Overview
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
Status:
Unknown status
Unknown status
Trial end date:
2020-10-01
2020-10-01
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 4Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Assistance Publique Hopitaux De MarseilleTreatments:
Methotrexate
Criteria
Inclusion Criteria:- Male or female patients aged 18 years or older
- Patients with moderate to severe chronic plaque psoriasis with or without psoriatic
arthritis AND who had started any first line of anti TNF alpha according to the
labeling of these drugs BEFORE the study (i. e. the study will be restricted to anti
TNF alpha naïve patients (first course). Patients who have been previously treated
with any other non anti TNFA alpha biopharmaceutical (ustekinumab or anti IL17-
secukinumab, ixekizumab, brodalumab) as a first line of biotherapy for psoriasis could
be enrolled) after a wash out period of at least 5 half life time of the drug i.e. 16
weeks before inclusion
- 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 with previous failure or intolerance but no absolute contraindication to
previous methotrexate medication for psoriasis can be enrolled, on the condition that
methotrexate (whatever the dose) has been stopped at least two months before the
inclusion.
- For patients who have never been previously treated with MTX, taking a test dose of
MTX (2.5 mg to 5 mg) with normality of the laboratory tests conducted one week to
remove a reaction idiosynchrasie before inclusion in the protocol
- Patients should be affiliated to the French Social Security system
- Patients who have given written consent for the study
Exclusion Criteria:
- 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)
- Hemoglobin <8.5g/dL (85.0 g/L)
- Creatinine clearance <40ml/min (Cockcroft formula)
- For women: pregnant or breast feeding
- Patients who have an active or serious infection or history of infections (bacterial,
viral, fungal or mycobacteria), requiring hospitalization or intra venous
anti-infectives infusion within 4 weeks prior to the baseline,
- Patients who have primary or secondary active immunodeficiency
- Patients who had live vaccine administration within 4 weeks prior to baseline
- Patients who have any current or active cancer (with the exception of patient with
successfully treated basal cell carcinoma or in situ cervix carcinoma)
- Patients who had history of malignancy within 5 years prior to the trial that could
contraindicate the use of an immunosuppressant
- Patients who will not be available for protocol which require study visits or
procedures
- Patients who is not affiliated to the French Social Security system
- Patients unable to give informed consent and/or comply with all required study
procedures