Open Label, Long-term Study Evaluating Safety and Efficacy of Subcutaneous Amlitelimab in Participants Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis

Phase 2Active Not RecruitingNCT05769777

Sanofi999 enrolled

Overview

This is a single group, 1-arm, long-term safety study for treatment of participants with moderate to severe atopic dermatitis (AD). The purpose of this study is to characterize the long-term safety and efficacy of amlitelimab in treated participants with age ≥12 years old with moderate to severe AD. The study duration per participant will be up to 284 weeks, including: * A screening period of up to 2 to 4 weeks * An open label treatment period of up to 268 weeks (approximately 5 years) * A post-treatment safety follow-up period of at least 20 weeks after the last dose administration (last IMP administration at Week 264) The planned number of visits will be 35 visits.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

999

Conditions

Dermatitis Atopic

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant must be at least 12 years of age inclusive, at the time of signing the informed consent. * Participants must have AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer at baseline. * Participant must have documented history (within 6 months prior to screening visit), of inadequate response (including inadequate efficacy or medical inadvisability) to topical treatments and/or inadequate response to systemic therapies (within 12 months prior to screening visit). * Eczema Area Severity Index (EASI) of 16 or higher at baseline visit/Visit 2. * Validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) of 3 or 4 at baseline visit/Visit 2. * AD involvement of 10% or more of body surface area (BSA) at baseline visit/Visit 2. * Weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) of ≥ 4 at baseline visit/Visit 2. * Able and willing to comply with requested study visits and procedures. * Body weight must be greater than or equal to 25 kg. * Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female participants must not be pregnant or breastfeeding. Exclusion Criteria: * Skin co-morbidity that would adversely affect the ability to undertake AD assessments as per investigator's judgement * Known history of or suspected significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration. * Any malignancies or history of malignancies prior to baseline (except for non-melanoma skin cancer that has been excised and completely cured for more than 5 years prior to baseline). * History of solid organ or stem cell transplant. * Any pre-planned major elective surgery known about at baseline that in the opinion of the investigator would necessitate that IMP be permanently discontinued or require more than three doses to be missed. * Severe concomitant illness that would in the Investigator's opinion inhibit the participant's participation in the study. * Any medical or psychiatric condition which, in the opinion of the Investigator may present an unreasonable risk to the study participants as a result of his/her participation in this clinical study, may make participant's participation unreliable, or may interfere with study assessments. * Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior to baseline (1 week in the event of superficial skin infections); and any infection which as per Investigator's opinion precludes the participant's participation in the study. * Treatment with live (attenuated) vaccines within 12 weeks prior to baseline; failure to complete non-live immunizations required by local regulation (eg, vaccination for COVID-19) at least 14 days prior to baseline. * Having received any of the specified therapy within the specified timeframe(s) prior to the baseline visit. * Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C at the screening visit. * Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection, non-TB mycobacterial infection, or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette-Guérin (BCG)-vaccination within 12 weeks prior to Screening. * In the Investigator's opinion, any clinically significant laboratory results from the clinical chemistry, hematology, coagulation, or urinalysis tests at the screening visit. * In the Investigator's opinion, any significant abnormality on 12-lead electrocardiogram (ECG) at the screening visit that could be suggestive of an unstable or underlying cardio-vascular condition that could preclude the participant's participation in the study. * History of hypersensitivity or allergy to any of the excipients or IMP or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (174)

Allervie Clinical Research - Birmingham- Site Number : 8400050

Birmingham, Alabama, United States

Research Solutions of Arizona- Site Number : 8400020

Litchfield Park, Arizona, United States

Dermatology Trial Associates- Site Number : 8400027

Bryant, Arkansas, United States

University Dermatology Trials- Site Number : 8400052

Newport Beach, California, United States

Children's Hospital Colorado - Aurora- Site Number : 8400041

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs)

Percentage of participants who experienced TEAEs from baseline during the study

Time frame: Baseline up to end of study (EOS) (Week 284)

Percentage of participants who experienced Treatment-Emergent Serious Adverse Events (TESAEs)

Percentage of participants who experienced TESAEs from baseline during the study

Time frame: Baseline up to EOS (Week 284)

Secondary Outcomes

Percentage of participants who experienced Treatment-Emergent Adverse Events of Special Interest (AESI)

Percentage of participants who experienced AESI from baseline during the study

Time frame: Baseline up to EOS (Week 284)

Percentage of participants with Potentially Clinically Significant Abnormalities (PCSA) for vital signs and clinical laboratory assessments, and electrocardiogram (ECG)

Time frame: Baseline up to EOS (Week 284)

Percentage of participants discontinued from study treatment due to Adverse Events (AEs)

Time frame: Baseline up to EOS (Week 284)

Percent change from baseline in Eczema Area and Severity Index (EASI) score

The EASI is an Investigator-assessed tool used to measure the extent (area) and severity of AD. The severity is assessed based on 4 disease characteristics (erythema, induration/papulation, excoriation and lichenification). The extent of involvement of AD is assessed in 4 body regions (head/neck, trunk, upper extremities and lower extremities). Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD.

