Clinical trial NCT00495521: High Dose Oral 4-Aminosalicylic Acid (PASER®) to Control Acute Flares of Mild to Moderate Crohn's Disease in Children
Official title: A Prospective Randomized Double-Blind Study of PASER® in the Management of Patients Experiencing an Acute Flare of Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: 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
Lead sponsor: Jacobus Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2007-07-03
Enrollment: 2
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Reduction in the Modified Crohn's Disease Activity Index (mCDAI) Score of >70 Points by 4 Weeks Compared With Baseline
timeFrame: 4 weeks
Secondary outcomes:
measure: Rate of Remission
timeFrame: 4 weeks
measure: Rate of Response as Defined by a Reduction in HBI to Less Than 5 by 4 Weeks
timeFrame: 4 weeks
measure: Rate of Remission as Defined by the Decrease in HBI to Less Than 3 by 4 Weeks
timeFrame: 4 weeks
measure: Time to Response and/or Remission Including Time to Change in HBI, According to Elements of the Daily Patient Diary
timeFrame: up to 4 weeks
measure: Rate of Response as Defined by the Decrease in PCDAI of 12.5 Points by 4 Weeks
timeFrame: 4 weeks
measure: Rate of Remission as Defined by the Decrease in PCDAI < 10 by 4 Weeks
timeFrame: 4 weeks
measure: Change in IMPACT-III From Baseline to 4 Weeks
timeFrame: 4 weeks
measure: Change From Baseline in the Patient's General Sense of Disease Activity as Recorded in the Individual Daily Diary
timeFrame: 4 weeks
measure: Absence of Night Time Stools, if They Were Present on Entry, and Time to Disappearance
timeFrame: up to 4 weeks
measure: Time to Normalization of All Other Components in the Diary
timeFrame: up to 4 weeks
measure: Change in Hgb, ESR, CRP, Platelet Count, Calprotectin From Baseline and Time to Normalization
timeFrame: 2 weeks and 4 weeks
measure: Change in Global Physician Assessment of Disease Activity From Baseline to Study Completion
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Atlanta
country: United States
facility: Children's Center for Digestive HealthCare, LLC
state: Georgia
city: Morristown
country: United States
facility: Atlantic Health System / Morristown Memorial Hospital / Goryeb Children's Hospital
state: New Jersey
city: Houston
country: United States
facility: Texas Children's Hospital, Baylor College of Medicine
state: Texas
Study officials:
affiliation: Jacobus Pharmaceutical
name: David P Jacobus, MD
role: STUDY_CHAIR
affiliation: Jacobus Pharmaceutical
name: Kathy L Ales, MD
role: STUDY_DIRECTOR
affiliation: Texas Children's Hospital, Baylor College of Medicine
name: George D Ferry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Medical Center
name: Marla C Dubinsky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Atlantic Health System, Morristown General Hospital, Goryeb Children's Hospital
name: Joel R Rosh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Melvin B. Heyman, M.D., M.P.H.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Center for Digestive Healthcare, LLC
name: Stanley A. Cohen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: