Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis (DIFFEREN-STAD)

Sanofi

Status and phase: Completed; Phase 4

Conditions: Dermatitis Atopic

Treatments: Drug: Dupilumab (SAR231893)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04823130

2020-003542-36 (EudraCT Number)

U1111-1251-5658 (Other Identifier)

LPS16763

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Healthy Participants: Control

No Intervention group

Description:

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 group

Description:

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.

Treatment:

Drug: Dupilumab (SAR231893)