Intensive Treatment to Reach the Target With Golimumab in ulcErative coliTis - In-TARGET

• Status: Active, not recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
• Treatments: Antibodies, Monoclonal; Golimumab

Criteria

INCLUSION CRITERIA

• Age sup 18 years and inf 75 years

• Established diagnosis of UC for at least 3 months (pancolitis, left-sided colitis, proctosigmoiditis and or proctitis are allowed).

• Adults with moderately-to-severely active UC who had an inadequate response to or failed to tolerate steroids AND thiopurines (azathioprine or 6-mercaptopurine) or adults with moderately-to-severely active UC who had no response to an adequate steroid course and starting golimumab.

• Active disease at golimumab treatment initiation defined as a partial MAYO score sup/equal 6 with an endoscopic sub score sup/equal 2.

• Patients concurrently treated with oral corticosteroids will receive a stable dose (prednisone 20 ≤mg/day for at least 2 weeks) before baseline.

• Patient has to be treated with oral 5-ASA at time of inclusion regardless of the dose if no contra-indication. If the patient is not on oral 5-ASA during the screening period, he/she should start mesalamine at 2g per day or asacol at 1.6 g per day, in the absence of contra-indication.

• Patients are allowed stable dose of thiopurines (azathioprine or 6-mercaptopurine stable dose for at least 4 weeks).

• Naïve to anti-TNF therapy, and other biologics, including anti-integrin antibodies and for all biologics known to be effective for UC (approved or investigational).

• Naïve to JAK inhibitors (approved or investigational)

• A contraceptive method during the whole study for childbearing potential female patients.

EXCLUSION CRITERIA

• Age under 18 and over 75.

• People 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 study positive for enteric pathogens or Clostridium difficile toxin.

• Oral corticosteroids at a dose > 20 mg prednisone or its equivalent per day.

• Any current or previous use of cyclosporine, tacrolimus, anti-TNF therapy, and other biologics, including anti-integrin antibodies (approved or investigational), 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 study agent injection.

• Contraindication to anti-TNF therapy according to drug labelling:

• Active infection.

• Non-treated latent tuberculosis.

• Heart failure (NYHA: Grade III and IV).

• Malignancy during the previous 5 years.

• Demyelinating neurological disease.

• Should be vaccinated with attenuated live vaccines