Long-Term Safety and Efficacy Evaluation of Amlitelimab in Participants of Previous Amlitelimab Moderate to Severe Atopic Dermatitis Clinical Trials

Study Overview
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Brief Summary
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This is a single group, Phase 2, long-term extension study for treatment. The purpose of this study is to characterize the safety and efficacy of amlitelimab in treated adult participants with moderate to severe AD who have previously been enrolled in an amlitelimab clinical trial. Visits during the on-treatment period will be at Week 0, 1, 2, 4 and every 4 weeks (Q4W) thereafter. If remote visits are considered appropriate for participants instead of clinic visits at the timepoints indicated in the schedule of activities (SoA) participants/caregivers/legally authorized representatives (LAR) are allowed to perform participant-injections at home according to the schedule of dosing. This decision is at the discretion of the investigator.

Official Title
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A Long-term Extension Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Subcutaneous Amlitelimab in Participants of Previous Amlitelimab Clinical Trials in Moderate to Severe Atopic Dermatitis.

Conditions
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Dermatitis Atopic

Intervention / Treatment
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* Drug: Amlitelimab
* Other: Topical corticosteroids
* Other: Topical calcineurin inhibitors
* Other: Oral corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Participant must be 18 years of age, inclusive, or older at the time of signing the informed consent. Participated in an amlitelimab clinical trial for moderate to severe AD and received study treatment, adequately completed the assessments required for the treatment period. Have reached the rollover timepoint to LTS17367 at the last visit of the treatment period of their parent study SFY17915 Participants in DRI17366 must only be enrolled from 1 of the following 3 groups: The first group: participants at Week 24 in the DRI17336 study who have not achieved an ≥ Eczema Area and Skin Severity Index (EASI)-75 and are Investigator Global Assessment (IGA) ≥ 2. The second group: participants entering LTS17367 between Week 28 and Week 52 of the parent study, due to loss of clinical response in the part 2 of the parent study. Timepoints for entering LTS17367 are Weeks 28, 32, 36, 40, 44, 48 or 52. For DRI17366 loss of clinical response is defined as the first instance of < EASI 50 during the second study period and where rescue therapy is no longer permitted. The third group: participants at Week 24 in DRI17366 who have been re-randomized and who subsequently complete the study to Week 52, enter safety follow-up and experience worsening of their AD during safety follow-up or thereafter Provide signed informed consent and able to comply with the requirements of the protocol Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Developed a medical condition that would preclude participation as described in the permanent discontinuation Known history of or suspected significant current immunosuppression, including history of invasive opportunistic infections or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration History of solid organ or stem cell transplant 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) Participants positive for human immunodeficiency virus; participants with any of the following results at Screening (Visit 1) or at any point during the parent study: presence of HBsAg with or without HBV DNA PCR test, or presence of anti-HBc Ab or presence of anti-HBs Ab with positive HBV DNA PCR test; positive HCVAb confirmed by positive HCV RNA History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator Participants with active 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 Participants with an intermediate or a positive IGRA test are excluded from the study unless all of the following conditions are met: Have a history of prior documented completed chemoprophylaxis for latent TB infection (with a treatment regimen as per local guidelines), OR treated for active TB infection Have been in written form approved for participation in the present trial by a TB specialist who ruled out latent or active TB infection or other mycobacterial infection in the participant For whom review and approval from Sponsor have been granted are eligible Severe concomitant illness that would in the Investigator's opinion inhibit the patient's participation in the study, including for example, but not limited to, hypertension, renal disease, neurological conditions, heart failure and pulmonary disease Skin co-morbidity that would adversely affect the ability to undertake AD assessments Any medical or psychiatric condition which, in the opinion of the Investigator may present an unreasonable risk to the study patient as a result of his/her participation in this clinical study, may make patient's participation unreliable, or may interfere with study assessments In the Investigator's opinion, medical conditions related to prior AD medications that have not healed/fully recovered for more than 2 weeks before screening visit, including, but not limited to, conjunctivitis, keratitis, eosinophilic conditions, arthralgia, herpes zoster, thrombosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amlitelimab<br>Subcutaneous injection Q4W | Drug: Amlitelimab<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous<br>* Other names: SAR445229;Other: Topical corticosteroids<br>* Pharmaceutical form: Topical Route of administration: Topical<br>Other: Topical calcineurin inhibitors<br>* Pharmaceutical form: Topical Route of administration: Topical<br>Other: Oral corticosteroids<br>* Pharmaceutical form: Oral Route of administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who experienced treatment-emergent adverse event (TEAE) | Percentage of participants who experienced TEAE | Baseline to Week 120 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who experienced treatment-emergent SAEs | Percentage of participants who experienced treatment-emergent SAEs | Baseline to Week 120 | 
