Open label, long-term study evaluating safety and efficacy of subcutaneous amlitelimab in adult participants with moderate to severe atopic dermatitis

JRCT ID: jRCT2061220109

Registered date:20/03/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Dermatitis atopic
• Date of first enrollment: 15/03/2023
• Target sample size: 571
• Countries of recruitment: TBD,Japan
• Study type: Interventional

Intervention(s)

Drug: Amlitelimab
Pharmaceutical form: Solution for injection
Route of administration: Subcutaneous (SC)

Drug: Oral corticosteroids
Pharmaceutical form: Oral administration
Route of administration: Oral

Outcome(s)

Primary Outcome

1.Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs)
[Time Frame:Baseline up to end of study (EOS) (Week 176)]
Percentage of participants who experienced TEAEs from baseline during the study
2.Percentage of participants who experienced Treatment-Emergent Serious Adverse Events (TESAEs)
[Time Frame:Baseline up to EOS (Week 176)]
Percentage of participants who experienced TESAEs from baseline during the study

Secondary Outcome

1.Percentage of participants who experienced Treatment-Emergent Adverse Events of Special Interest (AESI)
[Time Frame:Baseline up to EOS (Week 176)]
Percentage of participants who experienced AESI from baseline during the study
2.Percentage of participants with Potentially Clinically Significant Abnormalities (PCSA) for vital signs and clinical laboratory assessments
[Time Frame:Baseline up to EOS (Week 176)]
3.Percentage of participants discontinued from study treatment due to Adverse Events (AEs)
[Time Frame:Baseline up to EOS (Week 176)]
4.Percent change from baseline in Eczema Area and Severity Index (EASI) score
[Time Frame:Baseline to EOS (Week 176)]
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.
5.Proportion of participants with at least a >=75% reduction in EASI score (EASI-75) from baseline
[Time Frame:Baseline to EOS (Week 176)]
EASI75: >= 75% reduction in EASI score from baseline
6.Proportion of participants with EASI-50 /EASI-90 /EASI-100
[Time Frame:Baseline to EOS (Week 176)]
EASI-50: >=50% reduction in EASI score from baseline;
EASI-90: >=90% reduction in EASI score from baseline;
EASI-100: >=100% reduction in EASI score from baseline.
7.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
[Time Frame:Baseline to EOS (Week 176)]
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).
8.Change in percent Body Surface Area (BSA) affected by AD from baseline
[Time Fram:Baseline to EOS (Week 176)]
BSA affected by AD will measure the extent (area) of the disease.
9.Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline
[Time Frame:Baseline to EOS (Week 176)]
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.
10.Proportion of participants requiring rescue treatment at each visit
[Time Frame:Baseline to EOS (Week 176)]
11.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
[Time Frame:Baseline to EOS (Week 176)]
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.
12.Percent change in weekly average of daily PP-NRS from baseline
[Time Frame:Baseline to EOS (Week 176)]
13.Change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline
[Time Frame:Baseline to EOS (Week 176)]
14.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
[Time Frame:Baseline to EOS (Week 176)]
15.Change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline
[Time Frame:Baseline to EOS (Week 176)]
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".
16.Proportion of participants with a reduction in weekly average of daily SD-NRS >=2 from baseline in participants with Baseline weekly average of daily SDNRS >=2
[Time Frame:Baseline to EOS (Week 176)]
17.Change in Patient Oriented Eczema Measure (POEM) from baseline
[Time Frame:Baseline to EOS (Week 176)]
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.
18.Proportion of participants with a reduction in POEM >=4 from Baseline in participants with POEM baseline >=4
[Time Frame:Baseline to EOS (Week 176)]
19.Change in Atopic Dermatitis Control Test (ADCT) from baseline
[Time Frame:Baseline to EOS (Week 176)]
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.
20.Proportion of participants with a reduction in ADCT >=5 from baseline in participants with baseline ADCT >=5
[Time Frame:Baseline to EOS (Week 176)]
21.Change in Dermatology Quality of Life Index (DLQI) from baseline
[Time Frame:Baseline to EOS (Week 176)]
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.
22.Proportion of participants with a reduction in DLQI >=4 from Baseline in participants with DLQI at baseline >=4
[Time Frame:Baseline to EOS (Week 176)]
23.Change in Patient Global Impression of Severity (PGIS) from baseline
[Time Frame:Baseline to EOS (Week 176)]
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.
24.Proportions of participants who report symptoms to be "No" on the PGIS score
[Time Frame:Baseline to EOS (Week 176)]
25.Proportions of participants who report symptoms to be "No" or "Mild" on the PGIS score
[Time Frame:Baseline to EOS (Week 176)]
26.Proportion of participants who respond "Much better" on the Patient Global Impression of (PGIC) scale
[Time Frame:Week 16 to EOS (Week 176)]
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.
27.Proportion of participants who respond "Much better" or "A little better" on the PGIC scale
[Time Frame:Week 16 to EOS (Week 176)]
28.Proportion of participants by PGIC responses
[Time Frame:Week 16 to EOS (Week 176)]
29.Change in Hospital Anxiety Depression Scale (HADS) from baseline
[Time Frame:Baseline to EOS (Week 176)]
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.
30.Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A >=8
[Time Frame:Baseline to EOS (Week 176)]
HADS-A is the anxiety HADS subscale.
31.Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D Baseline >=8
[Time Frame:Baseline to EOS (Week 176)]
HADS-D is the depression HADS subscale.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Participant must be 18 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 either inadequate response or inadvisability of topical treatments.
- Eczema Area Severity Index (EASI) of 16 or higher at baseline visit.
- Validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) of 3 or 4 at baseline visit.
- AD involvement of 10% or more of body surface area (BSA) at baseline visit.
- Weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) of >= 4 at baseline visit.
- Able and willing to comply with requested study visits and procedures.
- 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.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Skin co-morbidity that would adversely affect the ability to undertake AD assessments as per investigator's judgment
- 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 in situ cervical carcinoma that has been excised and cured, or non-melanoma skin cancer that has been excised and cured for more than 3 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 2 weeks prior to baseline (1 week in the event of superficial skin infections); or any active infection (including confirmed Covid-19 infection at screening or baseline) which as per Investigator's opinion inhibit 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, or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette-Guerin (BCG)-vaccination within 12 weeks prior to Screening.
- In the Investigator's opinion, any clinically significant laboratory results from the clinical chemistry, haematology 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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki