Long-Term Safety and Efficacy Evaluation of amlitelimab in adult participants with moderate to severe atopic dermatitis

JRCT ID: jRCT2031220522

Registered date:20/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Dermatitis atopic
• Date of first enrollment: 01/01/2023
• Target sample size: 300
• Countries of recruitment: Australia,Japan,Bulgaria,Japan,Hungary,Japan,Poland,Japan,Spain,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Amlitelimab
Solution for injection Subcutaneous

Outcome(s)

Primary Outcome

1. Percentage of participants who experienced treatment-emergent adverse event (TEAE) from baseline during the study
[Time Frame baseline:Baseline to Week 120]

Secondary Outcome

1. Percentage of participants who experienced treatment-emergent SAEs from baseline during the study
[Time Frame baseline:Baseline to Week 120]
2. Percentage of participants who experienced treatment-emergent adverse events of special interest (AESI) from baseline during study
[Time Frame baseline:Baseline to Week 120]
3 .Absolute change from KY1005-CT05 (DRI17366) baseline in EASI score at each visit in participants entering the study from KY1005-CT05 (DRI17366) Week 24
[Time Frame baseline:DRI17366 Baseline to Week 104]
*1) 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.
4. Percent change from KY1005-CT05 (DRI17366) baseline in EASI score at each visit in participants entering the study from KY1005-CT05 (DRI17366) Week 24
[Time Frame baseline:DRI17366 Baseline to Week 104]
For EASI, see "Secondary Outcome-3. *1"
5.Proportion of participants with EASI75/EASI90/EASI100 from KY1005-CT05 (DRI17366) baseline at each visit in participants
entering the study from KY1005-CT05 (DRI17366) Week 24
[Time Frame baseline:DRI17366 Baseline to Week 104]
For EASI, see "Secondary Outcome-3. *1"
EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline.
6. Proportion of participants with a response of
investigator global assessment (IGA) 0 or 1and a reduction from baseline of >=2 points at each visit in participants entering the study from KY1005-CT05 (DRI17366) Week 24
[Time Frame baseline:Baseline to Week 104]
*2) 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.
7. Absolute change from LTE baseline in EASI score at pre-specified timepoints in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
For EASI, see "Secondary Outcome-3. *1"
8. Percent change from LTE baseline in EASI score at pre-specified timepoints in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
For EASI, see "Secondary Outcome-3. *1"
9. Proportion of participants with EASI50/EASI75/EASI90/EASI100 at pre-specified timepoints in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
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.
10. Time to first EASI75/EASI90/EASI100 in those participants who had not achieved it by the time of LTE entry in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
For EASI, see "Secondary Outcome-3. *1"
EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline.
11. Time to first remission after LTE enrolment (achieving IGA 0/1) in those participants who had not achieved IGA 0/1 by the time of LTE entry in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
For IGA, see "Secondary Outcome-6. *2"
12. Proportion of participants with IGA score 0/1 at each visit in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
For IGA, see "Secondary Outcome-6. *2"
13. Proportion of participants with low disease activity state (e.g., IGA <=2) at each visit in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
For IGA, see "Secondary Outcome-6. *2"
14. Proportion of participants requiring rescue treatment at each visit: all treatments in all participants entering the study
[Time Frame baseline:Baseline to Week 120]
15. Proportion of participants requiring rescue treatment at each visit: topical treatments in all participants entering the study
[Time Frame baseline:Baseline to Week 120]
16. Proportion of participants requiring rescue treatment at each visit: systematic treatments in all participants entering the study
[Time Frame baseline:Baseline to Week 120]
17. Number of days on topical medication (per patient-year) in all participants entering the study
[Time Frame baseline:Baseline to Week 120]
18. Change from LTE baseline to prespecified time points through the end of the study: atopic dermatitis control tool (ADCT) in all participants
entering the study
[Time Frame baseline:Baseline to Week 104]
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.
19. Change from LTE baseline to prespecified time points through the end of the study: dermatology life quality index (DLQI) in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
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.
20. Change from LTE baseline to prespecified time points through the end of the study: patient oriented eczema measure (POEM) in all participants entering the study
[Time Frame baseline:Baseline to Week 104]
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.
21. Serum amlitelimab concentration assessed at prespecified time points through the end of the study
[Time Frame baseline:Baseline to Week 104]
22. Anti-amlitelimab antibody titre in participants with positive response
[Time Frame baseline:Baseline to Week 120]
23. Number of participants with positive anti-drug antibody response
[Time Frame baseline:Baseline to Week 120]

Key inclusion & exclusion criteria

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

Include criteria

- Participant must be 18 years of age, inclusive, or older at the time of signing the informed consent.
- Participated in KY1005-CT05 (DRI17366) for moderate to severe AD and received study treatment, adequately completed the assessments required for the treatment period. Participants must only be enrolled from 1 of the following 3 groups:
- - The first group: participants at Week 24 in the KY1005-CT05 (DRI17336) study who have not achieved an >= Eczema Area and Skin Severity Index (EASI)-75 and are Investigator Global Assessment (IGA) 2, 3 or 4.
- - The second group: participants entering the LTE between Week 28 and Week 52 of the parent study, due to loss of clinical response in the part 2 of the parent study. Loss of clinical response is defined as the first instance of < EASI-50 during the second study period.
- - The third group: participants at Week 24 in KY1005-CT05 (DRI17336) 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

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Any participant who has received prohibited systemic therapies, as per KY1005-CT05 (DRI17366) clinical trial protocol, either during or after completion of KY1005-CT05 (DRI17366) will not be eligible for the long-term extension (LTE)
- Participants who, during their participation in KY1005-CT05 (DRI17366), developed an adverse events (AE) or a serious adverse event (SAE) deemed related to amlitelimab, which in the opinion of the Investigator could indicate that continued treatment with amlitelimab may present an unreasonable risk for the participant
- Conditions in KY1005-CT05 (DRI17366), consistent with protocol-defined criteria for permanent IMP discontinuation, if deemed related to amlitelimab or led to Investigator or Sponsor-initiated withdrawal of participant from the study (e.g., non-compliance, inability to complete study assessments, etc.).
- Developed a medical condition that would preclude participation as per KY1005-CT05 (DRI17366) clinical trial protocol
- Concurrent participation in any other clinical study, including non-interventional studies
- Only in those participants entering after completion of KY1005-CT05 (DRI17366) safety follow-up
a) Newly diagnosed Tuberculosis (TB) or non-TB mycobacterial infections requiring treatment (including a positive QuantiFERON-TB Gold blood test at the screening visit),
b) Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody (HCV Ab) at the screening visit.
c) Laboratory values at the Screening Visit:
i) Serum creatinine > 1.6 mg/dL (141 micro mol/L) in female patients and > 1.9 mg/dL (168 micro mol/L) in male patients,
ii) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 x upper limit of normal (ULN),
iii) Serum total bilirubin >1.5 x ULN (except for subjects with Gilbert's syndrome, where total bilirubin must not exceed 3.0 mg/dL or 50 micro mol/L),
iv) In the Investigator's opinion, any additional clinically significant laboratory results from the clinical chemistry, haematology or urinalysis tests at the Screening visit.
d) In the Investigator's opinion any significant abnormality on 12-lead ECG at the screening visit.
- History of or known or suspected hypersensitivity to amlitelimab or the matching placebo formulation, or excipients used in the presentation of amlitelimab or placebo, or in preparation for administration. History of or known or suspected severe hypersensitivity reactions to other mAbs and/or their excipients.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05492578,2021-002344-73