Multicenter Randomized Double Blind Controlled-study to Assess the Potential of Methotrexate Versus Placebo to Improve and Maintain Response to Anti TNF- Alpha Agents in Adult Patients With Moderate to Severe Psoriasis

NCT02829424 | Terminated Phase 4

• 2 other identifiers: 2014-502015-003891-54
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The overall purpose of this trial is to assess efficacy and safety of the combination of low doses of Methotrexate (MTX) with anti Tumor Necrosis Factor (TNF) alpha to improve initial efficacy and maintenance rate of anti-TNF alpha treatment in patients with psoriasis.

Conditions

Psoriasis

Outcome Measures

Primary Outcomes (1)

• Loss of response from the index anti TNF alpha

  The primary endpoint is the loss of response from the index anti TNF alpha is defined as the time (or time interval) between baseline and the loss of PASI 75 response (loss of the improvement of at least 75% of the initial disease severity (loss of PASI 75).The respective loss of response between MTX and placebo in combination with the anti TNF alpha will be assessed for both groups during month (M) 24. The survival curves will be compared between the groups (MTX and placebo) using the log rank test.

  24 months

Secondary Outcomes (5)

• Initial response to the index anti TNF alpha

  4 months

• The maintenance of response rates proportion of patients who are still treated with the index anti TNF alpha agent without any drug adjustment

  24 months

• Assessment of patient's quality of life using the Dermatology Quality of Life (DLQI)

  24 months

• Assessment of the study drugs 'safety: number of Adverse Events (AE) and serious adverse events (SAE), as well as the proportion of discontinuation due to AEs and/or SAEs

  24 months

• Assessment of the sutdy drugs' (MTX and MTX placebo) tolerability by measuring the possible changes in vital signs and occurence of AE such as asthenia, digestive tolerance, headache.

  24 months

Study Arms (2)

Experimental group

ACTIVE COMPARATOR

Use of low dose methotrexate (MTX) in psoriasis patients receiving an anti TNF alpha agent according to the approved indication: etanercept- Enbrel®, adalimumab- Humira ®, infliximab -Remicade ®, infliximab's biosimilar- Inflectra®, Remsima®, or any other biosimilar or branded biological agent All anti TNF alpha agents will have to be prescribed in the same administration modality and dosing regimen than in the control group and according to the Summary of Product Characteritics (SmPC) MTX: 15 mg a week orally: on a fixed day of the week defined for each patient In patients receiving an anti TNF alpha according to the SmPC, MTX will be initiated within 7 days after the start of the anti TNF alpha agent

Drug: Methotrexate

Control group

PLACEBO COMPARATOR

Use of placebo- MTX in psoriasis patients receiving anti TNF alpha agent according to the approved indication: etanercept- Enbrel®, adalimumab- Humira ®, infliximab -Remicade ®, infliximab's biosimilar- Inflectra®, Remsima®, or any other biosimilar or branded biological agent All anti TNF alpha agents will have to be prescribed in the same administration modality and dosing regimen than in the experimental group and according to the SmPC Placebo-MTX orally: on a fixed day of the week defined for each patient In patients receiving an anti TNF alpha according to the SmPC, MTX-placebo will be initiated within 7 days after the start of the anti TNF alpha agent

Drug: Methotrexate Placebo

Interventions

Methotrexate DRUG

Use of low dose methotrexate (MTX) in psoriasis patients receiving an anti TNF alpha agent

Experimental group

Methotrexate Placebo DRUG

Use of placebo- MTX in psoriasis patients receiving anti TNF alpha agent according to the approved indication

Control group

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged 18 years or older
• No significant anomalies from a blood sampling performed within 15 days before patient selection that could lead to MTX contraindication
• Patients with an EARLY start of anti TNF alpha, i. e. within the 7 days preceding the first study drug (methotrexate or placebo) administration
• Male or female patients agreeing to use a reliable method of birth control during the study
• Male patients agreeing to use a reliable method of birth control during the study i. e. preservative and for at least 6 months following the last dose of investigational product, the patient's partner treated by methotrexate must be notified of the teratogenic risk of methotrexate and should be under effective contraception throughout the study
• Female patients:
• Are women of childbearing potential who are negatively tested for pregnancy and agree to use a reliable method of birth control (every month) or remain abstinent during the study and for at least 6 months following the last dose of investigational product, whichever is longer. Methods of contraception considered acceptable include oral contraceptives, contraceptive patch, intrauterine device, vaginal ring.
• And Negative serum b-Human Chorionic Gonadotrophin (B-HCG) test at screening Or
• Women of non-childbearing potential, defined as:
• Women who have had a surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation) Or Women \> = 60 years of age Or Women \>=40 and \< 60 years who have had a cessation of menses for \>=12 months and a follicule stimulating hormone (FSH) test confirming non - childbearing potential
• Patients should be affiliated to the French Social Security system
• Patients who have given written consent for the study

You may not qualify if:

• Patients with isolated pustular, erythrodermic and or guttate forms of psoriasis
• Patients with prior use of any anti TNF alpha
• Patients who have known active liver disease (with the exception of a simple liver steatosis, transaminases and/or alkaline phosphatases \> 2 ULM ) or history of liver disease in the past 2 years, whatever the related diagnosis but which could interfere with MTX safety and according to the summary of the SmPC
• Intake of restricted medications (cf section VIII.5.) or other drugs considered likely to interfere with the safe conduct of the study, as assessed by the investigator and according to the Summary of the Product Characteristics (SmPC), including any drug intakes that could interfere with methotrexate metabolism or that could enhance liver and /or hematologic toxicity and according to the SmPC
• Patient with evidence or positive test for HIV, Hepatitis C virus, Hepatitis B virus (patients who are negative for hepatitis B surface antigen but positive for anti-hepatitis B anti body (HBsAb+ and HBcAb+) and negative for serum HBV DNA may participate in the study
• High alcohol intake defined as more than 60 g of daily intake (approx daily intake of 0.5 l of wine or equivalent),
• Patients who have a known allergy or hypersensitivity to MTX
• Patients who have a known serious adverse event to MTX prior to the trial leading to MTX discontinuation in the past
• Presence of significant hematologic or renal disorder or abnormal laboratory values at screening that, in the opinion of the investigator is associated with an unacceptable risk to the patient to participate in the study
• Clinical laboratory test results at screening that are outside a normal reference rating for the population and are considered clinically significant, or/and have any of the following specific abnormalities:
• Total white blood cell count \<3G/L
• Neutrophil count \< 1.5 G/l
• Lymphocytes count \< 0.5G/l
• Platelet count \< 100 G/l
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\>3 times the upper limit of normal (ULM)

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13385, France

Location

MeSH Terms

Conditions

Psoriasis

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Catherine GEINDRE

  Assistance Publique Hôpitaux de Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2016
• First Posted: July 12, 2016
• Study Start: January 23, 2017
• Primary Completion: January 10, 2023
• Study Completion: February 10, 2024
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

FR (1)