A Trial COmparing staNdard of Care Versus Treat to Target With telemonitoRing and Patient Education in Patients With Ulcerative cOlitis Initiating Adalimumab

Study Overview
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Brief Summary
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PHASE: IV DESCRIPTIVE: Randomized, interventional, open label multicenter trial POPULATION: Moderate to severe ulcerative colitis STUDY TREATMENTS: Patients will all receive Adalimumab 160/80/40mg EOW until V1 (W14) followed by 40mg EOW until V2 (W26) and could be optimized up to 80mg EOW (or 40 EW according to patient and/or investigator preference) for two months and then could be optimized up to 80mg EOW (or 40 EW according to patient and/or investigator preference) and azathioprine (2.0/2.5 mg/kg/ day) or methotrexate (25 mg EW) until V3 (W 38). OBJECTIVES: To assess the impact of a treat to target treatment follow up by e-Monitoring and fecal calprotectin dosing at home associated to an appropriate patient education versus standard treatment follow up at W48 in patients requiring a treatment with adalimumab (Humira®).

Detailed Description
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NUMBER OF PATIENTS : 238 patients in 20 sites in France RECRUITMENT PERIOD : The trial duration for each patient will be 144 weeks MAIN ENDPOINT : At week 48 success defined by: Endoscopic remission defined by an endoscopic Mayo score 0 SECONDARY ENDPOINTS: At W48 Clinical remission (Clinical remission is defined as a total Mayo score ≤2 points, with no individual sub score >1, and a Mayo endoscopy sub score of 0 or 1) Remission without steroids Endoscopic healing rate with Mayo score 0 or 1 UCEIS score Histological healing (Nancy score) Remission rate and remission rate without steroids at study visits and W48 Quality of life evolution (evaluate visit W0 vs W14, W26, W38 and W48) Patients satisfaction Continuous response Safety and tolerability Anti-TNF pharmacokinetics Number of visits in trial Number of UC related hospitalizations Number of colectomies Treatment compliance (questionnaire) Patient adhesion (questionnaire) Medico-economic analysis

Official Title
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An Open-label Randomized Trial COmparing staNdard of Care Versus Treat to Target With telemonitoRing and Patient Education in Patients With Ulcerative cOlitis Initiating adaLimumab: The CONTROL Trial

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Adalimumab
* Diagnostic Test: Calprotectin
* Other: e-Monitoring
* Other: Therapy Education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with moderately-to-severely active Ulcerative Colitis (UC) who had an inadequate response to or failed to tolerate steroids and thiopurines (azathioprine or 6-mercaptopurine), methotrexate or vedolizumab or adults with moderately-to-severely active UC who had no response to an adequate steroid course Age ≥ 18 years and < 75 years Patients scheduled to start a treatment with adalimumab Naïve to anti-TNF therapy and other biologics known to be effective for UC (approved or investigational) except for vedolizumab Naïve to JAK inhibitors (approved or investigational) Moderately-to-severely active UC for at least 3 months with a Mayo score of 6-12 points (endoscopy subscore of at least 2) Established diagnosis of UC for at least 3 months (pancolitis, left-sided colitis, proctosigmoiditis and proctitis are allowed). Patient has to be treated with oral 5-ASA at time of inclusion regardless of the dose if no contra-indication. Azathioprine, 6-mercaptopurine or methotrexate will be stopped two weeks before inclusion. A contraceptive method during the whole trial for childbearing potential female Patient familiar with Smartphone and internet use Exclusion Criteria: Patients unable to give their consent (because of their physical or mental state). Absence of written consent. Pregnancy or breastfeeding. Patients with severe acute colitis or patients at imminent risk for colectomy. History of colectomy. History of colonic mucosal dysplasia or adenomatous colonic polyps that are not removed. Screening stool trial positive for enteric pathogens or Clostridium difficile toxin. Oral corticosteroids at a dose > 40 mg prednisone or its equivalent per day at inclusion (oral steroids should be at stable dose at least 7 days before inclusion) Any current or previous use of cyclosporine, tacrolimus, anti-TNF therapy, and other biologics (except vedolizumab), JAK inhibitors (approved or investigational), or any current or previous use of an investigational agent within 5 half-lives of that agent before the first trial agent injection. Contraindication to anti-TNF therapy according to drug labeling: Active infection. Non-treated latent tuberculosis. Heart failure (NYHA: Grade III and IV). Malignancy during the previous 5 years. Demyelinating neurological disease. Current or recent (less than 4 weeks) vaccination with attenuated live vaccines Patients with a dominant arm deficiency or physical impairment impeding the achievement of the tests Patients using a prohibited medication Patients participating in another trial or being in a follow-up period for another trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group Standard of care<br>In standard of care, patient only visits every 3 months the doctor so the optimization of treatment can be done only at this frequency. | Drug: Adalimumab<br>* Patients will all receive Adalimumab 160/80/40mg EOW until V1 (W14) followed by 40mg EOW until V2 (W26)<br>|
| Active Comparator: Groupe T2T with telemonitoring and patient education<br>Treatment with e-Monitoring, home fecal calprotectin testing and therapy education. | Drug: Adalimumab<br>* Patients will all receive Adalimumab 160/80/40mg EOW until V1 (W14) followed by 40mg EOW until V2 (W26)<br>Diagnostic Test: Calprotectin<br>* Fecal calprotectin dosing at home with IBDoc<br>Other: e-Monitoring<br>* e-Monitoring at Week 6, Week 10, Week 14, Week 18, Week 22, Week 26, Week 34, Week 38, Week 42 and Week 48 The patient must complete the first 2 questions of the Mayo score: Stool frequency The frequency of bleeding He must also complete the information on his injections<br>Other: Therapy Education<br>* Patient Education at W0, W2, W14, W26 and W38.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopic Remission | Treatment success of a treat to target with telemonitoring follow up using e-Monitoring and fecal calprotectin dosing at home associated to an appropriate patient education compared to standard treatment follow up at Week 48. Definition of treatment success: Endoscopic remission defined by an endoscopic Mayo score 0 | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of adalimumab treatment on clinical remission (at Week 48) | Remission without steroids: Remission rate and remission rate without steroids at study visits and Week 48 | Week 48 | 
| Efficacy of adalimumab treatment on endoscopic Healing (at Week 48) | Endoscopic healing rate with Mayo score 0 or 1 | Week 48 | 
| Efficacy of adalimumab treatment on endoscopic mucosal healing | UCEIS score | Week 48 | 
| Efficacy of adalimumab treatment on histological Healing (at Week 48) | Histological healing (Nancy index) | Week 48 | 
| Efficacy of adalimumab treatment on patient quality of life (at Week 48) | Quality of life evolution (evaluate visit 0 vs -Week 14, Week 26, Week 38 and Week 48) | Week 48 | 
| Patient satisfaction | Patient satisfaction evaluate with all questionnaires of quality of life | Week 48 | 
| Treatment compliance | Treatment compliance evaluate at every visit | Week 48 | 
| Patient adhesion | Patient adhesion evaluate with questionnaire | Week 48 | 
| Disability score evolution | IBD Disability index, evaluate visit 0 vs - Week 14, Week 26, Week 38 and Week 48 | Week 48 | 
| Medico-economic analysis | Medico-economic comparative analysis between standard of care follow up and tight monitoring follow up | Week 48 | 
| Continuous Clinical Response (CCR) | Definition: Partial Mayo Response at each visit (Visit 1, Visit 2, Visit 3) with a total Mayo response on Week 48 Visit 4 visit. In the telemonitoring group the partial Mayo limited to questions 1 and 2 will be directly answered by patients themselves through ePRO2 they will score the first 2 questions of partial Mayo from home and send that info to the investigator. | Week 48 | 
| Loss of clinical response | Pharmacokinetic dosage of Adalimumab (Anti-TNF) | Week 48 | 
| Number of visits in trial | Number of visits in trial per patients | Week 48 | 
| Colectomies at Week 48 | Proportion of patients with colectomy | Week 48 | 
| UC related Hospitalizations at Week 48 | Proportion of UC related hospitalizations | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBD, UC