A Phase 3, Randomised, 2-arm, Parallel-group, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Subcutaneous Methotrexate Versus Placebo in Moderate to Severe Atopic Dermatitis.

medac GmbH30 sites in 4 countries277 target enrollmentFebruary 27, 2024

ConditionsModerate to Severe Atopic Dermatitis

InterventionsMethotrexate Placebo

Overview

Phase: Phase 3
Intervention: Methotrexate
Conditions: Moderate to Severe Atopic Dermatitis
Sponsor: medac GmbH
Enrollment: 277
Locations: 30
Primary Endpoint: Eczema Area and Severity Index (EASI) 75 response at Trial Week 16 Visit
Status: Recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 27, 2024

End Date

April 1, 2027

Last Updated

8 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

medac GmbH

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•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

Exclusion Criteria

•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.

Arms & Interventions

Methotrexate

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.

Intervention: Methotrexate

Placebo

Participants will receive 16 to 24 weekly subcutaneous injections

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: Trial Week 16

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).

Secondary Outcomes

Change from baseline in the Eczema Area and Severity Index (EASI) score.(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
Change from baseline in Pruritus Numerical Rating Scale (NRS) score(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
Dermatology Life Quality Index (DLQI) response(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
Change from baseline in Dermatology Life Quality Index (DLQI) score.(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
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)
Scoring Atopic Dermatitis (SCORAD) 75 response(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16,)
Change in Scoring Atopic Dermatitis (SCORAD) score from baseline(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
Change from baseline in POEM score(Trial Week 8, Trial Week 16)
Change from baseline in Scoring Atopic Dermatitis (SCORAD) sleep score(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
Scoring Atopic Dermatitis (SCORAD) 90 response(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
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)
Pruritus Numerical Rating Scale (NRS) response(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16, Trial Week 24)
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)
Scoring Atopic Dermatitis (SCORAD) 50 response(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
Investigator Global Assessment (IGA) response(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16, Trial Week 24)
Adverse events (AE), treatment-related AEs, serious adverse events (SAEs) and serious adverse reactions (SARs)(Trial Week 16, Trial Week 20, Trial Week 24, Trial Week 33)
Patient-oriented Eczema Measure (POEM) response(Trial Week 8, Trial Week 16)
Change from baseline in Hospital Anxiety and Depression (HADS) score and subscales(Trial Week 8, Trial Week 16)
Change from baseline in Atopic Dermatitis Control Tool (ADCT) score(Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16)
Eczema Area and Severity Index (EASI) 75 response at Trial Week 24 and the Follow-up Visit (Week 33)(Trial Week 24, Trial Week 33)
Change from baseline in Work Productivity and Activity Impairment: General Health (WPAI:GH)(Trial Week 8, Trial Week 16)
Change from baseline in European Quality of Life (EuroQoL) Group 5 Dimension 5 Levels (EQ-5D-5L)(Trial Week 8, Trial Week 16)