Efficacy and Safety of Methotrexate Versus Placebo in Adults With Atopic Dermatitis.

NCT06239311 | Recruiting Phase 3

• 2 other identifiers: MC-MTX.18/AD2023-504443-13-00
• Study Type: interventional
• Target: 277
• Locations: 4 countries
• Sites: 30

Brief Summary

Atopic dermatitis is an ongoing condition that causes skin irritation, redness, and itchiness. Treatments are usually topical - applied to the skin (e.g., moisturisers or medicated creams) - but a wider variety of systemic treatments (that target the whole body) are needed for those whose condition does not improve with topical treatments. Methotrexate, a drug approved for similar conditions such as arthritis and psoriasis, has been shown to improve atopic dermatitis. This randomised, controlled clinical trial will investigate how effective.

Conditions

Moderate to Severe Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

• Eczema Area and Severity Index (EASI) 75 response at Trial Week 16 Visit

  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). The Eczema Area and Severity Index (EASI) is an investigator-assessed instrument for measuring the severity of clinical symptoms in atopic dermatitis (AD). The minimum EASI score is 0 (= normal) and the maximum EASI score is 72 (= very severe).

  Trial Week 16

Secondary Outcomes (22)

• Improvement from baseline of at least 50% in the Eczema Area and Severity Index (EASI 50 response)

  Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16

• Improvement from baseline of at least 75% in the Eczema Area and Severity Index (EASI 75 response)

  Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 24

• Improvement from baseline of at least 90% in the Eczema Area and Severity Index (EASI 90 response)

  Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16

• Change from baseline in the Eczema Area and Severity Index (EASI) score.

  Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16

• Scoring Atopic Dermatitis (SCORAD) 50 response

  Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16

Study Arms (2)

Methotrexate

ACTIVE COMPARATOR

Participants will receive 16 to 24 weekly subcutaneous injections of 20 mg . In case of intolerance of the 20 mg dose, a reduction to 15 mg per week is possible.

Drug: Methotrexate

Placebo

PLACEBO COMPARATOR

Participants will receive 16 to 24 weekly subcutaneous injections

Drug: Placebo

Interventions

Methotrexate DRUG

Solution for injection in prefilled pen

Methotrexate

Placebo DRUG

Solution for injection in prefilled pen

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 investigational medicinal product (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 atopic dermatitis (AD) at least 12 months prior to the Screening Visit, diagnosed as defined by the Hanifin and Rajka criteria for AD 4.
• Moderate to severe AD, defined as the following criteria at the Baseline Visit: Eczema Area and Severity Index (EASI) ≥ 16, Investigator Global Assessment (IGA) ≥ 3, Dermatology Life Quality Index (DLQI) ≥ 10
• Eligible for systemic treatment, ie, documented history (within 12 months prior to Baseline Visit) of inadequate response to treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI)s or documented systemic treatment for AD (such as cyclosporine (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 Summary of Product Characteristics (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
• Covered by health care insurance in accordance with local requirements

You may not qualify if:

• Pregnant or breast-feeding women, or planning to become pregnant, or to breastfeed during the trial
• Previously treated with MTX
• 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 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 a positive result in the FibrotestTM at the Screening Visit
• Presenting drug or alcohol abuse within the last 12 months
• Presenting renal impairment (creatinine clearance less than 60 mL/min)
• Presenting serious, acute or chronic infections such as tuberculosis, hepatitis B or C, HIV positive, or other immunodeficiency syndromes
• A positive test result at Screening for hepatitis B surface antigen (HBsAg) and/or core antibodies (anti-HBc) excludes the patient from trial participation. Patients with positive surface antibodies (anti-HBs) and a history of hepatitis B virus (HBV) vaccination may be included.
• A positive test result at Screening for hepatitis C (positive hepatitis C virus (HCV) antibody test confirmed with positive hepatitis C RNA test) excludes the patient from trial participation, even if they have received appropriate and effective treatment, due to the risk of reactivation.
• If the interferon-gamma release assay shows a positive result at the Screening Visit the patient may only be included in the trial if the tuberculosis is latent and all of the following 3 conditions are true: (i) Chest X-ray does not show evidence suggestive of active tuberculosis. (ii) There are no clinical signs and symptoms of pulmonary and/or extra-pulmonary tuberculosis. (iii) Documented receipt of one of the following prophylactic treatment regimens: Oral daily isoniazid for 6 months or Oral daily rifampin for 4 months or Isoniazid and rifapentine weekly for 3 months. The IMP can only be administered to a participant with a positive test result in the interferon-gamma release assay (or an indeterminate result if only 1 test is done, or 2 indeterminate results if a second test is done after the first indeterminate test result) after the approval of a tuberculosis specialist.
• 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)

