High Dose Oral 4-Aminosalicylic Acid (PASER®) to Control Acute Flares of Mild to Moderate Crohn's Disease in Children

Study Overview
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Brief Summary
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The purpose of this 4 week study is to determine whether PASER®, an approved delayed-release oral formulation of 4-aminosalicylic acid, in doses of 50 milligrams per kilogram three times daily for 2 weeks followed by 50 milligrams per kilogram twice daily for 2 weeks, will resolve an acute flare of ileocecal Crohn's disease.

Detailed Description
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Eligible pediatric patients with acute flares of ileocecal Crohn's disease will be randomized to receive either PASER®, an approved delayed-release oral formulation of 4-aminosalicylic acid, in doses of 50 milligrams per kilogram three times daily for 2 weeks followed by 50 milligrams per kilogram twice daily for 2 weeks, or an identical-appearing placebo preparation. Patients will be required to maintain a daily diary and to return at 2 weeks for blood and stool tests. At the four week mark, patients will return for clinical evaluation, global assessment of disease activity and change in disease activity, as well as additional laboratory tests.

Official Title
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A Prospective Randomized Double-Blind Study of PASER® in the Management of Patients Experiencing an Acute Flare of Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: 4-Aminosalicylic acid extended release granules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age less than 18 years Crohn's disease predominantly involving the ileum and/or cecum. The diagnosis must have been established by radiography, endoscopy and/or biopsy (at least 2 of the 3 modalities) with at least one confirmatory test having been performed no more than 36 months before entry. The diagnosis must have been confirmed by at least one gastroenterologist. Harvey Bradshaw Index of at least 7 The onset of the acute flare should have been abrupt, declaring itself over 72 hours, and should have started no more than 4 weeks before study entry. Symptoms relating to the flare should not have diminished or started to improve prior to entry. Written informed consent Exclusion Criteria: Concomitant corticosteroids, budesonide Corticosteroids within 2 months Cyclosporine, mycophenolate mofetil or experimental drugs during the last three months Maintenance infliximab, or infliximab or other biologics in the preceding 3 months If the severity of the flare has started to decrease spontaneously Coexisting diagnosis of primary sclerosing cholangitis Infectious diarrhea Signs of intestinal obstruction or perforation New fistulization as part of the acute flare or increased activity in chronic fistula(e) as part of the acute flare Hypersensitivity to 4-ASA or any components of PASER® Pregnancy or breast-feeding Failure of a woman of child-bearing potential to agree to use adequate contraception for the 4 week period of the trial, if sexually active Severe renal or hepatic disease (i.e., more than 3 times upper limit of normal) or a WBC < 3,000 during the preceding three months

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>4-Aminosalicylic acid extended release granules (as volume equivalent of active product), 50 mg/kg orally three times daily for two weeks followed by (as volume equivalent) 50 mg/kg orally two times daily for 2 weeks | Drug: 4-Aminosalicylic acid extended release granules<br>* Granules for oral administration will be administered as a volume equivalent to 50 mg/kg of 4-aminosalicylic acid three times daily for 2 weeks followed by 2 times daily for 2 weeks in the active arm or a comparable volume in the placebo arm<br>* Other names: 4-ASA;|
| Placebo Comparator: Placebo<br>Placebo granules identical in appearance to the active arm (as volume equivalent of active product), 0 mg/kg orally three times daily for two weeks followed by (as volume equivalent) 0 mg/kg orally two times daily for 2 weeks | Drug: 4-Aminosalicylic acid extended release granules<br>* Granules for oral administration will be administered as a volume equivalent to 50 mg/kg of 4-aminosalicylic acid three times daily for 2 weeks followed by 2 times daily for 2 weeks in the active arm or a comparable volume in the placebo arm<br>* Other names: 4-ASA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in the Modified Crohn's Disease Activity Index (mCDAI) Score of >70 Points by 4 Weeks Compared With Baseline | Reduction in the Modified Crohn's Disease Activity Index (mCDAI) score of >70 points by 4 weeks after randomization compared with baseline | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Remission | Rate of remission was defined by a decrease in modified Crohn's Disease Activity Index (mCDAI) > 100 points and total mCDAI < 150 by 4 weeks | 4 weeks | 
| Rate of Response as Defined by a Reduction in HBI to Less Than 5 by 4 Weeks |  | 4 weeks | 
| Rate of Remission as Defined by the Decrease in HBI to Less Than 3 by 4 Weeks |  | 4 weeks | 
| Time to Response and/or Remission Including Time to Change in HBI, According to Elements of the Daily Patient Diary |  | up to 4 weeks | 
| Rate of Response as Defined by the Decrease in PCDAI of 12.5 Points by 4 Weeks |  | 4 weeks | 
| Rate of Remission as Defined by the Decrease in PCDAI < 10 by 4 Weeks |  | 4 weeks | 
| Change in IMPACT-III From Baseline to 4 Weeks |  | 4 weeks | 
| Change From Baseline in the Patient's General Sense of Disease Activity as Recorded in the Individual Daily Diary |  | 4 weeks | 
| Absence of Night Time Stools, if They Were Present on Entry, and Time to Disappearance |  | up to 4 weeks | 
| Time to Normalization of All Other Components in the Diary |  | up to 4 weeks | 
| Change in Hgb, ESR, CRP, Platelet Count, Calprotectin From Baseline and Time to Normalization |  | 2 weeks and 4 weeks | 
| Change in Global Physician Assessment of Disease Activity From Baseline to Study Completion |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's, Crohn's Disease, Acute Flare, Mild to Moderate Crohn's Disease, Children, Pediatrics, Ileo-cecal, Pediatric Crohn's Disease, New Onset Crohn's Disease, Recently diagnosed Crohn's Disease