A study to evaluate the treatment response and safety of two dose regimens of subcutaneous amlitelimab compared with treatment withdrawal in participants aged 12 years and older with moderate-to severe atopic dermatitis

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] - Skin and Connective Tissue Diseases [C17]

Trial duration

30 Oct 2024 → ongoing

Decision date (initial)

2024-07-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2023-508096-36-00

WHO UTN

U1111-1290-9215

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy

{US & US countries} To assess maintenance of treatment response to amlitelimab monotherapy Q12W compared to treatment withdrawal in responders with moderate-to-severe AD from monotherapy parent studies
{EU & EU countries} To assess maintenance of treatment response to amlitelimab monotherapy Q12W compared to treatment withdrawal in responders with moderate-to-severe AD

Secondary objectives 10

1. To assess the maintenance of treatment response to amlitelimab monotherapy compared to treatment withdrawal in responders with moderate-to-severe AD
2. To characterize the treatment response to amlitelimab in non-responders with moderate-to-severe AD
3. To assess the safety profile of amlitelimab monotherapy as maintenance therapy in participants with moderate-to-severe AD
4. To assess the pharmacokinetic (PK) profile of amlitelimab monotherapy as maintenance therapy in participants with moderate-to-severe AD
5. To assess immunogenicity of amlitelimab monotherapy as maintenance therapy in participants with moderate-to-severe AD
6. To assess duration of maintained response to amlitelimab in responders with moderate-to-severe AD
7. To assess recapture of treatment response to amlitelimab among participants who meet the pre-defined relapse criteria.
8. To characterize the treatment response to amlitelimab up to Week 72, including the 24-week induction period
9. To characterize Q12W maintenance of response through Week 72, including the 24-week induction period.
10. To evaluate the response of amlitelimab on Head & Neck EASI sub-scores in participants with head and neck atopic dermatitis at parent study baseline

Conditions and MedDRA coding

atopic dermatitis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003233-PIP01-22

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participants must be at least 12 years of age inclusive, at the time the informed consent is signed.
2. Must have participated, received study treatment without permanent investigational medicinal product (IMP) discontinuation, and adequately completed the assessments required for the treatment period in one of the three 24-week parent studies EFC17559 (COAST-1), EFC17560 (COAST-2) or EFC17561 (SHORE) for moderate- to-severe AD.
3. Able and willing to comply with requested study visit and procedures.
4. Body weight must be ≥ 25 kg.

Exclusion criteria 6

1. Developed a medical condition that would preclude participation as described in Exclusion Criteria or Permanent Discontinuation of EFC17559 (COAST-1)/EFC17560 (COAST- 2)/EFC17561 (SHORE) clinical trial protocols.
2. Having received any prohibited medication or procedure for AD that resulted in IMP discontinuation in the parent study EFC17559 (COAST-1), EFC17560 (COAST-2) or EFC17561 (SHORE).
3. Participants who, during their participation in the parent study EFC17559 (COAST-1) /EFC17560 (COAST-2)/EFC17561 (SHORE), developed an AE or a 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.
4. Participants who have had IMP permanently discontinued for any reason before or at the time of the planned first dose in the EFC17600 (ESTUARY) study.
5. Conditions in the parent study EFC17559 (COAST-1)/EFC17560 (COAST- 2)/EFC17561 (SHORE) that led to Investigator - or Sponsor-initiated withdrawal of participant from the study (eg, non-compliance, inability to complete study assessments, etc.).
6. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1-{US and US countries} Proportion of participants who are responders AND maintained vIGA-AD ≤2 without experiencing relapse among participants who were responders at baseline of ESTUARY.
2. 2-{EU & EU countries} Proportion of participants who maintain treatment response in ESTUARY without experiencing relapse.