| Percentage of participants who experienced treatment-emergent adverse events of special interest (AESI) | Percentage of participants who experienced treatment-emergent AESI | Baseline to Week 120 | 
| Absolute change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24 | EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. | DRI17366 Baseline to Week 104 | 
| Percent change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24 | EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. | DRI17366 Baseline to Week 104 | 
| Proportion of participants with EASI75/EASI90/EASI100 from DRI17366 baseline at each LTS17367 visit in participants entering the study from DRI17366 Week 24 | EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline. | DRI17366 Baseline to Week 104 | 
| Proportion of participants with a response of validated investigator global assessment (vIGA-AD) 0 or 1 at each LTS17367 visit in participants entering the study from DRI17366 Week 24 | The IGA is an assessment instrument used to rate the severity of AD globally, based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity. | Baseline to Week 104 | 
| Absolute change from parent study baseline in EASI score at pre-specified timepoints in all participants entering the study | EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. | Baseline to Week 104 | 
| Percent change from parent study baseline in EASI score at pre-specified timepoints in all participants entering the study | EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. | Baseline to Week 104 | 
| Proportion of participants with EASI50/ EASI75/ EASI90/ EASI100 at pre-specified timepoints in all participants entering the studyPercent change from parent study baseline in EASI score at pre-specified timepoints in all participants entering the study | EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. EASI50: >= 50% reduction in score from baseline; EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline. | Baseline to Week 104 | 
| Time to first EASI75/EASI90/EASI100 in those participants who had not achieved it by the time of LTS17367 entry in all participants entering the study | EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline. | Baseline to Week 104 | 
| Time to first remission after LTS17367 enrolment (achieving vIGA-AD 0/1) in those participants who had not achieved vIGA-AD 0/1 by the time of LTS17367 entry in all participants entering the study | The IGA is an assessment instrument used to rate the severity of AD globally, based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity. | Baseline to Week 104 | 
| Proportion of participants with vIGA-AD score 0/1 at each visit in all participants entering the study | The IGA is an assessment instrument used to rate the severity of AD globally, based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity. | Baseline to Week 104 | 
| Proportion of participants with low disease activity state (e.g., vIGA-AD ≤2) at each visit in all participants entering the study | The IGA is an assessment instrument used to rate the severity of AD globally, based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity. | Baseline to Week 104 | 
| Proportion of participants requiring rescue treatment at each visit: all treatments in all participants entering the study | Proportion of participants requiring rescue treatment at each visit: all treatments in all participants entering the study. | Baseline to Week 120 | 
| Proportion of participants requiring rescue treatment at each visit: topical treatments in all participants entering the study | Proportion of participants requiring rescue treatment at each visit: topical treatments in all participants entering the study. | Baseline to Week 120 | 
| Proportion of participants requiring rescue treatment at each visit: systematic treatments in all participants entering the study | Proportion of participants requiring rescue treatment at each visit: systematic treatments in all participants entering the study. | Baseline to Week 120 | 
| Number of days on topical medication (per patient-year) in all participants entering the study | Number of days on topical medication (per patient-year) in all participants entering the study. | Baseline to Week 120 | 
| Change from parent study baseline to prespecified time points through the end of the study: atopic dermatitis control tool (ADCT) in all participants entering the study | ADCT is a six-item patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control. The score ranges from 0-24 with higher scores indicate worsening disease control. | Baseline to Week 104 | 
| Change from parent study baseline to prespecified time points through the end of the study: dermatology life quality index (DLQI) in all participants entering the study | The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL. | Baseline to Week 104 | 
| Change from parent study baseline to prespecified time points through the end of the study: patient oriented eczema measure (POEM) in all participants entering the study | The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a scale ranging from 0 to 4 (0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, 4 = all days). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicated more severe disease and poor quality of life. | Baseline to Week 104 | 
| Serum amlitelimab concentration assessed at prespecified time points through the end of the study | Serum amlitelimab concentration assessed at prespecified time points through the end of the study. | Baseline to Week 104 | 
| Anti-amlitelimab antibody titre in participants with positive response | Anti-amlitelimab antibody titre in participants with positive response. | Baseline to Week 120 | 
| Number of participants with positive anti-drug antibody response | Number of participants with positive anti-drug antibody response. | Baseline to Week 120 |