Long-Term Safety and Efficacy evaluation of amlitelimab in participants of previous amlitelimab moderate to severe atopic dermatitis clinical trials

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Nov 2022 → ongoing

Decision date (initial)

2024-02-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2023-506548-18-00

EudraCT number

2021-002344-73

WHO UTN

U1111-1269-6490

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Efficacy, Pharmacodynamic

Characterize the safety of long-term treatment with amlitelimab in participants with atopic dermatitis (AD)

Secondary objectives 6

1. Additional characterization of safety of long-term treatment with amlitelimab in participants with AD
2. For participants entering the study from DRI17366 (STREAM-AD) Week 24: Characterize the efficacy of long-term treatment with amlitelimab in participants with AD
3. Characterize the pharmacokinetics profile of amlitelimab
4. Characterize the immunogenicity of long-term treatment with amlitelimab in participants with AD
5. Characterize the efficacy of long-term treatment with amlitelimab in participants with AD
6. Characterize the duration of efficacy of long-term treatment after withdrawal of amlitelimab in participants with AD

Conditions and MedDRA coding

Dermatitis atopic

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participant must be at least 12 years of age inclusive at the time of signing the informed consent.
2. 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 feederparent study SFY17915, INT18404, EFC17599, or EFC17600 --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 feederparent study, due to loss of clinical response in the part 2 of the feederparent 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 -- Participated in DRI17366 completing the previous study safety follow up (week 68) and wish to re-initiate treatment with amlitelimab up to one year after the last visit
3. Provide signed informed consent and able to comply with the requirements of the protocol
4. Complied with the previous clinical trial protocol to the satisfaction of the investigator
5. Body weight must be ≥25 kg

Exclusion criteria 12

1. Developed a medical condition that would preclude participation as described in the section for permanent discontinuation of the feeder study or LTS17367 protocol
2. Known history of or suspected current significant immunosuppression, including history of invasive opportunistic infections or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration
3. History of solid organ or stem cell transplant
4. 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)
5. Participants positive for human immunodeficiency virus (HIV); participants with any of the following results at Screening (Visit 1) or at any point during the feeder 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
6. History (within last 2 years prior to baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator
7. 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
8. Participants with an determinate or a confirmed positive IGRA test are excluded from the study unless all of the following conditions are met: a) 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 b) 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 c) For whom review and approval from Sponsor have been granted are eligible
9. Severe concomitant illness that would in the Investigator’s opinion inhibit the participant’s participation in the study, including for example, but not limited to, hypertension, renal disease, neurological conditions, heart failure and pulmonary disease
10. Skin co-morbidity that would adversely affect the ability to undertake AD assessments (e.g., psoriasis, tinea corporis, lupus erythematosus) as per Investigator’s judgment
11. Any medical condition which, in the opinion of the Investigator may present an unreasonable risk to the study participant as a result of his/her participation in this clinical study, may make particpant’s participation unreliable, or may interfere with study assessments
12. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of participants who experienced treatment-emergent adverse event (TEAE)

Secondary endpoints 29

1. Percentage of participants who experienced treatment-emergent serious adverse events (SAEs)
2. Percentage of participants who experienced treatment-emergent adverse events of special interest (AESI)
3. Absolute change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24
4. Percent change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24
5. Proportion of participants with EASI50/EASI75/EASI90 from DRI17366 baseline at each LTS17367 visit in participants entering the study from DRI17366 Week 24
6. Proportion of participants with a response of Validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) 0 or 1 at each LTS17367 visit in participants entering the study from DRI17366 Week 24
7. Absolute change from feeder study baseline in EASI score in all participants entering the study [each LTS17367 visit]
8. Percent change from feeder study baseline in EASI score in all participants entering the study [each LTS17367 visit]
9. Proportion of participants with EASI50/ EASI75/EASI90 in all participants entering the study [each LTS17367 visit]
10. Time to first EASI75/EASI90 in those participants who had not achieved it by the time of LTS17367 enrollment
11. Serum amlitelimab concentration assessed at prespecified time points through the end of the study
12. Number of participants with anti drug antibodies (ADAs) of amlitelimab at specified timepoints
13. Percentage of participants who experienced TEAE leading to treatment discontinuation
14. Proportion of participants with vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) at each LTS17367 visit
15. Proportion of participants requiring topical treatment in all participants entering the study [each LTS17367 visit]
16. Proportion of participants requiring rescue treatment [each LTS17367 visit]: all treatments in all participants entering the study
17. Time from enrollment in LTS17367 to first loss of vIGA-AD 0 in those participants who were vIGA-AD 0 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA)
18. Proportion of participants with vIGA-AD score 0/1 in all participants entering the study [each LTS17367 visit]
19. Proportion of participants with vIGA-AD score 0 [each LTS17367 visit]
20. Time to first vIGA-AD 0/1 after LTS17367 enrollment in those participants who had not achieved vIGA-AD 0/1 by the time of LTS17367 enrollment
21. Number of days on topical medication (per patient-year) in all participants entering the study
22. Change coming from feeder study baseline atopic dermatitis control tool (ADCT) in all participants entering the study [each LTS17367 visit]
23. Change from feeder study baseline in dermatology life quality index (DLQI/cDLQI) in all participants entering the study [each LTS17367 visit]
24. Change from feeder study baseline^ in patient oriented eczema measure (POEM) in all participants entering the study [each LTS17367 visit]
25. Change from feeder study baseline in BSA-AD [each LTS17367 visit]
26. Time from enrollment in LTS17367 to first loss EASI75 in those participants who had reached EASI75 at LTS17367 rollover coming from EFC17600 (ESTUARY) and EFC17599 (AQUA)
27. Time from enrollment in LTS17367 to first loss of vIGA-AD 0/1 in those participants who were vIGA-AD 0/1 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA)
28. Time from LTS17367 baseline to re-treatment with amlitelimab in those participants who were vIGA-AD 0/1 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA).
29. Time from last amlitelimab dose in feeder study to re-treatment with amlitelimab in those participants who were vIGA-AD 0/1 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 22

Locations

13 EU/EEA countries · 128 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 139 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

25 submissions — initial application plus substantial / non-substantial modifications