Time frame: Baseline to EOS (Week 284)

Proportion of participants with at least a 75% reduction from baseline in the EASI (EASI-75)

Time frame: Baseline to EOS (Week 284)

Proportion of participants with at least a 50% reduction from baseline in the EASI (EASI-50)

Time frame: Baseline to EOS (Week 284)

Proportion of participants with at least a 90% reduction from baseline in the EASI (EASI-90)

Time frame: Baseline to EOS (Week 284)

Proportion of participants with at least 100% reduction from baseline in the EASI (EASI-100)

Time frame: Baseline to EOS (Week 284)

Proportion of participants with Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction of ≥2 points from baseline

The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe).

Time frame: Baseline to EOS (Week 284)

Proportion of participants with vIGA-AD 0 (clear) or 1 (almost clear) with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) and a reduction from baseline of ≥2 points

The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe).

Time frame: Baseline to EOS (Week 284)

Proportion of participants with vIGA-AD of 0

The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe).

Time frame: Baseline to EOS (Week 284)

Change in percent Body Surface Area (BSA) affected by AD from baseline

BSA affected by AD will measure the extent (area) of the disease.

Time frame: Baseline to EOS (Week 284)

Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline

The SCORAD Index is a clinical tool used to standardise the evaluation of the extent and severity of AD. To determine the extent of AD, the affected area (A) as a percentage of the whole body is determined, with a maximum score of 100%. The severity (B) of 6 specific symptoms of AD (redness, swelling, oozing/crusting, scratch marks, skin thickening \[lichenification\], dryness \[area where there is no inflammation\]) is assessed on a 4-point scale, with a maximum score of 18: none (0), mild (1), moderate (2) or severe (3). Subjective symptoms (C): itch and sleeplessness are recorded as scored by the participants or relative on a visual analogue scale (VAS), where 0 = no itch (or sleeplessness) and 10 = worst imaginable itch (or sleeplessness), with a maximum possible score of 20.

Time frame: Baseline to EOS (Week 284)

Proportion of participants requiring rescue treatment at each visit

Time frame: Baseline to EOS (Week 284)

Proportion of participants with ≥4-point reduction in weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) from baseline in participants with baseline weekly average of daily PP-NRS ≥4

The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.

Time frame: Baseline to EOS (Week 284)

Proportion of participants with PP-NRS 0 or 1

The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.

Time frame: Baseline to EOS (Week 284)

Percent change in weekly average of daily PP-NRS from baseline

The PP-NRS is a single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD during the past 24 hours, with 0 = no itch and 10 = worst itch imaginable.

Time frame: Baseline to EOS (Week 284)

Change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline

The SP-NRS is a single item 0-10 numeric rating scale assessing skin pain associated with AD during the past 24 hours, with 0 = no pain and 10 = worst possible pain imaginable.

Time frame: Baseline to EOS (Week 284)

Proportion of participants with a reduction in weekly average of daily SP-NRS ≥4 from baseline in participants with baseline weekly average of daily SP-NRS ≥4

The SP-NRS is a single item 0-10 numeric rating scale assessing skin pain associated with AD during the past 24 hours, with 0 = no pain and 10 = worst possible pain imaginable.

Time frame: Baseline to EOS (Week 284)

Change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline

The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD, with 0 being 'no sleep loss related to the symptoms of atopic dermatitis' and 10 being 'I did not sleep at all' due to the symptoms of atopic dermatitis".

Time frame: Baseline to EOS (Week 284)

Proportion of participants with a reduction in weekly average of daily SD-NRS ≥3 from baseline in participants with Baseline weekly average of daily SD-NRS ≥3

Time frame: Baseline to EOS (Week 284)

Change in Patient Oriented Eczema Measure (POEM) from baseline

The POEM is a 7-item self-assessment questionnaire used for monitoring atopic eczema severity, focusing on the signs and symptoms as experienced by the patient during the past 7 days. Total score ranges from 0 to 28.

