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

• ClinicalTrials.gov Identifier: NCT04823130
• Recruitment Status: Recruiting
• First Posted: March 30, 2021
• Last Update Posted: September 24, 2021
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Study Description

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

Condition or disease	Intervention/treatment	Phase
Dermatitis Atopic	Drug: Dupilumab SAR231893	Phase 4

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Healthy participants will serve as control group providing normal skin reference for baseline skin biopsy derived endpoints and will be matched for gender, age, race and anatomical site of skin biopsy.
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Multi-center, Exploratory Study to Assess Dupilumab Effect on Pruritus Neuro-mechanisms in Patients With Atopic Dermatitis
• Actual Study Start Date: April 6, 2021
• Estimated Primary Completion Date: July 20, 2022
• Estimated Study Completion Date: August 17, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dupilumab; Double dose on Day 1 and followed by single dose every 2 weeks (Q2W).	Drug: Dupilumab SAR231893; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Other Name: REGN668

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in intraepidermal nerve fiber density [ Time Frame: Baseline to Week 17 ]
   Quantification of intraepidermal nerve fiber density will be calculated by assessing nerve fibers crossing the basement membrane per square millimetre (F/mm2).
2. Change from baseline in nerve fiber branching [ Time Frame: Baseline to Week 17 ]
   Branching of nerve fibers will be assessed semi-quantitatively by classifying patients into 4 groups comprised of only linear, mainly linear, mainly branched or only branched fibers.

Secondary Outcome Measures :

1. Change from baseline in intraepidermal nerve fiber density [ Time Frame: Baseline to Weeks 3 and 21 ]
   Quantification of intraepidermal nerve fiber density will be calculated by assessing nerve fibers crossing the basement membrane per square millimetre (F/mm2).
2. Change from baseline in nerve fiber branching [ Time Frame: Baseline to Weeks 3 and 21 ]
   Branching of nerve fibers will be assessed semi-quantitatively by classifying patients into 4 groups comprised of only linear, mainly linear, mainly branched or only branched fibers.
3. Change from baseline in the outcome of peak pruritus assessed by numeric rating scale (NRS) [ Time Frame: Baseline to Weeks 17 and 21 ]
   The peak pruritus NRS is a simple assessment tool that participants ≥ 12 to <18 years old will use to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the 'worst itch imaginable'.
4. Change from baseline in the outcome of eczema and severity index (EASI) [ Time Frame: Baseline to Weeks 17 and 21 ]
   The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicates worse condition.
5. Change from baseline in the outcome of scoring atopic dermatitis (SCORAD) [ Time Frame: Baseline to Weeks 17 and 21 ]
   SCORAD was used to assess the extent and severity of AD. Extent and severity of eczema as well as subjective assessment of symptoms were assessed and scored. SCORAD total score ranges from 0 (absent disease) to 103 (severe disease).
6. Change from baseline in the outcome of Patient-Reported Outcomes Measurement Information (PROMIS-itch) [ Time Frame: Baseline to Weeks 17 and 21 ]
   PROMIS-itch is an assessment of itch . The short form of following item will be used with no summary score: Itch-severity; activity and clothing; mood and sleep; interference; scratching behavior; quality; trigger.
7. Change from baseline in the outcome of Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline to Weeks 17 and 21 ]
   POEM is a 7-item (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) questionnaire to assess frequency of disease symptoms with a scoring system of 0 to 28. The higher score indicating higher severity.
8. Change from baseline in the outcome of Patient Oriented Eczema Measure Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline to Weeks 17 and 21 ]
   DLQI is a questionaire with a score system of 0 to 30 the high score is indicative of poor QoL.
9. Change from baseline in the outcome of Atopic Dermatitis Control Tool (ADCT) [ Time Frame: Baseline to Weeks 17 and 21 ]
   ADCT is a questionnaire to assess patient-self-perceived control of their eczema with a total score from 0 to 24; higher scores indicate lower AD control.
10. Change from baseline in the outcome of Sleep quality NRS [ Time Frame: Baseline to Weeks 17 and 21 ]
    Sleep quality NRS is a measure asking patients to rate the quality of their sleep using 0 (worst possible sleep) to 10 (best possible sleep) NRS.
11. Change from baseline in the outcome of Skin Pain NRS [ Time Frame: Baseline to Weeks 17 and 21 ]
    Skin pain NRS is a measure asking patients to rate their skin pain using a 0 (No pain) to 10 (worst pain possible) NRS.
12. Change from baseline in the outcome of Skin Sensitivity NRS [ Time Frame: Baseline to Weeks 17 and 21 ]
    Skin sensitivity NRS is a measure asking patient to rate their skin sensitivity to touch using a 0 (Normal) to 10 (extremely sensitive) NRS.
13. Change from baseline in the outcome of Skin Burning NRS [ Time Frame: Baseline to Weeks 17 and 21 ]
    Skin burning NRS is a measure asking patients to rate the burning sensation of thir skin using a 0 (Not at all) to 10 (ver much) NRS.
14. Proportion of AD participants reaching pruritus NRS ≥4 point improvement from baseline [ Time Frame: Baseline to Weeks 3, 5, 9, 17, and 21 ]
15. Incidence of treatment-emergent adverse events [ Time Frame: Baseline to Week 21 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria :

For Atopic dermatitis patients

• Male or female of ≥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.
• Patients 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 atopic dermatitis patients

• 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 patient's participation in the study.
• Patients 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 subject's participation in the study or potentially affect any skin biopsy related read out.
• Positive test for immunoglobulin E (IgE) antibodies.

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

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

Locations

United States, Florida

Investigational Site Number 8400001; Recruiting

Miami, Florida, United States, 33136

United States, New Jersey

Investigational Site Number 8400002; Recruiting

East Windsor, New Jersey, United States, 08520

Germany

Investigational Site Number 2760001; Recruiting

Münster, Germany, 48149

Sponsors and Collaborators

Sanofi

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT04823130
• Other Study ID Numbers: LPS16763; 2020-003542-36 ( EudraCT Number ); U1111-1251-5658 ( Other Identifier: UTN )
• First Posted: March 30, 2021
• Last Update Posted: September 24, 2021
• Last Verified: September 23, 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Dermatitis, Atopic; Dermatitis; Pruritus; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Skin Manifestations