Dermatitis Atopic
Conditions
Brief summary
This is a parallel, Phase 2b, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy, safety, and tolerability of lunsekimig monotherapy in adult participants (aged 18 to 80 years, inclusive) with moderate-to-severe atopic dermatitis (AD). This study explores the efficacy and safety of 3 subcutaneous (SC) dose regimens of lunsekimig in adult participants with moderate-to-severe AD who have a documented history, within 6 months prior to baseline, of an inadequate response to topical treatments or for whom topical therapies are not advised. The study consists of 6 arms: 3 parallel dosing regimens and matching placebo arms. Additionally, participants have the option of engaging in a dense pharmacokinetic/pharmodynamic (PK/PD) sampling subgroup. The study duration will be up to approximately 36 weeks, including up to 4 weeks of screening, 24 weeks of treatment period and an 8-week safety follow-up period.
Interventions
DRUGLunsekimig
Pharmaceutical form: Solution for injection in vial Route of administration: Subcutaneous injection
DRUGPlacebo
Pharmaceutical form: Solution for injection in vial Route of administration: Subcutaneous injection
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants must be 18 to 80 years of age, inclusive, at the time of signing the informed consent. * Diagnosis of Atopic Dermatitis (AD) as defined by the American Academy of Dermatology (AAD) clinical guidelines (2023) for 1 year or longer at baseline (Day 1) * Documented history within 6 months prior to Screening Visit, of either inadequate response or inadvisability of topical treatments * Eczema Area and Severity Index (EASI) score of 16 or higher (range, 0 to 72) at baseline (Day 1) * Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score of 3 or 4 at baseline visit (Day 1) (on the 0 to 4 vIGA-AD scale, a vIGA-AD score of 3 and 4 represents moderate and severe, respectively). * AD involvement of 10% or more of Body Surface Are (BSA) at baseline (Day 1) * Weekly average of daily Peak Pruritis-Numerical Rating (PP-NRS) score of ≥4 at baseline (Day 1) * Must have applied a stable dose of topical bland emollient (simple moisturizer, no additives \[eg, urea\]) at least once daily for a minimum of 5 out of 7 consecutive days before baseline (Day 1).
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * Skin comorbidity that would adversely affect the ability to undertake AD assessments (eg, psoriasis, tinea corporis, and lupus erythematosus) according to the Investigator's judgment. * Known history of, or suspected, significant current immunosuppression NOTE: The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in Eczema Area and Severity Index (EASI) score from baseline to Week 24 | From Baseline throughout the study, up to Week 24 | Eczema Area and Severity index is an Investigator-assessed validated tool used to measure the extent (area) and severity of atopic dermatitis (AD). Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving EASI-75 at Week 24 | From Baseline throughout the study, up to Week 24 | EASI 75 is defined by reduction of EASI score by ≥75% from baseline |
| Proportion of participants with a Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear) and a reduction from Baseline of ≥2 points at Week 24 | From Baseline throughout the study, up to Week 24 | The Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score is a 5-point scale used to determine severity of AD and clinical response to treatment, ranging from 0 (clear) to 4 (severe). |
| Proportion of participants with reduction (improvement) of ≥4 in the weekly average of daily Peak Pruritis-Numerical Rating Scale (PP-NRS) score from Baseline to Week 24 | From Baseline throughout the study, up to Week 24 | The Peak Pruritis-Numerical Rating Scale (PP-NRS) is a validated single-item patient-reported outcome (PRO) to assess worst itch intensity on a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable". |
| Absolute change from Baseline in EASI score at Week 24 | From Baseline throughout the study, up to Week 24 | Eczema Area and Severity index is an Investigator-assessed validated tool used to measure the extent (area) and severity of atopic dermatitis (AD). Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. |
| Percent change from Baseline in EASI score throughout the study | From Baseline throughout the study, up to Week 24 | Eczema Area and Severity index is an Investigator-assessed validated tool used to measure the extent (area) and severity of atopic dermatitis (AD). Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. |
| Proportion of participants with a vIGA-AD score of 0 (clear) or 1 (almost clear) at Week 24 | From Baseline throughout the study, up to Week 24 | The Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score is a 5-point scale used to determine severity of AD and clinical response to treatment, ranging from 0 (clear) to 4 (severe). |
| Proportion of participants with a response of vIGA-AD 0 or 1 and a reduction from Baseline of ≥2 points throughout the study | From Baseline throughout the study, up to Week 24 | The Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score is a 5-point scale used to determine severity of AD and clinical response to treatment, ranging from 0 (clear) to 4 (severe). |
| Percent change in the weekly average of daily PPNRS scores from Baseline to Week 24 | From Baseline throughout tje study, up to Week 24 | The Peak Pruritis-Numerical Rating Scale (PP-NRS) is a validated single-item patient-reported outcome (PRO) to assess worst itch intensity on a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable". |
