Efficacy and Safety of Methotrexate versus Placebo in Adults with Atopic Dermatitis

Phase 1

Recruiting

Conditions: moderate to severe atopic dermatitis
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: CTIS2023-504443-13-00

Lead Sponsor: Medac Gesellschaft fuer klinische Spezialprapaerate mbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 212

Inclusion Criteria

Male or female adult (ie, aged 18 years or older), Covered by health care insurance in accordance with local requirements, Woman of childbearing potential must have a negative pregnancy test at the Screening Visit and must agree to use highly effective methods of contraception while taking the IMP and for 6 months after the last IMP administration. Men must agree to use a condom during intercourse while taking the IMP and for 3 months after the last IMP administration. They must also agree to not donate sperm for the time period starting at the Screening Visit, throughout the entire trial period, and for at least 3 months after the last IMP administration., Diagnosis of AD at least 12 months prior to the Screening Visit, diagnosed as defined by the Hanifin and Rajka criteria for AD, Moderate to severe AD, defined as the following criteria at the Baseline Visit: EASI = 16, IGA = 3, DLQI = 10, Eligible for systemic treatment, ie, documented history (within 12 months prior to Baseline Visit) of inadequate response to treatment with TCS or TCIs or documented systemic treatment for AD (such as CYC, azathioprine and/or mycophenolate mofetil). Inadequate response to TCS or TCI is defined as failure to obtain or maintain a remission or a low activity disease (IGA = 2) despite a daily treatment with a class 2 or class 3 TCS or TCI for 28 days (or the maximal authorised duration according to the SmPC), Treated with a stable dose of topical emollient, for at least 7 consecutive days prior to the Baseline Visit, Chest X-ray without clinically relevant abnormalities performed within the last 6 months prior to the Baseline Visit, Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, Willing and able to comply with the protocol requirements for the duration of the trial

Exclusion Criteria

Pregnant or breast-feeding women, or planning to become pregnant, or to breastfeed during the trial, Presenting uncontrolled infection, hospitalisation due to uncontrolled infection or treatment with intravenous antibiotics for infection within 2 months prior to the Baseline Visit, Presenting a history of malignancy, including solid tumours and haematologic malignancies, except non-melanoma skin cancer (epithelial cell carcinoma or basal cell carcinoma) and cervical carcinoma in situ that have been treated with no evidence of recurrence during the past 5 years, Currently experiencing or having a history of other concomitant skin conditions that would interfere with evaluation of AD (eg. psoriasis, lupus erythematosus, eczema herpeticum), Treated with an investigational drug within 8 weeks or within 5 half-lifes (if known), whichever is longer, before the Baseline Visit, Treated with TCS, calcineurin inhibitors or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the Baseline Visit, Treated with oral corticosteroids, azathioprine, mycophenolate mofetil, CYC or any other systemic immunosuppressor / immunomodulator within 4 weeks before the Baseline Visit, Treated by specific allergen immunotherapy started within 3 months before the Baseline Visit, Treated with a monoclonal antibody (including but not limited to dupilumab or tralokinumab) within the last 3 months or 5 times the half-life of the respective monoclonal antibody (whichever is the longer period) or with any JAK inhibitors (including but not limited to ruxolitinib, baricitinib, tofacitinib, upadicitinib, or abrocitinib) within the last 4 weeks prior to the Baseline Visit, Treated with any parenteral corticosteroid within 6 weeks prior to the Baseline Visit, Treated with ultraviolet therapy within 4 weeks prior to the Baseline Visit, Previously treated with MTX, Received a live (attenuated) vaccine within 4 weeks before the Baseline Visit or planning to be vaccinated with live vaccine during the trial, Having a planned surgery during the trial, Presenting a clinically significant medical disease that is uncontrolled despite treatment that, in the opinion of the Investigator, is likely to impact the ability to participate in the trial or to impact the trial efficacy or safety assessments, Presenting any additional condition that, in the opinion of the Investigator, may interfere with the assessment or may put the participant at risk, Protected by the law (adult under guardianship, or hospitalised in a public or private institution for a reason other than this trial, or incarcerated), Persons performing mandatory military service, persons deprived of liberty, persons who, due to a judicial decision, cannot take part in clinical trials, and persons, who due to their age, disability or state of health are reliant on care and for that reason accommodated in residential care institutions, that is accommodations providing an uninterrupted assistance for persons who necessitate such assistance, are in a situation of subordination or factual dependency and therefore may require specific protective measures, Presenting a known hypersensitivity to MTX or folic acid as well as to any of the excipients, Presenting ulcers of the oral cavity and known active gastrointestinal ulcer disease, Presenting with known blood dyscrasia (haemoglobin < 8.0 g/dL or white blood cell count < 4000/mm3 or platelet count < 100000/mm3), Presenting liver impairment and/or AST or ALT > 2 ti

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the superiority of subcutaneous (SC) methotrexate (MTX) versus placebo with respect to an improvement from baseline of at least 75% of the Eczema Area and Severity Index (EASI 75 response) at the Trial Week 16 Visit in adult participants with moderate to severe atopic dermatitis (AD);Secondary Objective: To compare the efficacy of MTX (SC) versus placebo at different defined timepoints in participants with moderate to severe AD, To compare the safety and tolerability profiles of MTX (SC) versus placebo in participants with moderate to severe AD, To compare the quality of life of participants treated with MTX (SC) versus placebo at different defined timepoints in participants with moderate to severe AD, To evaluate the maintenance of the efficacy of MTX versus placebo in participants during the extension phase;Primary end point(s): EASI 75 response at the Trial Week 16 Visit

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):EASI, SCORAD, IGA, NRS and POEM scores or responses at different time points including Trial Week 4, Trial Week 8, Trial Week 12 and Trial Week 16;Secondary end point(s):Adverse events (AE), treatment-related AEs, serious adverse events (SAEs) occurring from the Screening Visit until the Trial Week 16/24 Visit, and serious adverse reactions (SARs) occurring from start of the trial intervention until Trial Week 20/33 Visit - time points depending on participation in the extension phase or not. Change in vital signs and laboratory values.;Secondary end point(s):Change in DLQI, SCORAD, WPAI:GH, HADS, EQ-5D-5L and ADCT scores or responses from baseline to different time points including Trial Week 4, Trial Week 8, Trial Week 12, and Trial Week 16;Secondary end point(s):EASI, IGA, NRS, SCORAD, DLQI, WPAI:GH, HADS, EQ-5D-5L and ADCT responses at Trial Week 24 or change in scores or responses between Trial Week 16 and Trial Week 24