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A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF DUPILUMAB IN ADULT AND ADOLESCENT PATIENTS WITH MODERATE-TO-SEVERE ATOPIC HAND AND FOOT DERMATITIS (Liberty-AD-HAFT)

A Study to Evaluate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Moderate-to-Severe Atopic Hand and Foot Dermatitis

133

Baseline characteristics of 133 randomized patients: - Female (83 patients), Male (50 patients) - White (106 patients), Black or African American (7 patients), Asian (17 patients), American Indian or Alaska Native (1 patients), Other (2 patients) - Not Hispanic or Latino (127 patients), Hispanic or Latino (5 patients), Unknown or Not reported (1 patient) - Mean age at baseline (SD) = 34.6 (15.49)

A total of 170 patients were screened, 37 patients failed screening, and 133 patients were randomized. Thirteen of those randomized were from Japan. Of the 37 screen failures: 2 withdrew consent, 33 did not meet inclusion/exclusion criteria, 1 was lost to follow-up and 1 was for an unknown reason.

Serious Adverse Events occurred in: - 1/66 patients in the matching placebo group; 3/67 patients in the dupilumab group Non-serious adverse events at a 5% frequency threshold occurred in: - 34/66 patients in the matching placebo group and 33/67 in the dupilumab group A total of 0 deaths due to any cause occurred in the matching placebo and dupilumab groups Overall rates of adverse events (AEs) were 66% for Dupixent and 74% for placebo. AEs more commonly observed with Dupixent (>=5%) compared to placebo included nasopharyngitis (16% Dupixent, 11% placebo), upper respiratory tract infection (9% Dupixent, 5% placebo), conjunctivitis (6% Dupixent, 2% placebo), herpes viral infections (6% Dupixent, 3% placebo) and increased blood creatine phosphokinase (6% Dupixent, 0% placebo). Additionally, 3% of patients taking Dupixent used at least one rescue medication compared to 21% of patients on placebo.

Percentage of Patients with Hand and Foot Investigator Global Assessment (IGA) 0 or 1 at Week 16 - Matching Placebo: 16.7% of 66 patients, Dupilumab: 40.3% of 67 patients Percentage of Patients with Improvement (Reduction) of Weekly Average of Daily Hand and Foot Peak Pruritus Numerical Rating Scale (NRS) of >=4 Points from Baseline to Week 16 - Matching Placebo: 13.6% of 66 patients, Dupilumab: 52.2% of 67 patients Percentage of Patients with Improvement (Reduction) of Weekly Average of Daily Hand and Foot Peak Pruritus NRS >=3 from Baseline to Week 16 - Matching Placebo: 16.7% of 66 patients, Dupilumab: 61.2% of 67 patients Percent Change from Baseline to Week 16 in Weekly Average of Daily Hand and Foot Peak Pruritus NRS - Matching Placebo: -26.2% (95% Confidence Interval: -38.0 to -14.4) in 66 patients analyzed, Dupilumab: -62.9% (95% Confidence Interval: -74.6 to -51.3) in 67 patients analyzed Percent change in Modified Total Lesion Sign Score (mTLSS) for Hand/Foot Lesions from Baseline to Week 16 - Matching Placebo: -31.0% (-42.6 to -19.4) (66 patients analyzed), Dupilumab: -69.4% (-80.9 to -58.0) (67 patients analyzed) Change from Baseline to Week 16 in Weekly Average of Daily Hand and Foot Peak Pain NRS - Matching Placebo: -1.93 (0.432) (66 patients analyzed), Dupilumab: -4.66 (0.426) (67 patients analyzed) Change from Baseline to Week 16 in Weekly Average of Daily Sleep NRS - Matching Placebo: -0.00 (0.335) (66 patients analyzed), Dupilumab: 0.88 (0.334) (67 patients analyzed) Change from Baseline to Week 16 in Percent Surface Area of Hand and Foot Involvement with Atopic Dermatitis (AD) - Matching Placebo: -10.01 (2.388) (66 patients analyzed), Dupilumab: -16.70 (2.375) (67 patients analyzed) Percent change from baseline to week 4 in weekly average of daily hand and foot peak Pruritus NRS - Matching Placebo: -25.6 (-36.3 to -15.0) (66 patients analyzed), Dupilumab: -47.2 (-57.7 to -36.6) (67 patients analyzed) Percentage of Patients with Improvement (Reduction) of Weekly Average of Daily Hand and Foot Peak Pruritus NRS >=4 from Baseline to Week 4 - Matching Placebo: 9.1% (66 patients analyzed), Dupilumab: 34.3% (67 patients analyzed) Percent Change from Baseline to Week 16 in Hand Eczema Severity Index (HECSI) Score in Patients with Hand Dermatitis - Matching Placebo: -39.9% (6.23) (65 patients analyzed), Dupilumab: -74.8% (6.27) (64 patients analyzed) Percentage of Patients with HECSI-75 at Week 16 - Matching Placebo: 21.5% (65 patients analyzed), Dupilumab: 46.9% (64 patients analyzed) Percentage of Patients with HECSI-50 at Week 16 - Matching Placebo: 30.8% (65 patients analyzed), Dupilumab: 75.0% (64 patients analyzed) Percentage of Patients with HECSI-90 at Week 16 - Matching Placebo: 9.2% (6 out of 65 patients analyzed), Dupilumab: 18.8% (64 patients analyzed) Change from Baseline to Week 16 in Quality of Life in Hand Eczema Questionnaire (QOLHEQ) - Matching Placebo: -16.18 (4.171) (65 patients analyzed), Dupilumab: -40.28 (4.022) (64 patients analyzed) Change from Baseline to Week 16 in Work Productivity and Impairment (WPAI) and Classroom Impairment Questionnaire (CIQ) - Matching Placebo: -21.26 (3.761) (66 patients analyzed), Dupilumab: -36.39 (3.649) (67 patients analyzed) Percentage of Patients with Treatment-Emergent Adverse Events (TEAEs) Through Week 16 - Matching Placebo: 74.2% (66 patients analyzed), Dupilumab: 65.7% (67 patients analyzed) Trough Concentration of Functional Dupilumab in Serum at Various Time Points - Dupilumab 300 mg, Adult Participants: Week 0, 0 mg per L (0) (43 out of 49 patients analyzed), Week 16, 51.2 mg per L (22.0) (48 out of 49 patients analyzed), Week 28, 7.37 mg per L (25.0) (43 out of 49 patients analyzed) - Dupilumab 200 mg, Adolescent Participants: Week 0, 0 mg per L (0) (6 out of 6 patients analyzed), Week 16, 34.0 mg per L (10.7) (6 out of 6 patients analyzed), Week 28, 60 mg per L (84.9) (2 out of 6 patients analyzed) - Dupilumab 300 mg: Adolescent Participants: Week 0, 0 mg per L (0) (6 out of 6 patients analyzed), Week 16, 37.1 mg per L (15.9) (4 out of 6 patients analyzed), Week 28, 7.54 mg per L (16.9) (5 out of 6 patients analyzed) Number of Participants with Treatment-Emergent (TE) Anti-Drug Antibody (ADA) - Matching Placebo: Treatment-Boosted Response: 0 out of 55 patients analyzed, Treatment-Emergent Response: 1 out of 55 patients analyzed - Dupilumab: Treatment-Boosted Response: 0 out of 61 patients analyzed, Treatment-Emergent Response: 8 out of 61 patients analyzed Number of Participants with Treatment-Emergent ADA by Maximum Titer Category - Matching Placebo: Low (<1,000): 1 out of 55 patients analyzed, Moderate (1,000 to 10,000): 0 out of 55 patients analyzed, High (>10,000): 0 out of 55 patients analyzed - Dupilumab: Low (<1,000): 8 out of 61 patients analyzed, Moderate (1,000 to 10,000): 0 out of 61 patients analyzed, High (>10,000): 0 out of 61 patients analyzed

