Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis

NCT04823130 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: LPS167632020-003542-36U1111-1251-5658
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 3

Brief Summary

Primary Objective: \- Assess change in neuronal architecture following long term treatment with dupilumab in skin biopsies from atopic dermatitis (AD) participants with chronic pruritus. Secondary Objectives:

• Assess change in neuronal architecture following short term treatment with dupilumab and during follow-up in skin biopsies from AD participants with chronic pruritus.
• To evaluate the efficacy of dupilumab in AD participants with chronic pruritus.
• To evaluate the safety of dupilumab in adult participants with moderate-to-severe AD.

Conditions

Dermatitis Atopic

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Week 17

  Skin biopsies were used to analyze the epidermal nerve fiber density. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker protein gene product 9.5 (PGP9.5); and the basement membrane was visualized by staining for collagen type 4. Quantification of intraepidermal nerve fiber density was calculated by assessing nerve fibers crossing the basement membrane per square millimeter (F/mm\^2). Data for this outcome measure was not planned to be collected and analyzed for "healthy participant" arm as pre-specified in protocol.

  Baseline, Week 17

• Percentage of Participants With Change From Baseline in Nerve Fiber Branching on Lesional Skin at Week 17

  Skin biopsies were used to analyze the epidermal nerve fiber branching. Nerve fibers were visualized by staining consecutive sections for the pan-axonal marker PGP9.5; and the basement membrane was visualized by staining for collagen type 4. Branching of epidermal nerve fibers was assessed semi-quantitatively by classifying participants into 4 groups depending on the predominant intraepidermal nerve fiber branching pattern as follows: only linear (100% linear), mainly linear (\>60% linear), mainly branched (\>60% branched), only branched (100% branched). Percentage of participants with change in nerve fiber branching status from baseline on lesional skin at Week 17 are reported in this outcome measure.

  Baseline, Week 17

Secondary Outcomes (14)

• Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Weeks 3 and 21

  Baseline, Weeks 3 and 21

• Change From Baseline in Nerve Fiber Branching on Lesional Skin at Weeks 3 and 21

  Baseline, Weeks 3 and 21

• Change From Baseline in Peak Pruritus Assessed by Numeric Rating Scale (NRS) Scores at Weeks 17 and 21

  Baseline, Weeks 17 and 21

• Change From Baseline in Eczema and Severity Index (EASI) Total Score at Weeks 17 and 21

  Baseline, Weeks 17 and 21

• Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 17 and 21

  Baseline, Weeks 17 and 21

Study Arms (2)

Healthy Participants: Control

NO INTERVENTION

Healthy participants with site, age, gender, race, location of targeted lesional and non-lesional skin area matched to selected AD participants, received no treatment, and were considered as a control group.

Participants With AD: Dupilumab

EXPERIMENTAL

Participants with moderate to severe AD received dupilumab 600 milligrams (mg) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) from Week 3 to Week 15.

Drug: Dupilumab (SAR231893)

Interventions

Dupilumab (SAR231893) DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Also known as: REGN668

Participants With AD: Dupilumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For AD participants
• Male or female of greater than or equal to (\>=)18 years of age inclusive, at the time of signing the informed consent form (ICF).
• Diagnosed with moderate-to-severe chronic AD for at least 1 year before screening.
• Eligible to be treated with dupilumab according to product monograph.
• Pruritus lasting 6 or more weeks before baseline (Day 1).
• Eczema Area and Severity Index (EASI) score \>=12 at baseline.
• Pruritus numerical rating scale (NRS) \>=4 at baseline.
• Investigator global assessment (IGA) score of \>=3 at screening (on the 0 to 4 scale) at baseline.
• Atopic dermatitis active lesions on the upper limbs or lower limbs suitable for a skin biopsy without oozing, bleeding, or infection on upper limbs or trunk.
• Participants with acute AD lesions as determined by Investigator's judgment.
• Stable treatment with non-prohibited medication or therapy during the study.
• For Healthy participants
• Male or female of \>=18 years of age inclusive, at the time of signing the ICF.
• Certified as generally healthy by a comprehensive clinical assessment.

You may not qualify if:

• For AD participants
• Previous treatment with dupilumab stopped within 6 months of baseline due to inadequate response to dupilumab.
• Skin conditions other than AD that can confound assessments in the opinion of the investigator.
• Regular use (\>2 visits per week) of a tanning booth/parlor within 4 weeks of the Screening Visit.
• Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study.
• Participants with active tuberculosis (TB) or non-TB mycobacterial infection, or a history of incompletely treated TB unless it is well documented the participant has been adequately treated and can now start treatment with a biologic agent
• Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period.
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit (Visit 1) or during the Screening Period.
• Known or suspected immunodeficiency, including history of invasive opportunistic infections.
• Active malignancy or history of malignancy within 5 years before the Baseline Visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
• Ocular disorder that in the opinion of the Investigator could adversely affect the individual's risk for study participation. Examples include, but are not limited to, individuals with a history of active cases of herpes keratitis, Sjogren's syndrome, keratoconjunctivitis sicca or dry eye syndrome that require daily use of supplemental lubrication or individuals with ocular conditions that require the use of ocular corticosteroids or cyclosporine.
• History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.
• Participant with any other medical or psychological condition including relevant laboratory or electrocardiogram abnormalities at screening.
• For healthy participants
• Regular use (\>2 visits per week) of a tanning booth/ parlor within 4 weeks of the Screening Visit.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (3)

Investigational Site Number 8400001

Miami, Florida, 33136, United States

Location

Investigational Site Number 8400002

East Windsor, New Jersey, 08520, United States

Location

Investigational Site Number 2760001

Münster, 48149, Germany

Location

Related Links

• LPS16763 Plain Language Results Summary

MeSH Terms

Conditions

Dermatitis, Atopic

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: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Healthy participants served as control group providing normal skin reference for baseline skin biopsy derived outcome measure and were matched for gender, age, race and anatomical site of skin biopsy.

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: March 30, 2021
• Study Start: April 22, 2021
• Primary Completion: June 30, 2022
• Study Completion: August 30, 2022
• Last Updated: September 16, 2025
• Results First Posted: July 11, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); US (2)