Secondary endpoints 48

1. 1-Proportion of participants who continue to be EASI-75^ among the participants who met EASI-75^ at baseline of ESTUARY. The symbol ^ represents "based on parent study baseline”.
2. 2-Proportion of participants who continue to be vIGA-AD 0 or 1 among participants who met vIGA-AD 0 or 1 at baseline of ESTUARY
3. 3-Proportion of participants who continue to be vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) among the participants who are vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) at baseline of ESTUARY
4. 4-Proportion of participants who maintained weekly average of daily PP-NRS reduction of ≥4^ among the participants with weekly average of daily PP-NRS reduction of ≥ 4^ at baseline of ESTUARY.
5. 5-Proportion of participants who maintain treatment response without experiencing relapse
6. 6-Percent change in EASI from parent study baseline
7. 7-Proportion of participants who maintained EASI-75^ without experiencing relapse among the participants who met EASI-75^ at baseline of ESTUARY
8. 8-Proportion of participants with EASI-75^
9. 9-Proportion of participants who continue to be EASI-90^ among the participants who met EASI-90^ at baseline of ESTUARY
10. 10-Proportion of participants with EASI-90^
11. 11-Time to the first event of vIGA-AD ≥3 or loss of EASI-75^ among the participants who were vIGA-AD 0 or EASI-75^ at baseline of ESTUARY
12. 12-Proportion of participants with vIGA-AD 0 or 1
13. 13-Proportion of participants who are vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting)
14. 14-EU countries:Time to first event of vIGA-AD ≥3 or loss of EASI^75 among those participants who were vIGA-AD 0 or 1 at baseline of ESTUARY
15. 15-EU countries: Time to first event of vIGA-AD ≥3or loss of EASI^75 among those participants who were vIGA-AD 0 at baseline of ESTUARY
16. 16-Proportion of participants with weekly average of daily PP-NRS reduction of ≥4^
17. 17-Proportion of participants who maintain PP-NRS ≤4 among participants who were PP-NRS ≤4 at baseline of ESTUARY
18. 18-EU countries: Proportion of participants who maintained reduction in POEM ≥4^ among the participants with reduction in POEM ≥4^ at baseline of ESTUARY
19. 19-EU countries: Proportion of participants with a reduction in CDLQI ≥6^ among participants aged ≥12 to <16 years old and with reduction in CDLQI ≥6^ at baseline of ESTUARY
20. 20-EU countries: Proportion of participants with reduction in DLQI ≥4^ among the participants aged ≥16 years old and with reduction in DLQI ≥4^ at baseline of ESTUARY
21. 21-Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and/or Treatment-Emergent Adverse Events of Special Interest (AESI)
22. 22-Pharmacokinetic serum amlitelimab concentrations
23. 23-Incidence of antidrug antibodies (ADAs) of amlitelimab
24. 24A-Pharmacokinetic: maximum plasma concentration (Cmax)
25. 24B-Pharmacokinetic: AUC4W and AUC12W
26. 25-Proportion of participants who are EASI-75^ among participants who had EASI-75^ at baseline of ESTUARY and did not relapse by Week 12
27. 26-Time to first recapture of EASI-75^ among participants who had EASI-75^ at baseline of ESTUARY and subsequently relapsed
28. 27-Proportion of participants who recapture EASI-75^ by visit among the patients who had EASI-75^ at baseline of ESTUARY and subsequently relapsed
29. 28-Proportion of participants who are EASI 90^ AND who maintain EASI-75^ without experiencing relapse among participants who had EASI-90^ at baseline of ESTUARY
30. 29-Proportion of participants who are EASI 90^ without experiencing relapse among participants who had EASI-90^ at baseline of ESTUARY
31. 30-Proportion of participants who are EASI-90^ among participants who had EASI-90^ at baseline of ESTUARY and did not relapse by Week 12.
32. 31-Proportion of participants who are vIGA-AD 0 or 1 AND who maintain vIGA-AD ≤2 without experiencing relapse among participants who had vIGA-AD 0 or 1 at baseline of ESTUARY
33. 32-Proportion of participants who maintain vIGA-AD response within 1 point of baseline without experiencing relapse among participants who had vIGA-AD 0 or 1 at baseline of ESTUARY
34. 33-Proportion of participants who maintain vIGA-AD 0 or 1 without experiencing relapse among participants who had vIGA-AD 0 or 1 at baseline of ESTUARY
35. 34-Proportion of participants who are vIGA-AD 0 or 1 without experiencing relapse among participants who had vIGA-AD 0 or 1 at baseline of ESTUARY
36. 35-Time to first recapture of vIGA-AD 0 or 1 among participants who had vIGA-AD 0 or 1 at baseline of ESTUARY and subsequently relapsed
37. 36-Proportion of participants who recapture vIGA-AD 0 or 1 among participants who had vIGA-AD 0 or 1 at baseline of ESTUARY and subsequently relapsed
38. 37-Proportion of participants who are vIGA-AD 0 or 1 among participants who had vIGA-AD 0 or 1 at baseline of ESTUARY and did not relapse by Week 12.
39. 38-Proportion of participants who are vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) AND who maintain vIGA-AD ≤2 without experiencing relapse among participants who had vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) at baseline of ESTUARY
40. 39-Proportion of participants who are vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) among participants who had vIGA-AD 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) at baseline of ESTUARY and did not relapse by Week 12
41. 40-Proportion of participants who maintain weekly average of daily PP-NRS reduction of ≥4^ without experiencing relapse among participants with weekly average of daily PP NRS reduction of ≥4^ at baseline of ESTUARY
42. 41-Proportion of participants who maintain PP NRS ≤4 without experiencing relapse among participants who had PP-NRS ≤4 at baseline of ESTUARY
43. 42-Proportion of participants who achieve PP-NRS reduction of ≥4
44. 43-Proportion of participants who achieve PP-NRS ≤4
45. 44-Duration of maintained response without relapse (remittive effect) (Time to last observed maintained response without relapse
46. 45-Percent change in Head & Neck EASI sub-score from the parent study baseline among participants with Head & Neck EASI sub-score >0 at baseline of the parent study
47. 46-Proportion of participants Head & Neck EASI sub-score EASI-75^ among participants with Head & Neck EASI sub-score >0 at baseline of the parent study
48. 47-Proportion of participants with Head & Neck EASI sub-score EASI-90^ among participants with Head & Neck EASI sub-score >0 at baseline of parent study

Investigational products

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

Test 2

Placebo 1

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 Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 8

Locations

11 EU/EEA countries · 82 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 158 files

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

Application history

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