Time frame: Baseline to EOS (Week 284)

Proportion of participants with a reduction in POEM ≥4 from Baseline in participants with POEM baseline ≥4

Time frame: Baseline to EOS (Week 284)

Proportion of adolescent participants with a reduction in POEM ≥6 from Baseline in adolescents with POEM baseline ≥6

Time frame: Baseline to EOS (Week 284)

Change in Atopic Dermatitis Control Test (ADCT) from baseline

The ADCT is a 6-item patient-reported outcomes instrument with a 7-day recall period to measure AD disease control. Total score ranges from 0 to 24.

Time frame: Baseline to EOS (Week 284)

Proportion of participants with a reduction in ADCT ≥5 from baseline in participants with baseline ADCT≥7

The ADCT is a 6-item patient-reported outcomes instrument with a 7-day recall period to measure AD disease control. Total score ranges from 0 to 24.

Time frame: Baseline to EOS (Week 284)

Change in Dermatology Quality of Life Index (DLQI) from baseline in participants with age ≥16 years old

The DLQI is a 10-item questionnaire to measure dermatology specific quality of life (QoL), covering the participant's previous week (i.e. past 7 days). Total score ranges from 0 to 30, with higher scores indicating greater detrimental impact on QoL.

Time frame: Baseline to EOS (Week 284)

Change in Children's Dermatology Life Quality Index (CDLQI) from baseline in participants with age ≥12 to <16 years old

The CDLQI is a 10-item questionnaire to assess the impact of skin disease on a child's health related quality of life (HRQoL) over a recall period of 1 week. It is validated in children aged 4 to \<16 years. Total score ranges from 0 to 30, with higher scores indicating greater detrimental impact on QoL.

Time frame: Baseline to EOS (Week 284)

Proportion of participants with age ≥12 to <16 with a reduction in CDLQI ≥4 from Baseline in participants with age ≥12 to <16 years old with CDLQI at baseline ≥6

Time frame: Baseline to EOS (Week 284)

Proportion of participants with age ≥12 to <16 with a reduction in CDLQI ≥6 from Baseline in participants with age ≥12 to <16 years old with CDLQI at baseline ≥6

Time frame: Baseline to EOS (Week 284)

Proportion of participants with a reduction in DLQI ≥4 from Baseline in participants with age ≥16 years old and with DLQI at baseline ≥4

Time frame: Baseline to EOS (Week 284)

Change in Patient Global Impression of Severity (PGIS) from baseline

The PGIS is a single item tool used to assess current severity of eczema symptoms, scored on a 5-point scale from 1 = no symptoms to 5 = very severe symptoms.

Time frame: Baseline to EOS (Week 284)

Proportions of participants who report symptoms to be "No" on the PGIS score

The PGIS is a single item tool used to assess current severity of eczema symptoms, scored on a 5-point scale from 1 = no symptoms to 5 = very severe symptoms.

Time frame: Baseline to EOS (Week 284)

Proportions of participants who report symptoms to be "No" or "Mild" on the PGIS score

The PGIS is a single item tool used to assess current severity of eczema symptoms, scored on a 5-point scale from 1 = no symptoms to 5 = very severe symptoms.

Time frame: Baseline to EOS (Week 284)

Proportion of participants who respond "Much better" on the Patient Global Impression of (PGIC) scale

The PGIC is a single item global tool used in the assessment of AD, scored on a 5-point scale from 1 = Much improved to 5 = Much worse.

Time frame: Week 16 to EOS (Week 284)

Proportion of participants who respond "Much better" or "A little better" on the PGIC scale

The PGIC is a single item global tool used in the assessment of AD, scored on a 5-point scale from 1 = Much improved to 5 = Much worse.

Time frame: Week 16 to EOS (Week 284)

Proportion of participants by PGIC responses

The PGIC is a single item global tool used in the assessment of AD, scored on a 5-point scale from 1 = Much improved to 5 = Much worse.

Time frame: Week 16 to EOS (Week 284)

Change in Hospital Anxiety Depression Scale (HADS) from baseline

The HADS is a 14-item patient-reported outcomes measure used to assess states of anxiety and depression over the past week. It is comprised of 7 items assessing anxiety and depression respectively. A Total score is out of 42 (21 per subscale). Higher scores indicate greater levels of anxiety and/or depression.

Time frame: Baseline to EOS (Week 284)

Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A ≥8

Time frame: Baseline to EOS (Week 284)

Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D Baseline ≥8

Time frame: Baseline to EOS (Week 284)