A 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)

• ClinicalTrials.gov Identifier: NCT04417894
• Recruitment Status: Completed
• First Posted: June 5, 2020
• Results First Posted: December 22, 2023
• Last Update Posted: December 22, 2023
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

The primary objective of the study is to assess the efficacy of dupilumab on skin lesions in patients with atopic hand and foot dermatitis.

The secondary objectives of the study are:

• To assess the efficacy of dupilumab on various other domains (pruritus, pain, sleep loss, health related QoL, work life impairment) in patients with atopic hand and foot dermatitis
• To evaluate the safety and tolerability of dupilumab administered to patients with atopic hand and foot dermatitis
• To evaluate systemic exposure and immunogenicity of dupilumab in patients with atopic hand and foot dermatitis

Condition or disease	Intervention/treatment	Phase
Moderate to Severe Atopic Hand and Foot Dermatitis	Drug: dupilumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 14, 2021
• Actual Primary Completion Date: August 31, 2022
• Actual Study Completion Date: November 23, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: dupilumab; Administered subcutaneously (SC) once every 2 weeks (Q2W), following a loading dose on Day 1	Drug: dupilumab; Solution for subcutaneous (SC) injection administration; Other Names: DUPIXENT®; REGN668; SAR231893
Experimental: Matching Placebo; Administered SC Q2W, following a loading dose on Day 1	Drug: Placebo; Solution for SC injection administration

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Hand and Foot Investigator Global Assessment (IGA) 0 or 1 at Week 16 [ Time Frame: At week 16 ]
   IGA is an assessment scale used to determine severity of hand and foot AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Higher score is indicative of more severe disease.

Secondary Outcome Measures :

1. Percentage of Participants 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 [ Time Frame: Baseline to week 16 ]
   Pruritus NRS is an assessment tool that is used to report the intensity of a patient's pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable).
2. Percentage of Participants With Improvement (Reduction) of Weekly Average of Daily Hand and Foot Peak Pruritus NRS ≥3 From Baseline to Week 16 [ Time Frame: Baseline to week 16 ]
   Pruritus NRS is an assessment tool that is used to report the intensity of a patient's pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable).
3. Percent Change From Baseline to Week 16 in Weekly Average of Daily Hand and Foot Peak Pruritus NRS [ Time Frame: Baseline to week 16 ]
   Pruritus NRS is an assessment tool that is used to report the intensity of a patient's pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable).
4. Percent Change in Modified Total Lesion Sign Score (mTLSS) for Hand/Foot Lesions From Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]
   mTLSS combines an evaluation of hand and foot eczema lesions severity; scores are summed, extending from a base estimation of 0 (no signs or symptoms) to the most extreme of 18 (more serious disease).
5. Change From Baseline to Week 16 in Weekly Average of Daily Hand and Foot Peak Pain NRS [ Time Frame: Baseline to week 16 ]
   Pain NRS Scale is an assessment tool used to report the intensity of a participant's pain. Participants will select the number between 0 and 10 that fits best to their worst pain intensity over the past 24 hours (0 = no pain and 10 = the worst pain possible).
6. Mean Change From Baseline to Week 16 in Weekly Average of Daily Sleep NRS [ Time Frame: Baseline to week 16 ]
   Sleep NRS is an 11-point scale (0 to 10) in which 0 indicates worst possible sleep while 10 indicates best possible sleep.
7. Change From Baseline to Week 16 in Percent Surface Area of Hand and Foot Involvement With Atopic Dermatitis (AD) [ Time Frame: Baseline to week 16 ]
8. Percent Change From Baseline to Week 4 in Weekly Average of Daily Hand and Foot Peak Pruritus NRS [ Time Frame: Baseline to week 4 ]
   Pruritus NRS is an assessment tool that is used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable).
9. Percentage of Participants With Improvement (Reduction) of Weekly Average of Daily Hand and Foot Peak Pruritus NRS ≥4 From Baseline to Week 4 [ Time Frame: Baseline to week 4 ]
   Pruritus NRS is an assessment tool that is used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period; maximum itch intensity on a scale of 0 - 10 (0 = no itch; 10 = worst itch imaginable).
10. Percent Change From Baseline to Week 16 in Hand Eczema Severity Index (HECSI) Score in Participants With Hand Dermatitis [ Time Frame: Baseline to week 16 ]
    For participants with hand dermatitis HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). The range for the combined HECSI score is from 0 to 360 (5x6x3x4).
11. Percentage of Participants With HECSI-75 at Week 16 [ Time Frame: At week 16 ]
    HECSI-75 is defined as HECSI score has ≥75% improvement from baseline for participants with hand dermatitis.
12. Percentage of Participants With HECSI-50 at Week 16 [ Time Frame: At week 16 ]
    HECSI-50 is defined as HECSI score has ≥50% improvement from baseline, for participants with hand dermatitis.
13. Percentage of Participants With HECSI-90 at Week 16 [ Time Frame: At week 16 ]
    HECSI-90 is defined as HECSI score has ≥90% improvement from baseline for participants with hand dermatitis.
14. Change From Baseline to Week 16 in Quality of Life in Hand Eczema Questionnaire (QOLHEQ) [ Time Frame: Baseline to week 16 ]
    For participants with hand dermatitis, QOLHEQ is an instrument to assess disease specific Health Related Quality of Life (HRQOL) in those suffering from hand eczema. QOLHEQ overall scoring ranges as follows: 0 (best score) to 117 (worst score).
15. Mean Change From Baseline to Week 16 in Work Productivity and Impairment (WPAI) and Classroom Impairment Questionnaire (CIQ) [ Time Frame: Baseline to week 16 ]
    WPAI + CIQ is a self-administered instrument used to capture the impairment to work productivity/classroom impairment and activity due to atopic hand and foot dermatitis. The WPAI+CIQ yields 4 types of scores: absenteeism, presenteeism, work/classroom productivity loss and activity impairment. All scores range from 0 to 100% with 100% indicating total work/classroom productivity impairment and 0 no impairment at all.
16. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Through Week 16 [ Time Frame: Through week 16 ]
17. Trough Concentration of Functional Dupilumab in Serum at Various Time Points [ Time Frame: Up to week 28 ]
18. Number of Participants With Treatment-Emergent (TE) Anti-Drug Antibody (ADA) [ Time Frame: Up to week 28 ]
19. Number of Participants With Treatment-Emergent ADA by Maximum Titer Category [ Time Frame: Up to Week 28 ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Patients with involvement of at least 2 anatomical areas at screening and baseline
• Patients need to have an IGA hand and foot score of 3 or 4 (moderate-to-severe disease) 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

