Clinical trial NCT06239311: Efficacy and Safety of Methotrexate Versus Placebo in Adults With Atopic Dermatitis.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Moderate to Severe Atopic Dermatitis
Lead sponsor: medac GmbH
Sponsor class: INDUSTRY
First posted: 2024-02-02
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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

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. If the positive interferon-gamma release assay shows a positive result at the Screening Visit the participant may only be included in the trial if the tuberculosis is latent and all of the following 3 conditions are true

  1. Chest X-ray does not show evidence suggestive of active tuberculosis.
  2. There are no clinical signs and symptoms of pulmonary and/or extra-pulmonary tuberculosis.
  3. Documented receipt of one of the following prophylactic treatment regimens: i. Oral daily isoniazid for 6 months or ii. Oral daily rifampin for 4 months or iii. Isoniazid and rifapentine weekly for 3 months
* 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
* 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 17. 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 janus kinase (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
* 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

Primary outcomes:
measure: Eczema Area and Severity Index (EASI) 75 response at Trial Week 16 Visit
timeFrame: Trial Week 16
Secondary outcomes:
measure: Improvement from baseline of at least 50% in the Eczema Area and Severity Index (EASI 50 response)
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Improvement from baseline of at least 75% in the Eczema Area and Severity Index (EASI 75 response)
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 24
measure: Improvement from baseline of at least 90% in the Eczema Area and Severity Index (EASI 90 response)
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Change from baseline in the Eczema Area and Severity Index (EASI) score.
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Scoring Atopic Dermatitis (SCORAD) 50 response
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Scoring Atopic Dermatitis (SCORAD) 75 response
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16,
measure: Change in Scoring Atopic Dermatitis (SCORAD) score from baseline
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Investigator Global Assessment (IGA) response
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16, Trial Week 24
measure: Pruritus Numerical Rating Scale (NRS) response
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16, Trial Week 24
measure: Change from baseline in Pruritus Numerical Rating Scale (NRS) score
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Patient-oriented Eczema Measure (POEM) response
timeFrame: Trial Week 8, Trial Week 16
measure: Change from baseline in POEM score
timeFrame: Trial Week 8, Trial Week 16
measure: Adverse events (AE), treatment-related AEs, serious adverse events (SAEs) and serious adverse reactions (SARs)
timeFrame: Trial Week 16, Trial Week 20, Trial Week 24, Trial Week 33
measure: Dermatology Life Quality Index (DLQI) response
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Change from baseline in Dermatology Life Quality Index (DLQI) score.
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Change from baseline in Scoring Atopic Dermatitis (SCORAD) sleep score
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Change from baseline in Work Productivity and Activity Impairment: General Health (WPAI:GH)
timeFrame: Trial Week 8, Trial Week 16
measure: Change from baseline in Hospital Anxiety and Depression (HADS) score and subscales
timeFrame: Trial Week 8, Trial Week 16
measure: Change from baseline in European Quality of Life (EuroQoL) Group 5 Dimension 5 Levels (EQ-5D-5L)
timeFrame: Trial Week 8, Trial Week 16
measure: Change from baseline in Atopic Dermatitis Control Tool (ADCT) score
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
measure: Eczema Area and Severity Index (EASI) 75 response at Trial Week 24 and the Follow-up Visit (Week 33)
timeFrame: Trial Week 24, Trial Week 33
measure: Scoring Atopic Dermatitis (SCORAD) 90 response
timeFrame: Trial Week 4, Trial Week 8, Trial Week 12, Trial Week 16
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: MU Dr. Petr Arenberger, DrSc. MBA
state: Praha 1
city: Prague
country: Czechia
facility: Synexus Czech s.r.o.
state: Praha 2
city: Prague
country: Czechia
facility: Praglandia s.r.o.
state: Praha 5
city: Olomouc
country: Czechia
facility: AGE Centrum s.r.o.
city: Ostrava
country: Czechia
facility: CCR Ostrava s.r.o,
city: Pardubice
country: Czechia
facility: CCR Czech Pardubice a.s.
city: Prague
country: Czechia
facility: Clintrial s.r.o.
city: Prague
country: Czechia
facility: Dermatology clinic MUDr. Blanka Havlickova
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Saint Andre
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier universitaire (CHU) de Clermont Ferrand Hopital d'Estaing
city: Nantes
country: France
facility: Centre Hospitalier Universitaire De Nantes
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Arezzo
country: Italy
facility: Ospedale San Donato di Arezzo
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria di Ferrara Arcispedale Sant' Anna
city: Firenze
country: Italy
facility: Ospedale Piero Palagi
city: Naples
country: Italy
facility: Universita degli Studi della Campania "Luigi Vanvitelli" - Azienda Ospedaliera Universitaria
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana (AOUP)
city: Czestochowa
country: Poland
facility: Synexus Polska Sp. z o.o. in Czestochowa
city: Gdańsk
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Gdansku
city: Katowice
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Katowicach
city: Katowice
country: Poland
facility: Angelius Badania Kliniczne
city: Lodz
country: Poland
facility: Synexus Polska Sp. z. o.o. Oddzial W Lodzi
city: Lublin
country: Poland
facility: LUXDERM Specjalistyczny Gabinet Dermatologiczny Prof. dr hab. n. med. Dorota Krasowska
city: Lublin
country: Poland
facility: Klinika Zdybski
city: Mikołów
country: Poland
facility: Twoja Klinika
city: Poznan
country: Poland
facility: Synexus Polska Sp z o.o. Oddzial W Poznaniu
city: Szczecin
country: Poland
facility: Laser Clinic
city: Warszawa
country: Poland
facility: Synexus Polska Sp. Z o.o. Odział w Warszawie
city: Warszawa
country: Poland
facility: Klinika Ambroziak Dermatologia
Study officials:
affiliation: Université Lyon 1 / INSERM U1111 - CIRI / Hospices Civils de Lyon
name: Audrey Nosbaum, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: