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

Phase 2

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	4-Aminosalicylic acid extended release granules	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
Active	4-Aminosalicylic acid extended release granules	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

Primary Outcome Measures

Name	Time	Method
Reduction in the Modified Crohn's Disease Activity Index (mCDAI) Score of >70 Points by 4 Weeks Compared With Baseline	4 weeks	Reduction in the Modified Crohn's Disease Activity Index (mCDAI) score of \>70 points by 4 weeks after randomization compared with baseline

Secondary Outcome Measures

Name	Time	Method
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 PCDAI < 10 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 Remission	4 weeks	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
Change in Global Physician Assessment of Disease Activity From Baseline to Study Completion	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
Rate of Response as Defined by the Decrease in PCDAI of 12.5 Points by 4 Weeks	4 weeks
Change in Hgb, ESR, CRP, Platelet Count, Calprotectin From Baseline and Time to Normalization	2 weeks and 4 weeks

Locations (5): University of California, San Francisco
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San Francisco, California, United States
Atlantic Health System / Morristown Memorial Hospital / Goryeb Children's Hospital
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Morristown, New Jersey, United States
Cedars-Sinai Medical Center
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Los Angeles, California, United States
Children's Center for Digestive HealthCare, LLC
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Atlanta, Georgia, United States
Texas Children's Hospital, Baylor College of Medicine
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Houston, Texas, United States