Trial in Patients With Psoriasis Treated With Methotrexate Using an Optimized Treatment Schedule (METOP)

NCT02902861 | Completed Phase 3

• 2 other identifiers: 165-0012012-002716-10
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, multinational (12 centers planned, in Germany 9 centers and in France, the Netherlands and the United Kingdom (UK) 1 center in each country respectively), randomized, double-blinded, placebo-controlled study. The primary objective is to evaluate the efficacy of methotrexate (MTX) in patients with moderate to severe Psoriasis compared to Placebo as assessed by the primary endpoint "75% reduction of Psoriasis Area Severity Index" (PASI 75 ) during a 16 week treatment phase. As secondary objectives the safety and efficacy of the optimized treatment schedule will be assessed using multiple methods (e.g. (Serious) Adverse Events ((S)AE) occurrence and questionnaires)

Conditions

Psoriasis Vulgaris

Outcome Measures

Primary Outcomes (1)

• Difference in 75% reduction of Psoriasis Area Severity Index (PASI75) responder rate between treatment arms

  week 16

Secondary Outcomes (19)

• Difference in PASI75 responder rate between treatment arms

  weeks 52

• Difference in 50% reduction of Psoriasis Area Severity Index (PASI50)

  weeks 15 and 52

• Difference in 90% reduction of Psoriasis Area Severity Index (PASI90)

  weeks 15 and 52

• PASI75 in placebo arm (cross-over)

  weeks 32

• Difference in Nail Psoriasis Severity Index (NAPSI)

  weeks 16 and 52

Study Arms (2)

methotrexate

ACTIVE COMPARATOR

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.

Drug: Methotrexate

Placebo (NaCl-Solution)

PLACEBO COMPARATOR

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.

Drug: Placebo ( for Methotrexate)

Interventions

Methotrexate DRUG

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

Also known as: MTX

methotrexate

Placebo ( for Methotrexate) DRUG

NaCl-Solution manufactured to mimic Methotrexate

Placebo (NaCl-Solution)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prof. Kristian Reich: lead

Study Sites (1)

Psoriasis-Zentrum, Universitäts-Hautklinik Kiel

Kiel, Schleswig-Holstein, 24105, Germany

Location

MeSH Terms

Interventions

Methotrexate

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ulrich Mrowietz, Professor

  Psoriasis-Zentrum, Universitäts-Hautklinik Kiel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: September 16, 2016
• Study Start: February 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: May 1, 2015
• Last Updated: September 16, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)