Efficacy and Safety of Two Regimens of Maintenance Therapy in Children With Crohn Disease
Primary Purpose
Crohn Disease
Status
Unknown status
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Infliximab with azathioprine (IIFX + AZA)
Infliximab (IFX alone)
Sponsored by
About this trial
This is an interventional treatment trial for Crohn Disease focused on measuring Crohn Disease, infliximab, azathioprine
Eligibility Criteria
Inclusion Criteria:
- Patients with severe Crohn disease (PCDAI in anamnesis more than 51 points), with PCDAI currently over 30 points, with no or loss of response for previous therapy (except biological agents). Patients may have active fistulas.
- Efficient methods of contraception in patients of childbearing potential during study period and six months after.
- Patients will be enrolled to Part B of the study whether they finish Part A with clinical remission or clinical response.
Exclusion Criteria:
- Hypersensitivity to infliximab
- Pregnancy and breastfeeding
- Active tuberculosis or other severe infection: sepsis, opportunistic infections, active CMV, yersinia pseudotuberculosis, pneumocystis carini, atypical mycobacteriosis
- VZV infection, hepatitis, pneumonia during 3 months before Day 0 of the study
- pancytopaenia and aplastic anemia
- moderate and severe heart insufficiency (NYHA class III/IV), or unstable coronary heart disease
- chronic pulmonary insufficiency, chronic renal insufficiency, chronic liver insufficiency
- HIV infection
- Presence of severe diseases of nervous system or severe endocrinological, hematological, psychiatric diseases.
- Demyelinisation syndrome or symptoms resembling Demyelinisation syndrome
- Malignancy or premalignant conditions during 5 years before Day 0 of the study.
- Severe infection currently present
- Malignancy currently present
Sites / Locations
- Department of Gastroenterology, Hepatology and Feeding Disorders
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
IFX TG
IFX alone
Arm Description
Outcomes
Primary Outcome Measures
Clinical disease activity
Secondary Outcome Measures
endoscopic disease activity
Full Information
NCT ID
NCT01559142
First Posted
March 19, 2012
Last Updated
April 2, 2012
Sponsor
Children's Memorial Health Institute, Poland
1. Study Identification
Unique Protocol Identification Number
NCT01559142
Brief Title
Efficacy and Safety of Two Regimens of Maintenance Therapy in Children With Crohn Disease
Official Title
Efficacy and Safety of Induction Therapy With Three Doses of Infliximab in Patients With Crohn Disease Aged 7-17 Years-multicenter Open Study. Efficacy and Safety of Two Regimens of Maintenance Therapy in Patients With Crohn Disease Aged 7-17 Years-multicenter Randomized Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Unknown status
Study Start Date
November 2008 (undefined)
Primary Completion Date
April 2012 (Anticipated)
Study Completion Date
December 2012 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Memorial Health Institute, Poland
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of the study is confirmation of efficacy of induction therapy with three doses of infliximab In patients with Crohn disease aged 7-17 years, and comparison of efficacy and safety of two regiment of maintenance therapy:
Infliximab with immunomodulation
Infliximab alone
Detailed Description
Study project Screening (Days -14 do 0): Laboratory and endoscopic (up to three months before Day 0) results will be obtained to check with inclusion/exclusion criteria.
Part A (Days 1 to 71): Induction therapy with 3 doses of infliximab 5 mg/kg will be applied on days 1 - 15 - 43. Simultaneously in patients receiving steroids, steroid tapering will be performed up to 71 Day. At Day 71 clinical (PCDAI) and endoscopic assessment will be done. Patients with no clinical response will be qualified to Follow-up surveillance group. Patients with clinical response present will be randomized to two groups of maintenance therapy:
1. Infliximab with immunomodulation 2. Infliximab alone
Part B (Weeks 10 - 54): Patient with both groups will have scheduled visits at Weeks 14, 22, 30, 38, 46. Infliximab infusions and laboratory tests will be performed at each visit. At Week 54 clinical (PCDAI) and endoscopic assessment will be done.
Follow Up: 4 weeks after last visit - SAE monitoring Aim of the study
The aim of the study is confirmation of efficacy of induction therapy with three doses of infliximab In patients with Crohn disease aged 7-17 years, and comparison of efficacy and safety of two regiment of maintenance therapy:
Infliximab with immunomodulation
Infliximab alone Drug dosing in therapy regimens.
Infliximab: 5 mg/kg mc In intravenous infusion lasting over 2 hrs. Azathioprine: 1,5 - 3 mg/kg/24h Methotrexate: 10 - 25 mg/week
Safety assessment
AE and SAE monitoring will be conducted during whole period of the study
Efficacy assessment
Primary endpoint
Part A:
• Clinical response defined as: Decrease of PCDAI ≥ 15 points AND PCDAI less than 30 points
• Remission defined as: PCDAI ≤ 10 points
Part B:
Loss of clinical response defined as:
Increase of PCDAI more than 15 points OR PCDAI > 30 points
Secondary endpoints
Part A:
• Time to steroid cessation
Part B:
• Necessity to increase/change maintenance therapy with
o Surgery
o Increase of infliximab dose
Increase of immunomodulator dose
Steroids induction
Statistical methods
ITT analysis
Primary endpoints: chi2 tests, Kaplan-Meier analysis
Secondary endpoints: chi2 tests, Kaplan-Meier analysis, U Mann-Whitney analysis
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease
Keywords
Crohn Disease, infliximab, azathioprine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IFX TG
Arm Type
Active Comparator
Arm Title
IFX alone
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Infliximab with azathioprine (IIFX + AZA)
Intervention Description
Infliximab with azathioprine during whole one year study
Intervention Type
Drug
Intervention Name(s)
Infliximab (IFX alone)
Intervention Description
Infliximab continuously; azathioprine stopped in 26 week
Primary Outcome Measure Information:
Title
Clinical disease activity
Time Frame
14 week and one year
Secondary Outcome Measure Information:
Title
endoscopic disease activity
Time Frame
14 week and one year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with severe Crohn disease (PCDAI in anamnesis more than 51 points), with PCDAI currently over 30 points, with no or loss of response for previous therapy (except biological agents). Patients may have active fistulas.
Efficient methods of contraception in patients of childbearing potential during study period and six months after.
Patients will be enrolled to Part B of the study whether they finish Part A with clinical remission or clinical response.
Exclusion Criteria:
Hypersensitivity to infliximab
Pregnancy and breastfeeding
Active tuberculosis or other severe infection: sepsis, opportunistic infections, active CMV, yersinia pseudotuberculosis, pneumocystis carini, atypical mycobacteriosis
VZV infection, hepatitis, pneumonia during 3 months before Day 0 of the study
pancytopaenia and aplastic anemia
moderate and severe heart insufficiency (NYHA class III/IV), or unstable coronary heart disease
chronic pulmonary insufficiency, chronic renal insufficiency, chronic liver insufficiency
HIV infection
Presence of severe diseases of nervous system or severe endocrinological, hematological, psychiatric diseases.
Demyelinisation syndrome or symptoms resembling Demyelinisation syndrome
Malignancy or premalignant conditions during 5 years before Day 0 of the study.
Severe infection currently present
Malignancy currently present
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaroslaw Kierkus, MD PhD
Organizational Affiliation
The Children's Memorial Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Gastroenterology, Hepatology and Feeding Disorders
City
Warsaw
ZIP/Postal Code
04-730
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Two Regimens of Maintenance Therapy in Children With Crohn Disease
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