Intensive Treatment to Reach the Target With Golimumab in ulcErative coliTis - In-TARGET
- Registration Number
- NCT02425865
- Lead Sponsor
- Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 202
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description open-label, uncontrolled trial GOLIMUMAB All patients will receive Standard regimen with golimumab 50 mg Q4W, or 100 mg Q4W if \> 80 kg
- Primary Outcome Measures
Name Time Method Continuous Clinical Response and Endoscopic Remission Week 54 proportion of patients in CCR and with MH (endoscopic Mayo score of 0 or 1) at week 54
- Secondary Outcome Measures
Name Time Method Continuous Clinical Response and Endoscopic Remission after discontinuation or de- escalation of golimumab Week 108 proportion of patients maintaining continuous clinical response and endoscopic remission at week 108, after discontinuation or de-escalation of golimumab treatment at year 1 in the subgroup of patients in continuous clinical response (CCR) and with mucosal healing (endoscopic Mayo score of 0 or 1) at week 54
Clinical remission at week 54 week 54 proportion of patient with clinical remission (partial Mayo score) at week 54
Changes in faecal calprotectin levels from baseline at week 54 and 108 week 108 Evolution of faecal calprotectin levels from baseline at week 54 and 108 according the clinical and endoscopic remission
Colectomy between W0 and W54 and 108 week 108 Proportion of patient with colectomy between W0 and W54 and W108
Histological remission at W54 and 108 week 108 Proportion of patient with histological remission at W54 and W108
MH (endoscopic score MAYO 0-1) at week 54 and 108 week 108 proportion of patient with MH (endoscopic score MAYO 0-1) at week 54 and 108
Efficacy of dose optimization in patients who loose response between week 10 and 54 Week 54 proportion of patients maintaining continuous clinical response after dose optimization in patients who loose response between week 10 and 54
PRO2 (Partial Mayo minus PGA) at week 54 and 108 week 108 Evolution of PRO2 (Partial Mayo minus PGA) at week 54 and 108 according the clinical and endoscopic remission
CCR between study inclusion and week 54 and 108 week 108 proportion of patient with CCR at week 54 and 108
Clinical remission at week 108 week 108 proportion of patient with clinical remission (partial mayo score) at week 108
Steroid-free clinical remission at week 54 and 108 week 108 proportion of patient with steroid-free clinical remission at week 54 and 108
UC-related hospitalizations throughout the trial week 108 Proportion of patient with UC-related hospitalizations throughout the trial
Late responders being in Clinical Response from week 18 to week 54 and with MH at week 54 following treatment intensification in Maintenance Phase week 108 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
PRO: Fatigue (FACIT), disability (IBD Disability index), QoL (SHS-IBD VAS) week 108 Evolution of PRO: Fatigue (FACIT), disability (IBD Disability index), QoL (SHS-IBD VAS) according the clinical and endoscopic remission
PK data (golimumab trough levels and antibodies against golimumab) week 108 Evolution of PK (golimumab trough levels and antibodies against golimumab) according the clinical and endoscopic remission
Trial Locations
- Locations (23)
CHU Dinant Godinne UCL Namur
🇧🇪NAmur, Belgium
CHU de Saint Etienne- Hopital Nord
🇫🇷Saint-Priest-en-Jarez, France
Chu Strasbourg
🇫🇷Strasbourg, France
Chu Besancon
🇫🇷Besançon, France
CHU de Colmar- Hopital Trousseau Medecine A
🇫🇷Colmar, France
CHU de NICE- Hopital Archet 2
🇫🇷Nice, France
Chu Reims
🇫🇷Reims, France
CHU RENNES - Hopital Pontchaillou
🇫🇷Rennes, France
CHU de TOULOUSE
🇫🇷Toulouse, France
CHU LIEGE - Sart Tilman
🇧🇪Liege, Belgium
Caen Unversity Hospital
🇫🇷Caen, France
APHP- Hopital BEAUJON
🇫🇷Clichy, France
CHRU Lille
🇫🇷Lille, France
CHU Amiens
🇫🇷Amiens, France
CHU Clermont Ferrand
🇫🇷Clermont-Ferrand, France
CHU de Tours - Hopital Trousseau
🇫🇷Tours, France
CHU de Montpellier- Hopital saint Eloi
🇫🇷Montpellier, France
CHU de Nimes- Hopital Carémeau
🇫🇷Nîmes, France
CHU NANTES - Hôpital Hôtel Dieu
🇫🇷Nantes, France
APHP- Hopital BICHAT
🇫🇷Paris, France
CHU Bordeaux- Hopital Haut Levèque
🇫🇷Pessac, France
CHU LYON- Hopital Lyon Sud
🇫🇷Pierre-Bénite, France
CHU NANCY - Hopital Brabois
🇫🇷Vandoeuvre Les Nancy, France