Two Therapeutic Strategies for the Maintenance of Remission in Patients With Ulcerative Colitis (SCILLA)

Comparison Between Two Therapeutic Strategies for the Maintenance of Clinical and Endoscopic Remission in Patients With Ulcerative Colitis Treated by Infliximab

Ulcerative colitis patients treated with Infliximab (IFX) in deep remission after at least 12 months of treatment will be randomized to continue IFX or to stop IFX and start Azathioprine (AZA).

Each patient will be followed for 12 months.

Study Overview

• Status: Unknown
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Azathioprine; Drug: Infliximab

Detailed Description

All eligible subjects will be able to participate in the study at any infusion occurred after 12 months since the beginning. They will be screened by medical history, physical examination, blood and faecal tests (included C-reactive protein and faecal calprotectin), as required by clinical practice. No children, pregnant or breastfeeding women, or elder subjects will be included. A colonoscopy + biopsies in the area of greater inflammation will be performed within ± 3 weeks since the baseline visit. The subjects can then be randomized and receive their first dose of study medication.

Subjects will be then evaluated every 8 weeks for the following 12 months from the randomization. Clinical and blood tests will be performed, and the partial Mayo Score will be calculated at each visit, until the final visit, when a new colonoscopy with biopsies will be repeated and the global Mayo Score will be evaluated. At final visit a new faecal sample for calprotectin will be collected.

Safety of the study treatments will be evaluated at each study visit. In case of study agent discontinuation, the patient will be managed according to usual practice and followed for the entire study period. Patients randomized in AZA arm, could restart IFX.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Silvio Danese, MD, PhD; Phone Number: +390282245555; Email: IBDclinicaltrials@humanitas.it
• Study Contact Backup: Name: Gionata Fiorino, MD, PhD; Phone Number: +390282245555; Email: daniela.gilardi@humanitas.it

Study Locations

• Italy
  • MI
    • Rozzano, MI, Italy, 20089
      • Recruiting
      • IBD Center
      • Contact: Silvio Danese, MD, PhD; Phone Number: 5555 0039028224; Email: IBDclinicaltrials@humanitas.it
      • Contact: Gionata Fiorino, MD, PhD; Phone Number: 5555 0039028224; Email: gionata.fiorino@humanitas.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 -65 years
• Written informed consent and willing to adhere to study procedures.
• Therapy with infliximab since at least 12 months, with one infusion every 8 weeks (a maximum interval between two infusions of ± 3 weeks is allowed)
• Sustained steroid-free remission in the last 6 months prior to inclusion, except for use of steroids as a preventive measure for infliximab infusion reaction, if required by local guidelines.
• Global Mayo score at baseline ≤ 2
• All Mayo subscores ≤ 1
• Absence of rectal bleeding
• Effective methods to avoid pregnancy during the study period

Exclusion Criteria:

• Disabling and persisting extraintestinal manifestation at baseline
• Patients unable to comply with study procedures
• Known intolerance or previous allergic reaction to thiopurines
• Concomitant therapy with allopurinol
• Any disease not compatible with the use of infliximab or azathioprine, as per clinician's judgement.
• Need for dose escalation of infliximab in the last 12 months prior to baseline.
• White blood cell count < 3000/mmc or absolute clinically relevant lymphopenia at baseline
• Active pregnancy or breastfeeding; willing for pregnancy during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Azathioprine; Azathioprine 2-2.5 mg/kg/day, according to approved indication	Drug: Azathioprine; AZA treatment after IFX withdrawal for maintenance of remission
ACTIVE_COMPARATOR: Infliximab; Infliximab 5 mg/kg every 8 weeks	Drug: Infliximab; IFX treatment for maintenance of remission

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse rate	relapse rate in the two study groups.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse time	Mean time to relapse in the two groups	12 months
Number of adverse events [Safety and Tolerability]	Number of adverse events of the two study strategies	12 months
Number of serious adverse events [Safety and Tolerability]	Number of serious adverse events of the two study strategies	12 months
Identification of potential risk factors for relapse. Age, sex, smoking habits, histological healing of mucosa and each Mayo subscore at baseline will be examined	Potential risk factor for relapse will be evaluated by univariable analysis, and a multivariable analysis will be performed for all factors with p<0.30. Risk factors will be also analysed by logistic regression. Analysis of predetermined baseline characteristics (age, sex, smoking habits, histological healing of mucosa at baseline, and each Mayo subscore (stool number, presence of blood, colonic ulcerations) excluding the physician global assessment) to identify predictive factors for relapse.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Direct costs [Pharmacokinetics]	Direct costs of the two treatment strategies	12 months

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas
• Collaborators: Agenzia Italiana del Farmaco

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2017
• Primary Completion (ANTICIPATED): October 3, 2019
• Study Completion (ANTICIPATED): April 3, 2020

Study Registration Dates

• First Submitted: May 8, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (ACTUAL): May 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 10, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Infliximab; Azathioprine
• Other Study ID Numbers: 1685

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No