Sponsors & Collaborators

• medac GmbH: lead

Study Sites (30)

MU Dr. Petr Arenberger, DrSc. MBA

Prague, Praha 1, 11000, Czechia

RECRUITING

Synexus Czech s.r.o.

Prague, Praha 2, 12000, Czechia

TERMINATED

Praglandia s.r.o.

Prague, Praha 5, 15000, Czechia

RECRUITING

AGE Centrum s.r.o.

Olomouc, 77900, Czechia

WITHDRAWN

CCR Ostrava s.r.o,

Ostrava, 702 00, Czechia

RECRUITING

CCR Czech Pardubice a.s.

Pardubice, 53000, Czechia

RECRUITING

Clintrial s.r.o.

Prague, 10000, Czechia

RECRUITING

Dermatology clinic MUDr. Blanka Havlickova

Prague, 11000, Czechia

RECRUITING

Centre Hospitalier Universitaire de Bordeaux - Hopital Saint Andre

Bordeaux, 33075, France

WITHDRAWN

Centre Hospitalier universitaire (CHU) de Clermont Ferrand Hopital d'Estaing

Clermont-Ferrand, 63003, France

WITHDRAWN

Centre Hospitalier Universitaire De Nantes

Nantes, 44093, France

WITHDRAWN

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

RECRUITING

Ospedale San Donato di Arezzo

Arezzo, 52100, Italy

RECRUITING

Azienda Ospedaliera Universitaria di Ferrara Arcispedale Sant' Anna

Ferrara, 44124, Italy

WITHDRAWN

Ospedale Piero Palagi

Florence, 50125, Italy

WITHDRAWN

Universita degli Studi della Campania "Luigi Vanvitelli" - Azienda Ospedaliera Universitaria

Naples, 80138, Italy

WITHDRAWN

Azienda Ospedaliero-Universitaria di Parma

Parma, 43126, Italy

WITHDRAWN

Azienda Ospedaliero Universitaria Pisana (AOUP)

Pisa, 56126, Italy

RECRUITING

Synexus Polska Sp. z o.o. in Czestochowa

Częstochowa, 42-202, Poland

RECRUITING

Synexus Polska Sp. z o.o. Oddzial w Gdansku

Gdansk, 80-382, Poland

RECRUITING

Synexus Polska Sp. z o.o. Oddzial w Katowicach

Katowice, 40-040, Poland

RECRUITING

Angelius Badania Kliniczne

Katowice, 40-611, Poland

RECRUITING

Synexus Polska Sp. z. o.o. Oddzial W Lodzi

Lodz, 90-127, Poland

RECRUITING

LUXDERM Specjalistyczny Gabinet Dermatologiczny Prof. dr hab. n. med. Dorota Krasowska

Lublin, 20-573, Poland

RECRUITING

Klinika Zdybski

Lublin, 20-607, Poland

RECRUITING

Twoja Klinika

Mikołów, 43-190, Poland

RECRUITING

Synexus Polska Sp z o.o. Oddzial W Poznaniu

Poznan, 60-702, Poland

RECRUITING

Laser Clinic

Szczecin, 70-332, Poland

RECRUITING

Synexus Polska Sp. Z o.o. Odział w Warszawie

Warsaw, 02-672, Poland

RECRUITING

Klinika Ambroziak Dermatologia

Warsaw, 02-953, Poland

WITHDRAWN

MeSH Terms

Interventions

Methotrexate

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Audrey Nosbaum, MD PhD

  Université Lyon 1 / INSERM U1111 - CIRI / Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medac Clinical Trial Information

CONTACT

+49 (0)4103 8006; ClinicalTrialInformation@medac.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: February 2, 2024
• Study Start: February 27, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 27, 2025

Record last verified: 2025-08

Locations

CZ (8); IT (6); FR (4); PL (12)