Key Exclusion Criteria:

• 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

NOTE: Other protocol defined inclusion / exclusion criteria apply

Contacts and Locations

Locations

United States, Alabama

Regeneron Study Site

Birmingham, Alabama, United States, 35209

United States, California

Regeneron Study Site

Redwood City, California, United States, 94063

United States, District of Columbia

Regeneron Study Site

Washington, District of Columbia, United States, 20037

United States, Georgia

Regeneron Study Site

Macon, Georgia, United States, 31217

Regeneron Study Site

Sandy Springs, Georgia, United States, 30328

United States, Indiana

Regeneron Study Site

Columbus, Indiana, United States, 47201

United States, Maryland

Regeneron Study Site

Rockville, Maryland, United States, 20850

United States, Missouri

Regeneron Study Site

Saint Joseph, Missouri, United States, 64506

Regeneron Study Site

Saint Louis, Missouri, United States, 63104

United States, New York

Regeneron Study Site

Kew Gardens, New York, United States, 11415

Regeneron Study Site

Mineola, New York, United States, 11501

United States, North Carolina

Regeneron Study Site

Winston-Salem, North Carolina, United States, 27157

United States, Oregon

Regeneron Study Site

Portland, Oregon, United States, 97239

United States, Texas

Regeneron Study Site

Houston, Texas, United States, 77004

United States, Virginia

Regeneron Study Site

Norfolk, Virginia, United States, 23502

United States, West Virginia

Regeneron Study Site

Morgantown, West Virginia, United States, 26505

United States, Wisconsin

Regeneron Study Site

Milwaukee, Wisconsin, United States, 53226

Germany

Regeneron Study Site

Langenau, Baden Wurttemberg, Germany, 89129

Regeneron Study Site

Frankfurt, Hessen, Germany, 60590

Regeneron Study Site

Augsburg, Germany, 86179

Regeneron Study Site

Berlin, Germany, 10117

Regeneron Study Site

Berlin, Germany, 10789

Regeneron Study Site

Bonn, Germany, 53127

Regeneron Study Site

Dresden, Germany, 01307

Regeneron Study Site

Gera, Germany, 07548

Regeneron Study Site

Kiel, Germany, 24105

Regeneron Study Site

Luebeck, Germany, 23538

Regeneron Study Site

Mahlow, Germany, 15831

Regeneron Study Site

Muenster, Germany, 48149

Japan

Regeneron Study Site

Kawasaki, Kanagawa, Japan, 211-0063

Regeneron Study Site

Sakai, Osaka, Japan, 593-8324

Regeneron Study Site

Shinjuku, Tokyo, Japan, 169-0075

Regeneron Study Site

Tachikawa, Tokyo, Japan, 190-0023

Regeneron Study Site

Kyoto, Japan, 602-8566

Regeneron Study Site

Osaka, Japan, 532-0003

Regeneron Study Site

Tokyo, Japan, 105-0012

Regeneron Study Site

Tokyo, Japan, 143-0023

Poland

Regeneron Study Site

Bialystok, Poland, 15-453

Regeneron Study Site

Chorzow, Poland, 41-516

Regeneron Study Site

Katowice, Poland, 40-648

Regeneron Study Site

Katowice, Poland, 40-851

Regeneron Study Site

Kielce, Poland, 25-155

Regeneron Study Site

Ostrowiec Swietokrzyski, Poland, 27-400

Regeneron Study Site

Warszawa, Poland, 01-142

Regeneron Study Site

Warszawa, Poland, 02-692

Regeneron Study Site

Warszawa, Poland, 02-953

Regeneron Study Site

Wroclaw, Poland, 50-381

Regeneron Study Site

Wroclaw, Poland, 51-318

Sponsors and Collaborators

Regeneron Pharmaceuticals

Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:

Study Protocol  [PDF] January 13, 2021

Statistical Analysis Plan  [PDF] June 27, 2022

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04417894
• Other Study ID Numbers: R668-AD-1924; 2019-003088-22 ( EudraCT Number )
• First Posted: June 5, 2020
• Results First Posted: December 22, 2023
• Last Update Posted: December 22, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Dermatitis; Skin Diseases