In the trial, patients received Dupixent (n=67) every two weeks (adults 300 mg, adolescents 200 mg or 300 mg based on body weight) or placebo (n=66). At 16 weeks, patients treated with Dupixent experienced the following: - 40% achieved clear or almost clear skin on hands and feet compared to 17% with placebo (p<=0.01), the primary endpoint. - 52% saw a clinically meaningful reduction in itch on hands and feet compared to 14% with placebo (p<0.0001), the key secondary endpoint.

Dec. 05, 2023

Mar. 18, 2023

https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-late-breaking-data-aad-show-significant#:~:text=00%20AM%20EDT-,Dupixent%C2%AE%20(dupilumab)%20Late%2DBreaking%20Da

Yes

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

https://jrct.mhlw.go.jp/latest-detail/jRCT2031200441

Administrator Clinical Trials

Regeneron Pharmaceuticals

777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

clinicaltrials@regeneron.com

Rosario Chikako

Parexel International

Kayabacho First Building, 1-17-21, Shinkawa, Chuo-ku, Tokyo

+81-80-8929-3137

Clinicaltrial-registration@parexel.com

Complete

May. 28, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Patients need to have an IGA hand and foot score of 3 or 4 (moderate-to-severe disease) at screening and baseline
- Patients with involvement of at least 2 anatomical areas at screening and baseline
- Patients with documented recent history (within 6 months before the screening visit) of inadequate response of atopic hand and foot dermatitis to topical medication(s)
- Patients meet the diagnosis criteria for atopic dermatitis (AD)
- Provide informed consent/assent signed by study patient or legally acceptable representative
- Patients need to have been compliant with the skin protection measures through the entire duration of the screening period

- Treatment with dupilumab in the past
- Patients with a positive patch test reaction that are deemed to be clinically relevant as the current cause of the hand and foot dermatitis
- Patients with documented exposure to irritants believed to be a predominant cause of the current hand and foot dermatitis
- Treatment with systemic corticosteroids or non-steroidal immunosuppressive drugs within 4 weeks prior to baseline
- Known history of HIV/HBV/HCV infection
- Pregnant or breastfeeding women or planning to become pregnant or breastfeed during the patient's participation in this study
- Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment and during the study

Both

Moderate-to-Severe Atopic Hand and Foot Dermatitis

Drug: Dupilumab
Solution for subcutaneous (SC) injection administration
Other Names: DUPIXENT, REGN668, SAR231893
Drug: Placebo
Solution for SC injection administration

Proportion of patients achieving an IGA (hand and foot) score of 0 or 1 at week 16

+81-3-5831-0502

April. 30, 2021

United States/ Germany/Poland