- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02902861
Trial in Patients With Psoriasis Treated With Methotrexate Using an Optimized Treatment Schedule (METOP) (METOP)
An International Prospective, Double-blind, Placebo-controlled Phase III Randomised Controlled Trial (RCT) in Patients With Moderate to Severe Psoriasis Are Treated With Subcutaneous (s.c.) Methotrexate Using an Optimized Treatment Schedule.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Schleswig-Holstein
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Kiel, Schleswig-Holstein, Germany, 24105
- Psoriasis-Zentrum, Universitäts-Hautklinik Kiel
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Are 18 years of age or older at time of informed consent; may be men or women.
- Are MTX naïve
- Moderate to severe plaques psoriasis (according rule of ten (PASI ≥10 or BSA ≥ 10 or DLQI ≥ 10) for at least 6 months with or without psoriatic arthritis (however, highly active psoriatic arthritis is excluded, defined by. > 5 swollen tender joints or soles and C-Reactive Protein (CRP) >2 x UNL) .
- Women of childbearing potential and all men must be using a highly effective method of contraception (pearl index < 1%) as defined blow and must agree to continue to use such measures and not become pregnant or plan a pregnancy until 6 months after receiving the last injection of Investigational Medicinal Product (IMP).Highly effective method is defined as: Use of oral, injected or implanted hormonal methods, intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Able to adhere to the study visit schedule and other protocol requirements.
- Capable of giving informed consent. The informed consent must be obtained prior to any study related procedures.
- Must avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during study.
- Must agree not to receive a live virus or live bacterial vaccination 4 weeks prior to the first IMP s.c. administration, during the trial and up to 3 months after the last injection.
- Chest X-ray investigation within the last 6 months prior to first s.c. administration of IMP and show no clinically relevant abnormalities
Exclusion Criteria:
- Currently have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular).
- Have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, (hydroxy-) chloroquine, or lithium).
- Are pregnant, nursing, or planning pregnancy (both men and women) while enrolled in the study.
Have screening laboratory test results for the following parameters outside the stated ranges (please refer also to :
- Hemoglobin < 10 g/dL
- White blood cells < 3.0 x 109/L
- Neutrophils < 1.5 x 109/L
- Platelets < 100 x 109/L
- Creatinine clearance (calculated according to Cockcroft-Gault) < 50 mL/min)
- Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Gamma Glutamyltransferase (γ-GT) levels must be > 2 times the upper limit of normal range
- Bilirubin > 5mg/dl (85,5 μmol/l)
- Hypalbuminemia <3,5 g/dl
- Have used any other IMP within the previous 4 weeks or 5 times the half-life of an investigational agent prior to the first s.c. administration of the IMP of this study, whichever is longer.
Not able or willing to wash out any prohibited medications as listed below.
- Any biologics; washout 5 times of half-life
- Phototherapy or any systemic medications that could affect the psoriasis (including but not limited to oral or injectable corticosteroids, retinoids, 1,25 dihydroxy vitamin D3 and analogues, sulfasalazine, hydroxyurea, or fumaric acid derivates), within 4 weeks
- Any topical medications that could affect the psoriasis (e.g. corticosteroids, anthralin, calcipotriene, topical vitamin D derivates, retinoids, tazarotene), within 2 weeks
- Any systemic immunosuppressants (e.g. azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, and tacrolimus) ,within 4 weeks
- lithium, antimalarial agents To be stopped directly prior to first s.c. administration of IMP
- Intramuscular gold ,Within 4 weeks Patients who take prohibited medications that cannot be washed out within 4 weeks or at least 5 times of the half-life of the investigational agent prior to first s.c.
administration of IMP should not be asked to participate in the trial.
- Have a history of chronic or recurrent infectious disease or had a serious infection or have been hospitalized or received i.v. antibiotics for the treatment of an infection within 2 months prior to screening.
- History of radiotherapy or planed concomitant radiotherapy
- Ulcers of the oral cavity (e.g. ulcerative stomatitis) and/or known gastrointestinal ulcer disease
- A known B12/cobalamin deficiency
- Known diagnosed ascites or pleural effusions
- Have a history of latent or active Tuberculosis (TB) (prior to screening).
- Have current signs or symptoms of severe, progressive, or uncontrolled renal (specifically with calculated creatinine clearance < 20), hepatic (especially with bilirubin > 5mg/dl (85,5 mol/l), hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
- Have any known malignancy or have a history of malignancy (with the exception of basal cell carcinoma, squamous cell carcinoma in situ of the skin, or cervical carcinoma in situ that has been treated with no evidence of recurrence, or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years prior to the first administration of study agent).
- Have shown a previous immediate hypersensitivity response, including anaphylaxis, to the folic acid
- Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins.
- Are known to have had a substance abuse (drug or alcohol) problem within the previous 12 months.
