Intensive Treatment to Reach the Target With Golimumab in ulcErative coliTis - In-TARGET
Condition: ULCERATIVE COLITIS
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 4

Summary: 
      PHASE: IV

      TYPE OF STUDY: With direct benefit

      DESCRIPTIVE: multicenter, open-label, uncontrolled trial

      INCLUSION CRITERIA: Adults with moderate to severe ulcerative colitis who failed
      corticosteroids and immunosupressive therapy, or are intolerant to immunosuppressors. All
      included patients will be naïve to anti-TNF therapy. Active disease at golimumab treatment
      initiation defined as a MAYO score ≥6 and with an endoscopic sub score ≥2.

      OBJECTIVE: To determine the proportion of patients with Continuous Clinical Response (CCR)
      and endoscopic remission after one year of golumimab at week 54.

      STUDY DESIGN:

      Induction Phase :

      Week 0: golimumab 200mg- Week 2: golimumab 100 mg- Week 6: golimumab 50 mg

      Maintenance Phase I : Week 10-Week 54 Week 10-Week 54 • Patients with primary clinical
      response*: Standard regimen with golimumab 50 mg Q4W (or 100 mg Q4W if > 80 kg)

        -  Patients without primary clinical response at week 10 or with flare between week 10-week
           54*: Optimization to 100 mg Q4W (or combination therapy with azathioprine if > 80 kg or
           switch from azathioprine to methotrexate if already on azathioprine at golimumab
           initiation or patient with known intolerance to thiopurines)

        -  Early escape at Week 18: Primary non-responders who are still not responding at week 18
           to dose optimization at Weeks 10 and 14 will be considered treatment failures and will
           be followed up (call or visit) at week 54 for safety.

             -  Clinical response is defined as a decrease from baseline in the Mayo score ≥30% and
                ≥3 points, accompanied by either a rectal bleeding sub score of 0 or 1 or a
                decrease from baseline in the rectal bleeding sub score ≥1

      Intermittent Phase II : Week 54-Week 108

      • Patients with CCR and MH at week 54 and on golimumab 50 mg every 4 weeks: Stop golimumab
      and continuation of thiopurines or methotrexate if on combination therapy

      • Patients with CCR and MH at week 54 and on golimumab 100 mg every 4 weeks: De-escalation to
      50 mg every 4 weeks and continuation of thiopurines or methotrexate if on combination therapy

      • Restart/Escalate golimumab on flare (defined in section 4 of the protocol) to the phase I
      dose; 50 mg q4wk or 100mg q4wk (similar to the phase I regimen)
    

Detailed description: 
      NUMBER OF PATIENTS: 200 patients

      INCLUSION PERIOD: 33 months

      STUDY DURATION: 57 months

      MAIN EVALUATION Primary endpoints

      • Week 10-54: proportion of patients in CCR and with MH (endoscopic Mayo score of 0 or 1) at
      week 54

      Data base lock, data analysis and display (publication) will happen when all included
      subjects have completed the 108-week visit.

      SECONDARY EVALUATION

      For all included patients:

        -  Phase II (week 54-108): proportion of patients in CCR with MH (endoscopic Mayo score of
           0 or 1) at week 108, after discontinuation or dose de-escalation (from 100 to 50 mg) of
           golimumab treatment at year 1 in the subgroup of patients in CCR and with MH (endoscopic
           Mayo score of 0 or 1) at week 54

        -  Factors associated with treatment success (see primary endpoint)

        -  Efficacy of dose optimization in patients who loose response between week 10 and 54

        -  Clinical remission at week 54 • Clinical remission at week 108 • Partial MAYO score at
           week 54 and 108 • PRO2 (Partial Mayo minus PGA) at week 54 and 108 • CCR between study
           inclusion and week 54 and 108 • Steroid-free clinical remission at week 54 and 108 • MH
           (endoscopic score MAYO 0-1) at week 54 and 108 • Changes in faecal calprotectin levels
           from baseline to week 54 and 108 • Colectomy between W0 and W54 and 108

        -  UC-related hospitalizations throughout the trial • Histological remission9 at W54 and
           108

        -  PRO: Fatigue (FACIT), disability (IBD Disability index), QoL (SHS-IBD VAS)

        -  PK data (golimumab trough levels and antibodies against golimumab)

        -  Proportion of late responders being in Clinical Response from week 18 to week 54 and
           with MH at week 54 following treatment intensification in Maintenance Phase

      For the subgroup of patients who are primary non-responders to golimumab at week 10, we will
      assess the efficacy of treatment optimization, including the percentage of patients achieving
      continuous clinical response and endoscopic remission at one year.
    

Intervention name(s): GOLIMUMAB
Intervention type(s): Drug
Intervention description(s): Increase/ or Decrease/ Interruption Dose of Golimumab depending on Continuous Clinical Response or Relapse
Intervention MeSH terms: Golimumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: UC, IBD