Efficacy and Safety of Methotrexate Versus Placebo in Adults With Atopic Dermatitis.
Topic / Pathology
- interventional
Objectives
Phase 3, randomized, two-arm, parallel-group, double-blind, placebo-controlled trial to assess the efficacy and safety of subcutaneous methotrexate versus placebo in moderate-to-severe atopic dermatitis.
To demonstrate the superiority of subcutaneous (SC) methotrexate (MTX) versus placebo in improving from baseline at least 75% of the EASI score (i.e., achieving an EASI 75 response) at the Week 16 visit of the trial in adult participants with moderate-to-severe atopic dermatitis (AD).
The maximum duration of participation in the trial for each participant is 37 weeks, with a maximum screening period of 4 weeks, 16 weeks of treatment and, for participants with an EASI 50 response at the week 16 visit, a further 8 weeks of blinded treatment (blinded extension phase) and 9 weeks of follow-up at the end of the treatment extension. Participants failing to achieve an EASI 50 response at the week 16 visit will discontinue treatment at the week 16 visit, and their participation will cease after the week 20 visit.
During the treatment phase, participants will receive weekly doses of MTX or placebo SC for 16 weeks. Participants with an EASI 50 response at the Week 16 visit will also receive weekly doses of MTX or placebo SC for a further 8 weeks (blinded extension phase).
https://clinicaltrials.gov/study/NCT06239311?term=NCT06239311&rank=1
Sponsor
medac GmbH
Investigator
Pr Audrey Nosbaum
Critères d'inclusion
- Effective contraception for the duration of the study and for 6 months after the last trial treatment.
- Diagnosis of atopic dermatitis (AD) at least 12 months prior to the selection visit, according to Hanifin and Rajka criteria for AD.
- Moderate to severe atopic dermatitis, defined by the following criteria at baseline visit EASI ≥ 16, IGA ≥ 3, DLQI ≥ 10.
- Eligible for systemic therapy, i.e., documented history (within 12 months prior to baseline visit) of inadequate response to topical corticosteroid (TCC) or topical calcineurin inhibitor (TCI) therapy or documented systemic therapy for AD (such as cyclosporine (CYC), azathioprine and/or mycophenolate mofetil).
- Inadequate response to TBS or ITC is defined as failure to achieve or maintain remission or low-grade disease (IGA ≥ 2) despite daily treatment with a class 2 or class 3 TBS or ITC for 28 days (or the maximum duration allowed according to the SPC.
- Treated with a stable dose of topical emollient for at least 7 consecutive days prior to baseline visit.
- Chest X-ray with no clinically relevant abnormalities within the last 6 months prior to the index visit.
Critères de non-inclusion
- Previous treatment with MTX
- with known hypersensitivity to MTX or folic acid or to any of the excipients with known oral ulcers and active gastrointestinal ulcer disease
- with known blood dyscrasias
- Liver impairment and/or aspartate transaminase (AST) or alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN), or bilirubin > 5 mg/dL (85.5 μmol/L), or positive FibrotestTM result at screening visit.
- Renal insufficiency (creatinine clearance less than 60 ml/min)
- Severe acute or chronic infections, such as tuberculosis, hepatitis B or C, seropositivity or other immunodeficiency syndromes.
- Presenting an uncontrolled infection,
- Have a history of malignant tumors
- Suffering from or having a history of other concomitant skin conditions that could interfere with the assessment of AD (e.g. psoriasis, lupus erythematosus, eczema herpeticum)
- Treatment with an investigational drug within 8 weeks or 5 half-lives (if known), whichever is longer, prior to baseline.
- Treatment with TCS, calcineurin inhibitors or phosphodiesterase-4 inhibitors such as crisaborole within one week prior to baseline.
- Other exclusion criteria include previous treatments
Status
Ongoing
