eight week (Q8W) from Week 1 to Week 36.

Drug: Dupilumab

Dupilumab 300 mg Q4W

EXPERIMENTAL

Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered once every four week (Q4W) from Week 1 to Week 36.

Drug: Dupilumab

Dupilumab 300 mg Q2W/QW

EXPERIMENTAL

Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered once every week (QW) or twice a week (Q2W) from Week 1 to Week 36.

Drug: Dupilumab

Interventions

Dupilumab DRUG

Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered.

Also known as: REGN668, SAR231893

Dupilumab 300 mg Q2W/QW; Dupilumab 300 mg Q4W; Dupilumab 300 mg Q8W

Placebo DRUG

Subcutaneous injection of Placebo (for Dupilumab) was administered once weekly (QW).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have completed the treatment phase in 1 of the two 16-week initial treatment studies (R668-AD-1334 or R668-AD-1416).
• Must have achieved at least 1 of the following 2 treatment success criteria:
• Investigator Global Assessment (IGA) = 0 or 1 (clear or almost clear) at week 16 OR Eczema Area and Severity Index \>= 75% (EASI-75) (at least 75% reduction in EASI score from baseline to week 16)
• Must be willing and able to comply with clinic visits and study-related procedures
• Must provide signed informed consent
• Must be able to understand and complete study-related questionnaires

You may not qualify if:

• Receipt of rescue medication for AD in the initial treatment study
• Any conditions that require permanent discontinuation of study treatment in either initial treatment study
• Planned or anticipated major surgical procedure during the participants's participation in this study
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during this study
• Women unwilling to use adequate birth control, if of reproductive potential\* and sexually active. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception, whenever engaging in heterosexual intercourse, throughout the duration of the study and for 120 days after last dose of study drug. These include hormonal contraceptives, intrauterine device, or double barrier contraception (e.g, condom + diaphragm), or a male partner with documented vasectomy. Additional requirements for acceptable contraception may apply in certain countries, based on local regulations. Investigators in these countries will be notified accordingly in a protocol clarification letter.
• (\*For females, menopause is defined as at least 12 consecutive months without menses; if in question, a follicle stimulating hormone level of \>= 25 milli units per milliliter (mU/mL) must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions are not required to use additional contraception).

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Related Publications (3)

• Stander S, Yosipovitch G, Simpson EL, Kim BS, Kabashima K, Thaci D, Metz M, Chen Z, Hagen S, Bastian M. Onset and Long-Term Maintenance of Optimal Itch Response in Adult Patients with Moderate-to-Severe Atopic Dermatitis Treated with Dupilumab: Post Hoc Analysis from Two Phase 3 Trials. Adv Ther. 2025 Apr;42(4):1800-1810. doi: 10.1007/s12325-025-03124-8. Epub 2025 Feb 19.

  PMID: 39969783 DERIVED

• Kamal MA, Kosloski MP, Lai CH, Partridge MA, Rajadhyaksha M, Kanamaluru V, Bansal A, Shabbir A, Shumel B, Ardeleanu M, Richards SM, Yan H, Xu CR, Rodriguez-Marco A, Xiao J, Khokhar FA, Gherardi G, Babilonia E, Maloney J, Mortensen E, Akinlade B, Braunstein N, Stahl N, Torri A, Davis JD, DiCioccio AT. Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis. Front Immunol. 2024 Nov 11;15:1466372. doi: 10.3389/fimmu.2024.1466372. eCollection 2024.

  PMID: 39588375 DERIVED

• Worm M, Simpson EL, Thaci D, Bissonnette R, Lacour JP, Beissert S, Kawashima M, Ferrandiz C, Smith CH, Beck LA, Chan KC, Chen Z, Akinlade B, Hultsch T, Staudinger H, Gadkari A, Eckert L, Davis JD, Rajadhyaksha M, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD, Ardeleanu M. Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Feb 1;156(2):131-143. doi: 10.1001/jamadermatol.2019.3617.

  PMID: 31876900 DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic; Eczema

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Clinical Trial Management
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2015
• First Posted: March 20, 2015
• Study Start: March 25, 2015
• Primary Completion: July 1, 2016
• Study Completion: October 18, 2016
• Last Updated: March 11, 2020
• Results First Posted: October 17, 2018

Record last verified: 2020-02