A study to evaluate the efficacy and safety of subcutaneous amlitelimab monotherapy compared with placebo 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

29 May 2024 → 13 Nov 2025

Decision date (initial)

2024-05-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2022-501196-41-00

WHO UTN

U1111-1275-9715

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Pharmacodynamic, Safety

To demonstrate the efficacy of amlitelimab monotherapy in comparison to placebo in participants aged 12 years and older with moderate-to-severe atopic dermatitis (AD)

Secondary objectives 4

1. To assess the efficacy of amlitelimab monotherapy in comparison to placebo in participants aged 12 years and older with moderate-to-severe AD
2. To assess the safety profile of amlitelimab monotherapy in participants aged 12 years and older with moderate-to-severe AD
3. To characterize the pharmacokinetic profile of amlitelimab monotherapy in participants aged 12 years and older with moderate-to-severe AD
4. To characterize immunogenicity of amlitelimab monotherapy in participants aged 12 years and older with moderate-to-severe AD

Conditions and MedDRA coding

Dermatitis atopic

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 9

1. Participants must be 12 years of age (when signing informed consent form)
2. Diagnosis of AD for at least 1 year (defined by the American Academy of Dermatology Consensus Criteria)
3. Documented history (within 6 months before screening) of either inadequate response or inadvisability to topical treatments, and/or inadequate response to systemic therapies (within 12 months before screening)
4. v-IGA-AD of 3 or 4 at baseline visit
5. EASI score of 16 or higher at baseline
6. AD involvement of 10% or more of BSA at baseline
7. Weekly average of daily PP-NRS of ≥ 4 at baseline visit.
8. Able and willing to comply with requested study visits and procedures
9. Body weight ≥25 kg

Exclusion criteria 10

1. Skin co-morbidity that would adversely affect the ability to undertake AD assessments
2. Known history of or suspected significant current immunosuppression
3. Any malignancies or history of malignancies prior to baseline (with the exception of non-melanoma skin cancer excised and cured >5 years prior to baseline)
4. History of solid organ or stem cell transplant
5. Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior to baseline (1 week in the event of superficial skin infections)
6. Positive for human immunodeficiency virus (HIV), Hepatitis B or hepatitis C at screening visit
7. Having active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection, or who are at high risk of contracting TB
8. Having received any of the specified therapy within the specified timeframe(s) prior to the baseline visit
9. In the Investigator’s opinion, any clinically significant laboratory results or protocol specified laboratory abnormalities at screening
10. History of hypersensitivity or allergy to any of the excipients or investigational medicinal product (IMP)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. EU, EU reference countries, and Japan: Proportion of participants with Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points at Week 24
2. EU, EU reference countries, and Japan: Proportion of participants reaching 75% reduction from baseline in Eczema Area and Severity Index (EASI) score (EASI-75) at Week 24
3. US and US reference countries: Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points at Week 24

Secondary endpoints 37

1. Proportion of participants reaching EASI-75 at Week 24 (for US and US reference countries only)
2. Proportion of participants with vIGA-AD 0 (clear) or 1 (almost clear) with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) and a reduction from baseline of ≥2 points
3. 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
4. Proportion of participants reaching EASI-75
5. Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points
6. Proportion of participants reaching EASI-90
7. Proportion of participants reaching EASI-100
8. Proportion of participants with PP-NRS 0 or 1
9. Change in Dermatology Life Quality Index (DLQI) from baseline in participants with age ≥16 years old
10. Proportion of participants with a reduction in DLQI ≥4 from baseline in participants with age ≥16 years old and with DLQI baseline ≥4
11. Change in Children Dermatology Life Quality Index (CDLQI) from baseline in participants with age ≥12 to <16 years old
12. Proportion of participants with a reduction in CDLQI ≥6 from baseline in participants with age ≥12 to <16 years old and with CDLQI baseline ≥6
13. Change in Hospital Anxiety Depression Scale (HADS) from baseline
14. Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A ≥8
15. Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D baseline ≥8
16. Absolute change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline
17. 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
18. Absolute change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline
19. Proportion of participants with a reduction in weekly average of daily SD-NRS ≥3 from baseline in participants with Baseline weekly average of daily SD-NRS ≥3
20. Percent change in EASI score from baseline
21. Percent change in weekly average of daily PP-NRS from baseline
22. Absolute change in weekly average of daily PP-NRS from baseline
23. Proportion of participants reaching EASI-50
24. Proportion of participants with EASI ≤7
25. Change in percent Body Surface Area (BSA) affected by AD from baseline
26. Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline
27. Absolute change in Scoring Atopic Dermatitis (SCORAD) index from baseline
28. Proportion of participants with a reduction in SCORAD ≥ 8.7 points from baseline in participants with baseline SCORAD score ≥ 8.7
29. Change in Patient Oriented Eczema Measure (POEM) from baseline
30. Proportion of participants with a reduction in POEM ≥4 from baseline in participants with POEM Baseline ≥4
31. Proportion of participants with rescue medication use
32. Percentage of participants who experience Treatment-Emergent Adverse Events (TEAEs), experience Treatment-Emergent Serious Adverse Events (TESAEs) and/or Treatment- Emergent Adverse Events of Special Interest (AESI)
33. Serum amlitelimab concentrations
34. Incidence of antidrug antibodies (ADAs) of amlitelimab
35. Percent change in weekly average of daily SP-NRS from baseline
36. Proportion of participants with vIGA-AD 0
37. Percent change in weekly average of daily SD-NRS

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 Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 15

Locations

4 EU/EEA countries · 28 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 125 files

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

Application history

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