Open label, long-term study evaluating safety and efficacy of subcutaneous amlitelimab in participants aged 12 years and older with moderate to severe atopic dermatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Research & Development

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

27 Sep 2023 → ongoing

Decision date (initial)

2023-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2022-502188-39-00

WHO UTN

U1111-1280-6080

ClinicalTrials.gov

NCT05769777

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacodynamic, Pharmacokinetic, Pharmacogenomic, Safety

To characterize the safety of long-term treatment with amlitelimab monotherapy administered by sub-cutaneous (SC) injection in participants with moderate-to-severe atopic dermatitis (AD)

Secondary objectives 3

1. Additional characterization of the safety of long-term treatment with amlitelimab monotherapy administered by SC injection in participants with moderate-to-severe AD
2. To characterize the efficacy of treatment with amlitelimab monotherapy administered by SC injection in participants with moderate-to-severe AD
3. To characterize the effect of amlitelimab on measures of Patient-Reported Outcomes (PROs) and quality of life (QoL)

Conditions and MedDRA coding

Dermatitis atopic

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant must be at least 12 years of age inclusive, at the time of signing the informed consent.
2. Participants must have AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer at baseline.
3. Participant must have documented history within 6 months prior to screening visit of inadequate response (including inadequate efficacy or medical inadvisability to topical treatments and/or inadequate response to systemic therapies (within 12 months prior to screening visit).
4. Eczema Area Severity Index (EASI) of 16 or higher at baseline visit/Visit 2.
5. Validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) of 3 or 4 at baseline visit/Visit 2.
6. AD involvement of 10% or more of body surface area (BSA) at baseline visit/Visit 2.
7. Weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) of ≥ 4 at baseline visit/Visit 2.
8. Able and willing to comply with requested study visits and procedures.
9. 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.
10. Body weight must be greater than or equal to 25 kg.

Exclusion criteria 15

1. Skin co-morbidity that would adversely affect the ability to undertake AD assessments as per investigator’s judgement.
2. 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.
3. 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 completely cured for more than 5 3 years prior to baseline).
4. History of solid organ or stem cell transplant.
5. 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.
6. Severe concomitant illness that would in the Investigator’s opinion inhibit the participant’s participation in the study.
7. 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.
8. 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); and any infection which as per Investigator’s opinion precludes the participant’s participation in the study.
9. 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
10. Having received any of the specified therapy within the specified timeframe(s) prior to the baseline visit.
11. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C at the screening visit.
12. Participants with active tuberculosis (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.
13. In the Investigator’s opinion, any clinically significant laboratory results from the clinical chemistry, hematology, coagulation, or urinalysis tests at the screening visit.
14. 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.
15. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs)
2. Percentage of participants who experienced Treatment-Emergent Serious Adverse Events (TESAEs)

Secondary endpoints 40

1. Percentage of participants who experienced Treatment-Emergent Adverse Events of Special Interest (AESI)
2. Percentage of participants with Potentially Clinically Significant Abnormalities (PCSA) for vital signs and clinical laboratory assessments, and electrocardiogram (ECG)
3. Percentage of participants discontinued from study treatment due to Adverse Events (AEs)
4. Percent change from baseline in Eczema Area and Severity Index (EASI) score
5. Proportion of participants with at least a 75% reduction from baseline in the EASI (EASI-75)
6. Proportion of participants with at least a 50% reduction from baseline in the EASI (EASI-50)
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
8. Change in percent Body Surface Area (BSA) affected by AD from baseline
9. Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline
10. Proportion of participants requiring rescue treatment at each visit
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
12. Percent change in weekly average of daily PP-NRS from baseline
13. Change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline
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
15. Change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline
16. 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
17. Change in Patient Oriented Eczema Measure (POEM) from baseline
18. Proportion of participants with a reduction in POEM ≥4 from Baseline in participants with POEM baseline ≥4
19. Change in Atopic Dermatitis Control Test (ADCT) from baseline
20. Proportion of participants with a reduction in ADCT ≥5 from baseline in participants with baseline ADCT≥7
21. Change in Dermatology Quality of Life Index (DLQI) from baseline in participants with age ≥16 years old
22. Proportion of participants with a reduction in DLQI ≥4 from Baseline in participants with age ≥16 years old and with DLQI at baseline ≥4
23. Change in Patient Global Impression of Severity (PGIS) from baseline
24. Proportions of participants who report symptoms to be “No” on the PGIS score
25. Proportions of participants who report symptoms to be “No” or “Mild” on the PGIS score
26. Proportion of participants who respond “Much better” on the Patient Global Impression of (PGIC) scale
27. Proportion of participants who respond “Much better” or “A little better” on the PGIC scale
28. Proportion of participants by PGIC responses
29. Change in Hospital Anxiety Depression Scale (HADS) from baseline
30. Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A ≥8
31. Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D Baseline ≥8
32. 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
33. Proportion of participants with vIGA-AD of 0
34. Proportion of participants with PP-NRS 0 or 1
35. Proportion of adolescent participants with a reduction in POEM ≥6 from Baseline in adolescents with POEM baseline ≥6
36. Change in Children’s Dermatology Life Quality Index (CDLQI) from baseline in participants with age ≥12 to <16 years old
37. Proportion of participants with age ≥12 to <16 with a reduction in CDLQI ≥4 from Baseline in participants with age ≥12 to <16 with CDLQI at baseline ≥6
38. Proportion of participants with age ≥12 to <16 with a reduction in CDLQI ≥6 from Baseline in participants with age ≥12 to <16 years old with CDLQI at baseline ≥6
39. Proportion of participants with at least a 90% reduction from baseline in the EASI (EASI-90)
40. Proportion of participants with at least 100% reduction from baseline in the EASI (EASI-100)

Investigational products

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

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Research & Development

Sponsor organisation

Sanofi-Aventis Research & Development

Address

1 Avenue Pierre Brossolette

City

Chilly Mazarin

Postcode

91380

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 17

Locations

8 EU/EEA countries · 49 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 266 files

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

Application history

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