Dupilumab Skin Barrier Function Study in Atopic Dermatitis (BALISTAD)

Sanofi

Status and phase: Completed; Phase 4

Conditions: Atopic Dermatitis

Treatments: Drug: Dupilumab SAR231893

Study type: Interventional

Funder types: Industry

Identifiers

NCT04447417

2020-000314-15 (EudraCT Number)

U1111-1244-1409 (Other Identifier)

LPS15991

Details and patient eligibility

About

Primary Objective:

- Evaluate changes in skin barrier function with transepidermal water loss (TEWL) assessed after skin tape stripping (STS) in pre-defined lesional skin in participants with moderate to severe atopic dermatitis (AD) treated with dupilumab.

Secondary Objectives:

• Evaluate changes in skin barrier function with TEWL assessed after STS in pre-defined lesional and non-lesional skin in participants with moderate to severe AD treated with dupilumab in reference to normal skin of healthy volunteers.
• Evaluate time course of skin barrier function with TEWL assessed before and after STS in pre-defined lesional and non-lesional skin in participants with moderate to severe AD treated with dupilumab in reference to normal skin of healthy volunteers.

Full description

The duration for each participant was a total of approximately 24 weeks.

Enrollment: 52 patients

Sex: All

Ages: 12 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

- Participant must be between 12 to 65 years of age (inclusive), at the time of signing the informed consent.

Atopic dermatitis participants:

• Male or female participants.
• Participants with AD diagnosis according to Hanifin and Rajka criteria at least 1 year before screening.
• Investigator Global Assessment score of >=3 at screening (on the 0-4 scale).
• Participants with moderate to severe atopic dermatitis that were eligible to be treated with dupilumab according to product monograph.
• Participants with AD must have had active lesions on the upper limbs or lower limbs, with severity for lesion erythema or edema/papulation >=2 at screening on the 0-3 scale of the individual signs score.
• Patients must have had a non-lesional (normal looking) skin area 4 centimeters from the edge of the lesional area.
• Were willing to refrain from applying any topical medication products on the target assessment areas (including lesional and non-lesional) throughout the study unless necessary to alleviate intolerable symptoms.
• Were willing to refrain taking showers or soaking in a bathtub with soaps and body washes within 6 hours before TEWL assessments.
• Were willing to apply Cetaphil or Vanicream moisturizer up to twice a day with an exception of moisturizer application on the targeted assessment areas (lesional and non-lesional areas) during the entire study from Day -7 to end of treatment.
• Were willing and able to comply with all clinic visits and study-related procedures.

Healthy volunteers:

• Age and gender matched to a selected AD participant. Adolescents aged 12 to 17 years matched by post puberty status, and adults aged 18 to 65 years were matched by age as close as possible within 10 years of age.
• No current dermatologic or systemic condition that could interfere with the assessments.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of understanding and giving signed informed consent/assent as were described in the protocol, which included compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For adolescents >=12 and <18 years of age a specific ICF must also be signed by the participant's legally authorized representative.

Exclusion criteria:

• Skin conditions other than AD that can confound assessments in the area of TEWL assessments in the opinion of the investigator (i.e., skin atrophy, ichthyosis, Netherton syndrome, severe photo damage).

• Cracked, crusted, oozing, or bleeding AD lesions in the designated lesional assessment area leaving insufficient skin that was adequate for TEWL assessments.

• Hypersensitivity to the active substance or to any of the excipients of dupilumab.

• 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 required daily use of supplemental lubrication; or individuals with ocular conditions that required the use of ocular corticosteroids or cyclosporine.

• Systemic AD treatment or phototherapy within 4 weeks of Baseline.

• Topical AD treatment within 1 week of Baseline. Face and neck may be treated with topical steroids during the washout period if approved by the investigator.

• Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the participant's participation in the study. Examples included, but were not limited to participants with short life expectancy, participants with uncontrolled diabetes (hemoglobin A1c >=9%), participants with cardiovascular conditions (eg, Class III or IV cardiac failure according to the New York Heart Association classification), severe renal conditions (eg, participants on dialysis), hepato-biliary conditions (eg, Child-Pugh class B or C), neurological conditions (eg, demyelinating diseases), active major autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), other severe endocrinological, gastrointestinal, metabolic, pulmonary, psychiatric (known suicidal intentions) or lymphatic diseases. The specific justification for participants excluded under this criterion were noted in study documents (chart notes, electronic case report forms, screening logs, etc.).

• History of hypersensitivity reaction to tape or adhesives.

• Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known) prior to Day 1, whichever was longer.

• Current participation in another investigational clinical study.

• Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who were legally institutionalized.

• Participants were dependent on the Sponsor or Investigator (in conjunction with section 1.61 of the ICH-GCP Ordinance E6).

• Individuals directly involved in the conduct of the study, or immediate family members of such individuals.

• Any specific situation during study implementation/course that might rise ethics considerations.

• Planned or anticipated major surgical procedure during the participant's participation in this study.

• Pregnant or breast feeding women, or were planning to become pregnant or breastfeed during the participant's participation in this study.

• Women unwilling to use adequate birth control, if of reproductive potential* and sexually active. Adequate birth control was defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 12 weeks after last dose of study drug. These included condom, spermicide, hormonal contraceptives, intrauterine device, or double barrier contraception (i.e., condom + diaphragm) or a male partner with documented vasectomy. Additional requirements for acceptable contraception might apply in certain countries, based on local regulations. Investigators in these countries were notified accordingly in a protocol clarification letter.

  *For females, menopause was defined as at least 12 consecutive months without menses; if in question, a follicle stimulating hormone level of >=25 milliunits per milliliter must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions were not required to use additional contraception.

• Healthy volunteers with a personal history of an atopic condition.

• Healthy volunteers with use of any topical treatment anywhere except Cetaphil or Vanicream moisturizer on non-targeted skin areas.

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: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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52 participants in 2 patient groups

Healthy Volunteer

No Intervention group

Description:

Healthy volunteers with age, gender, location of targeted skin lesion area and study site matched to a selected atopic dermatitis (AD) participants, received no treatment, but were monitored in similar way as like enrolled AD participants.

Atopic Dermatitis Patients

Experimental group

Description:

Participants with moderate to severe AD and aged 18 years and older received dupilumab 600 milligrams (mg) (loading dose) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). Participants aged greater than or equal to (\>=) 12 to less than (\<) 18 years received treatment based on their body weight: \<60 kilograms (kg) and \>=60 kg - received dupilumab 400 mg and 600 mg (loading dose) SC injection on Day 1, respectively, followed by dupilumab 200 mg and 300 mg SC injection Q2W through Week 14 (i.e., at Day 15, 29, 43, 57 and 85).

Treatment:

Drug: Dupilumab SAR231893