- Staff or relatives/partner of any clinical research site
Study Plan
How is the study designed?
Design Details
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: methotrexate
Once weekly (every 7 days) s.c.
administration of 17.5 mg MTX.
If PASI50 is not reached after 8 weeks (week 8) or PASI75 is not reached after 24 weeks, the dosing will be increased to 22.5 mg MTX/week.
If patients were already dosed with 22.5 mg MTX/week in week 24 and PASI50 is not reached, patients will be excluded from treatment.
Primary endpoint after 16 weeks.
|
methotrexate 50 mg/ml in syringes for sub-cutaneous injection; Once weekly (every 7 days) s.c.
administration of 17.5 mg MTX; If PASI50 is not reached after 8 weeks, the dosing will be increased to 22.5 mg
Other Names:
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PLACEBO_COMPARATOR: Placebo (NaCl-Solution)
Once weekly (every 7 days) s.c.
administration of 0.35 mL placebo If PASI50 is not reached after 8 weeks (week 8), the dosing will be increased to 0.45 mL placebo/week.
Primary endpoint after 16 weeks.
After 16 weeks patients will receive 17.5 mg MTX / week.
If PASI50 is not reached after 8 weeks of MTX treatment (week 24), uptitration to 22.5 mg MTX/ 0.45 mL Plac / week will be done.
Patients, who will reach PASI75 under placebo treatment after 16 weeks, will be dosed neither with placebo nor with MTX until relapse.
After relapse the patients will be dosed with a starting dose of 17.5 mg MTX / week.
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NaCl-Solution manufactured to mimic Methotrexate
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Difference in 75% reduction of Psoriasis Area Severity Index (PASI75) responder rate between treatment arms
Time Frame: week 16
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week 16
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in PASI75 responder rate between treatment arms
Time Frame: weeks 52
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weeks 52
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Difference in 50% reduction of Psoriasis Area Severity Index (PASI50)
Time Frame: weeks 15 and 52
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weeks 15 and 52
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Difference in 90% reduction of Psoriasis Area Severity Index (PASI90)
Time Frame: weeks 15 and 52
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weeks 15 and 52
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PASI75 in placebo arm (cross-over)
Time Frame: weeks 32
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weeks 32
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Difference in Nail Psoriasis Severity Index (NAPSI)
Time Frame: weeks 16 and 52
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weeks 16 and 52
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Difference in Body Surface Area Index (BSA)
Time Frame: weeks 16 and 52
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weeks 16 and 52
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Difference in Physician's Global Assessment (PGA)
Time Frame: weeks 16 and 52
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weeks 16 and 52
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Difference in Psoriatic Arthritis Index (PsA)
Time Frame: weeks 16 and 52
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weeks 16 and 52
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Difference in Patient's satisfaction with metex® pre-filled syringe (PSAT metex®)
Time Frame: weeks 16 and 52
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weeks 16 and 52
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Difference in Dermatology Life Quality Index (DLQI)
Time Frame: weeks 16 and 52
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weeks 16 and 52
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Difference in European Qualification-5D-Questionnaire (EQ-5D)
Time Frame: weeks 16 and 52
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weeks 16 and 52
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Safety and tolerability assessed by Adverse Events (AE)/ Serious Adverse Events (SAE) tolerability at the site of administration
Time Frame: week 0 - week 51
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week 0 - week 51
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Safety and tolerability assessed by laboratory values
Time Frame: week 0 - week 51
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week 0 - week 51
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local tolerability at the site of administration assessed by Erythema
Time Frame: week 0 - week 51
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Erythema (redness): diameter (mm) and severity from none to severe (0 = none, 1= mild, 2 = moderate 3 = severe) |
week 0 - week 51
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local tolerability at the site of administration assessed by Swelling
Time Frame: week 0 - week 51
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Swelling/Induration: diameter (mm) and severity from none to severe (0 = none, 1= mild, 2 = moderate 3 = severe) |
week 0 - week 51
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local tolerability at the site of administration assessed by Hematoma
Time Frame: week 0 - week 51
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Hematoma: yes/ no and if present diameter (mm)
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week 0 - week 51
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local tolerability at the site of administration assessed by Local Pain
Time Frame: week 0 - week 51
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Local pain - assessed by the study subject on a visual analogue scale (1-10)
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week 0 - week 51
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local tolerability at the site of administration assessed by Pruritus
Time Frame: week 0 - week 51
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Pruritus - assessed by the study subject on a visual analogue scale (1-10)
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week 0 - week 51
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Changes of levels of molecular biologic analysis
Time Frame: at baseline and 16 weeks
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at baseline and 16 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ulrich Mrowietz, Professor, Psoriasis-Zentrum, Universitäts-Hautklinik Kiel
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Skin Diseases, Papulosquamous
- Psoriasis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
Other Study ID Numbers
- 165-001
- 2012-002716-10 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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