| Percent change in the weekly average of daily sleep disturbance NRS score from Baseline to Week 24 | From Baseline throughout the study, up to Week 24 | The Sleep Disturbance-Numerical Rating Scale (SD-NRS) is a validated single item 0-10 numerical rating scale assessing sleep disturbance associated with AD, with 0 being 'no sleep loss related to the symptoms of AD' and 10 being 'I did not sleep at all' due to the symptoms of AD. |
| Percent change in the weekly average of daily skin pain NRS score from Baseline to Week 24 | From Baseline throughout the study, up to Week 24 | The Skin Pain-NRS is a whole number scale ranging from 0 to 10 with a 24-hour recall period, with 0 = no pain and 10 = worst possible pain imaginable. The threshold for determining clinically meaningful change is ≥ 4-point change in the weekly average SP-NRS. |
| Change in percent Body Surface Area (BSA) affected by Atopic Dermatitis from Baseline to Week 24. | From Baseline throughout the study, up to Week 24 | The BSA affected by AD will be assessed in 4 body regions: head/neck, trunk (including the genitals), upper extremities, and lower extremities (including the buttocks). Each body region should be evaluated from 0 to 100%. The percentage of the affected area will be multiplied by the proportion of that body region to the whole body. |
| Proportion of participants achieving EASI-50 at Week 24 | From Baseline throughout the study, up to Week 24 | EASI-50 is defined by reduction of EASI score by ≥50% from baseline. |
| Proportion of participants achieving EASI-90 at Week 24 | From Baseline throughout the study, up to Week 24 | EASI-90 is defined by reduction of EASI score by ≥90% from baseline. |
| Proportion of participants with improvement (reduction) of ≥4 points in the weekly average of daily PP NRS scores from Baseline throughout the study | From Baseline throughout the study, up to Week 24 | The Peak Pruritis-Numerical Rating Scale (PP-NRS) is a validated single-item patient-reported outcome (PRO) to assess worst itch intensity on a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable". |
| Proportion of participants with improvement (reduction) of ≥4 points in the weekly average of daily SD-NRS scores from Baseline to Week 24, in participants with a baseline weekly average of daily SD-NRS scores of ≥4 points | From Baseline throughout the study, up to Week 24 | The Sleep Disturbance-Numerical Rating Scale (SD-NRS) is a validated single item 0-10 numerical rating scale assessing sleep disturbance associated with AD, with 0 being 'no sleep loss related to the symptoms of AD' and 10 being 'I did not sleep at all' due to the symptoms of AD. |
| Proportion of participants with improvement (reduction) of ≥4 points in the weekly average of daily Skin Pain NRS scores from Baseline to Week 24, in participants with a baseline weekly average of daily Skin Pain NRS scores of ≥4 points | From Baseline throughout the study, up to Week 24 | The Skin Pain--Numerical Rating Scale (SP-NRS) is a whole number scale ranging from 0 to 10 with a 24-hour recall period, with 0 = no pain and 10 = worst possible pain imaginable. The threshold for determining clinically meaningful change is ≥ 4-point change in the weekly average SP-NRS. |
| Percent change in Scoring of Atopic Dermatitis (SCORAD) Index from Baseline to Week 24 | From Baseline throughout the study, up to Week 24 | The Scoring of Atopic Dermatitis (SCORAD) Index is a validated clinical tool that was developed to standardize the evaluation of the extent and severity of AD. Total score ranges from 0 (absent disease) to 103 (severe disease). |
| Proportion of participants with an improvement of ≥4 points in Dermatology Life Quality Index (DLQI) score from Baseline to Week 24 and throughout the study | From Baseline throughout the study, up to Week 24 | The Dermatology Life Quality Index (DLQI) is a 10-item dermatology specific health-related quality of life (HRQoL) questionnaire. The total score is correlated to the detrimental effect of AD on QoL and ranges from 0 to 30, with a higher score indicating a poorer QoL. |
| Percent change in Dermatology Life Quality Index (DLQI) score from Baseline to Week 24 and throughout the study | From Baseline throughout the study, up to Week 24 | The Dermatology Life Quality Index (DLQI) is a 10-item dermatology specific health-related quality of life (HRQoL) questionnaire. The total score is correlated to the detrimental effect of AD on QoL and ranges from 0 to 30, with a higher score indicating a poorer QoL. |
| Percent change in Patient Oriented Eczema Measure (POEM) score from Baseline to Week 24 | From Baseline throughout the study, up to Week 24, | The Scoring of Atopic Dermatitis (SCORAD) Index is a validated clinical tool that was developed to standardise the evaluation of the extent and severity of AD. |
| Percent change in Hospital Anxiety and Depression Scale (HADS) from Baseline to Week 24 | From Baseline throughout the study, up to to Week 24 | The Hospital Anxiety and Depression Scale (HADS) is a 14-item patient-reported outcome (PRO) questionnaire used to assess states of anxiety and depression over the past week with two subscales. Each subscale (anxiety \& depression) ranges 0-21. The total HADS score ranges 0-42 with higher score indicating a poorer state. |
| Incidence of Antidrug antibody (ADA) against lunsekimig up to end of study | From Baseline throughout the study, up to Week 32 | — |
| Serum concentrations of lunsekimig throughout the study | From Baseline throughout the study, up to Week 32 | — |
| Serum concentrations of lunsekimig in the pharmacokinetic/pharmacodynamics (PK/PD) subgroup throughout the study | From Baseline throughout the study, up to Week 32 | — |
| Number of participants with treatment-emergent adverse events (TEAEs), including local reactions, adverse events of special interest (AESIs), and serious adverse events (SAEs) | From Baseline throughout the study, up to Week 32 | — |
Countries
Czechia, Japan, Poland, United States
Outcome results
None listed