Evaluation of Long-Term Safety, Tolerability, and Efficacy of Subcutaneous Amlitelimab in Patients with Moderate to Severe Atopic Dermatitis from Previous Trials
- Trial ID
- 2023-506548-18-00
- Protocol
- LTS17367
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to **characterize the safety** of long-term treatment with amlitelimab in participants with moderate to severe **atopic dermatitis** (AD). This is clinically relevant as it aims to ensure that prolonged use of amlitelimab does not result in adverse effects, thereby supporting its potential as a sustainable therapeutic option for managing AD.
Secondary objectives include:
- Additional characterization of the safety of long-term treatment with amlitelimab in participants with AD.
- Characterize the efficacy of long-term treatment with amlitelimab in participants with AD.
- Characterize the pharmacokinetics profile of amlitelimab.
- Characterize the pharmacodynamic profile of amlitelimab.
These secondary objectives are crucial for understanding the comprehensive impact of amlitelimab, including its effectiveness, how it is processed in the body, and its biological effects, which are essential for optimizing treatment regimens and improving patient outcomes in AD management.
Participants
The clinical trial involves a total of **961 participants** diagnosed with **atopic dermatitis**. The study population includes both male and female subjects, with an age range starting from 12 years and above. Participants were selected based on their previous involvement in an amlitelimab clinical trial for moderate to severe atopic dermatitis, having completed the necessary assessments and reached specific timepoints in their respective studies. The trial includes individuals who have demonstrated compliance with prior clinical trial protocols and have a body weight of at least 25 kg. The population is characterized by a mix of age groups and includes a vulnerable population. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the long-term safety, tolerability, and efficacy of **amlitelimab** in participants with moderate to severe atopic dermatitis. This study is a long-term extension of previous trials involving amlitelimab and follows a randomized, double-blind, controlled design. The trial is expected to commence on November 10, 2023, and conclude by December 29, 2028, with a maximum treatment period of 316 days for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, previous participation in amlitelimab trials, and compliance with prior protocols. The primary objective is to characterize the safety of long-term treatment, with the primary endpoint being the percentage of participants experiencing treatment-emergent adverse events (TEAEs). Secondary endpoints include the percentage of participants with serious adverse events (SAEs) and adverse events of special interest (AESIs), as well as changes in the Eczema Area and Skin Severity Index (EASI) scores.
Study visits will occur at pre-specified intervals to monitor safety and efficacy, with assessments including EASI scores, validated investigator global assessment scale for atopic dermatitis (vIGA-AD), and serum amlitelimab concentrations. The end-of-study visit will finalize data collection and assess the overall outcomes of the trial. Participant involvement is expected to last up to 316 days, with conditions for early termination including non-compliance with study protocols or the occurrence of significant adverse events.
Treatment
The clinical trial involves the administration of **Amlitelimab**, a novel human anti-OX40L monoclonal antibody, as the experimental medication. Amlitelimab is provided in the form of a **solution for injection** and is administered via **subcutaneous injection**. The maximum daily dose is 250 mg, with a total maximum dose of 19,500 mg over a treatment period of up to 316 days. The pharmaceutical formulation is not designed for pediatric use, and the medication is not classified as an orphan drug. The active substance, amlitelimab, is a protein of other origin, developed by Sanofi Aventis Recherche et Développement (SAR).
In addition to the experimental treatment, the study includes the use of non-experimental treatments categorized under the **ATC** codes H02AB, D07A, and D11AH. These treatments are auxiliary and include glucocorticoids, corticosteroids (plain), and agents for dermatitis excluding corticosteroids, respectively. The glucocorticoids are administered orally, while the corticosteroids and dermatitis agents are applied topically. The pharmaceutical forms of these auxiliary treatments are not specified due to the diversity of the ATC level selected, and they are not intended for pediatric use. The maximum treatment period for these auxiliary treatments is one day, with no specified maximum daily or total dose amounts.
Efficacy
The efficacy of the clinical trial evaluating **amlitelimab** in participants with moderate to severe atopic dermatitis will be assessed through a series of predefined secondary endpoints. These endpoints include the absolute and percent change from baseline in the Eczema Area and Severity Index (EASI) score at each visit for participants entering the study from a previous trial. Additionally, the proportion of participants achieving EASI75, EASI90, and EASI100 will be measured at specified timepoints. The validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) will also be utilized to determine the proportion of participants achieving a score of 0 or 1, indicating clear or almost clear skin, at each visit.
Further efficacy assessments will involve the time to first achievement of EASI75, EASI90, and EASI100, as well as the time to first remission, defined as achieving a vIGA-AD score of 0 or 1. The study will also evaluate the proportion of participants requiring rescue treatment and the number of days on topical medication per patient-year. Patient-reported outcomes will be collected using the Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) at prespecified timepoints. Serum concentrations of **amlitelimab** and the presence of anti-drug antibodies (ADAs) will be assessed to further understand the treatment's efficacy and immunogenicity.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be at least 12 years of age inclusive at the time of signing the informed consent.
- 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
- Provide signed informed consent and able to comply with the requirements of the protocol
- Complied with the previous clinical trial protocol to the satisfaction of the investigator
- Body weight must be ≥25 kg
Exclusion Criteria
- Developed a medical condition that would preclude participation as described in the section for permanent discontinuation of the feeder study or LTS17367 protocol
- 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
- History of solid organ or stem cell transplant
- 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)
- 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
- History (within last 2 years prior to baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator
- 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
- 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
- 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
- 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
- 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
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 10 Nov 2022 | 71 |
 Czechia | Recruiting | 10 Nov 2022 | 75 |
 Denmark | Recruiting | 10 Nov 2022 | 5 |
 France | Recruiting | 10 Nov 2022 | 24 |
 Germany | Not Recruiting | 10 Nov 2022 | 64 |
 Greece | Recruiting | 10 Nov 2022 | 9 |
 Hungary | Recruiting | 10 Nov 2022 | 4 |
 Italy | Recruiting | 10 Nov 2022 | 18 |
 The Netherlands | Not Recruiting | 10 Nov 2022 | — |
 Poland | Recruiting | 10 Nov 2022 | 147 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Amlitelimab | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 250 | 316 | PRD10317943 |
Amlitelimab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 250 | 316 | PRD10309623 |
- | Other | PHF00017MIG | TOPICAL | 0 | 1 | D07A |
- | Other | PHF00231MIG | ORAL | 0 | 1 | H02AB |
- | Other | PHF00103MIG | TOPICAL | 0 | 1 | D11AH |
Amlitelimab | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 125 | 196 | PRD11083348 |