Clinical trial NCT04823130: Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis
Official title: A Multi-center, Exploratory Study to Assess Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dermatitis Atopic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2021-03-30
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

Detailed description: AD participants: A 20-week Observation Period including 16 weeks of treatment for AD participants and a 4-week follow-up period; Healthy participants: 8 days observation period.

Eligibility criteria: Inclusion criteria:

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.

Exclusion criteria:

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.
* Treatment with the following concomitant medications and procedures is prohibited within 4 weeks before the Screening Visit or 5 half-lives (whichever is longer) until End of Study Visit:

  * Topical medication
  * Analgesics
  * Immunomodulators
  * Antidepressants
  * Anti-anxiety drugs
* Any Type 2 immune disorders uncontrolled Type 2 diabetes mellitus, Type 1 diabetes mellitus, neuropathy or any other neurological disease.
* Any concomitant illness(es) or conditions that, in the Investigator's judgment, would adversely affect the participant's participation in the study or potentially affect any skin biopsy related read out.
* Positive test for immunoglobulin E (IgE) antibodies.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Week 17
timeFrame: Baseline, Week 17
measure: Percentage of Participants With Change From Baseline in Nerve Fiber Branching on Lesional Skin at Week 17
timeFrame: Baseline, Week 17
Secondary outcomes:
measure: Change From Baseline in Intraepidermal Nerve Fiber Density on Lesional Skin at Weeks 3 and 21
timeFrame: Baseline, Weeks 3 and 21
measure: Change From Baseline in Nerve Fiber Branching on Lesional Skin at Weeks 3 and 21
timeFrame: Baseline, Weeks 3 and 21
measure: Change From Baseline in Peak Pruritus Assessed by Numeric Rating Scale (NRS) Scores at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Eczema and Severity Index (EASI) Total Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Patient-Reported Outcomes Measurement Information (PROMIS-itch) Itch-Severity Total Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Atopic Dermatitis Control Tool (ADCT) Total Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Sleep Quality Numerical Rating Scale Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Skin Pain Numerical Rating Scale Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Skin Sensitivity Numerical Rating Scale Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Change From Baseline in Skin Burning Numerical Rating Scale Score at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
measure: Percentage of Participants With Change of Greater Than or Equal to (>=4) Point in Pruritus Numerical Rating Scale From Baseline at Weeks 17 and 21
timeFrame: Baseline, Weeks 17 and 21
Other outcomes:
Locations:
city: Miami
country: United States
facility: Investigational Site Number 8400001
state: Florida
city: East Windsor
country: United States
facility: Investigational Site Number 8400002
state: New Jersey
city: Münster
country: Germany
facility: Investigational Site Number 2760001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: