Methotrexate in Induction and Maintenance of Steroid Free Remission in Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 2

Summary: 
      There are fewer therapeutic options for patients with active ulcerative colitis (UC) compared
      to patients with active Crohn's disease (CD) and the investigators are facing a persistent
      unmet need for additional effective and affordable therapies for patients with UC.
      Methotrexate (MTX) 25 mg once weekly administered subcutaneously (sq) or intramuscularly (im)
      is an efficient therapy to induce and maintain steroid free remission in patients with CD. To
      evaluate the efficacy of a similar approach in patients with active ulcerative colitis the
      investigators conduct a double-blind, placebo controlled, randomized, multicenter, parallel
      group trial to investigate the safety and efficacy of 25 mg MTX applied subcutaneously once
      weekly in patients with active UC, who either failed 5-ASA therapy, or are steroid dependent
      or are intolerant or not responding to azathioprine/6-mercaptopurine therapy or have no
      response/ lost response to infliximab prior to the study inclusion. The study is designed as
      a drug withdrawal trial and includes two periods, the Induction Period (week 0-16) and the
      Maintenance Period (week 17-48). In the open label Induction Period every patient will
      receive a steroid taper, MTX 25 mg sq once weekly + daily folic acid 1 mg tablets for the
      induction of clinical response or remission. Patients responding to the open label MTX
      therapy and being off steroids between week 12-16 will be randomized at week 16 1:1 to
      Placebo sq once weekly + daily folic acid 1 mg tablets + 2.4 g mesalamine or to MTX 25 mg sq
      once weekly + daily folic acid 1 mg tablets+ 2.4 g mesalamine. The Specific Aims of the trial
      are: i) To evaluate the safety and tolerability of 25 mg MTX applied sq once weekly over a
      time period of 48 weeks; ii) To evaluate the relapse-free survival of MTX maintenance therapy
      compared to placebo over a time period of 32 weeks; iii) To evaluate the efficacy of MTX over
      a time period of 16 weeks to induce steroid free remission; iiii) To establish a DNA, plasma
      and serum library to enable the evaluation of clinical and pharmacogenomic models to predict
      the response to MTX therapy in patients with UC. With 25-30 participating centers actively
      enrolling, the investigators anticipate to complete enrollment for this study in a time
      period of 3 years. Completion of this trial will define the therapeutic value of MTX in UC,
      potentially changing the current therapeutic strategy in UC.
    


Intervention name(s): Methotrexate
Intervention type(s): Drug
Intervention description(s): Induction period (week 1-16) (Open label):
25 mg MTX sq once weekly + Steroid taper + 1 mg folic acid daily
Maintenance period (week 17-48) (Randomization):
25 mg MTX sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine or Placebo sq once weekly + 1 mg folic acid daily + 2.4 g mesalamine
Other intervention name(s): Placebo
Intervention MeSH terms: Methotrexate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment