Efficacy and Safety of Two Regimens of Maintenance Therapy in Children With Crohn Disease

Phase 3

• Conditions: Crohn Disease
• Interventions: Drug: Infliximab with azathioprine (IIFX + AZA); Drug: Infliximab (IFX alone)

• Registration Number: NCT01559142
• Lead Sponsor: Children's Memorial Health Institute, Poland

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:

1. Infliximab with immunomodulation

2. 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:

1. Infliximab with immunomodulation

2. 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

Study Timeline

• Study Start: 2008-11
• Study First Submitted: 2012-03-19
• Study First Submitted QC: 2012-03-20
• Study First Posted: 2012-03-21
• Status Verified: 2012-04
• Primary Completion: 2012-04
• Last Update Submitted: 2012-04-02
• Last Update Posted: 2012-04-04
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. 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.
2. Efficient methods of contraception in patients of childbearing potential during study period and six months after.
3. Patients will be enrolled to Part B of the study whether they finish Part A with clinical remission or clinical response.

Exclusion Criteria

1. Hypersensitivity to infliximab
2. Pregnancy and breastfeeding
3. Active tuberculosis or other severe infection: sepsis, opportunistic infections, active CMV, yersinia pseudotuberculosis, pneumocystis carini, atypical mycobacteriosis
4. VZV infection, hepatitis, pneumonia during 3 months before Day 0 of the study
5. pancytopaenia and aplastic anemia
6. moderate and severe heart insufficiency (NYHA class III/IV), or unstable coronary heart disease
7. chronic pulmonary insufficiency, chronic renal insufficiency, chronic liver insufficiency
8. HIV infection
9. Presence of severe diseases of nervous system or severe endocrinological, hematological, psychiatric diseases.
10. Demyelinisation syndrome or symptoms resembling Demyelinisation syndrome
11. Malignancy or premalignant conditions during 5 years before Day 0 of the study.
12. Severe infection currently present
13. Malignancy currently present

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IFX TG	Infliximab with azathioprine (IIFX + AZA)	-
IFX alone	Infliximab (IFX alone)	-

Primary Outcome Measures

Name	Time	Method
Clinical disease activity	14 week and one year

Secondary Outcome Measures

Name	Time	Method
endoscopic disease activity	14 week and one year

Trial Locations

Locations (1)

Department of Gastroenterology, Hepatology and Feeding Disorders; 🇵🇱 Warsaw, Poland