Crohn's Disease
Conditions
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
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.
Interventions
DRUG4-Aminosalicylic acid extended release granules
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
Sponsors
Jacobus Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 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 | — |
| Change in IMPACT-III From Baseline to 4 Weeks | 4 weeks | — |
Countries
United States
Participant flow
Recruitment details
The study was open to eligible patients under the care of or referred to investigators at 5 different academic medical centers from July 2007 through October 2008.
Pre-assignment details
Recruitment was slow with only 2 patients entered.
Participants by arm
| Arm | Count |
|---|---|
| 4-Aminosalicylic Acid Extended Release Granules Oral granules administered as (volume equivalent of active product) 50 mg/kg three times daily for two weeks followed by (volume equivalent) 50 mg/kg two times daily for 2 weeks | 1 |
| Placebo Granules Oral granules administered as (volume equivalent of active product) 0 mg/kg three times daily for two weeks followed by (volume equivalent) 0 mg/kg two times daily for 2 weeks | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | 4-Aminosalicylic Acid Extended Release Granules | Placebo Granules | Total |
|---|---|---|---|
| Age, Continuous | 12 years | 14 years | 13 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
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
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Reduction in the Modified Crohn's Disease Activity Index (mCDAI) Score of >70 Points by 4 Weeks Compared With Baseline | 1 participants |
| Placebo | Reduction in the Modified Crohn's Disease Activity Index (mCDAI) Score of >70 Points by 4 Weeks Compared With Baseline | 1 participants |
Secondary
Absence of Night Time Stools, if They Were Present on Entry, and Time to Disappearance
Time frame: up to 4 weeks
Secondary
Change From Baseline in the Patient's General Sense of Disease Activity as Recorded in the Individual Daily Diary
Time frame: 4 weeks
Secondary
Change in Global Physician Assessment of Disease Activity From Baseline to Study Completion
Time frame: 4 weeks
Secondary
Change in Hgb, ESR, CRP, Platelet Count, Calprotectin From Baseline and Time to Normalization
Time frame: 2 weeks and 4 weeks
Secondary
Change in IMPACT-III From Baseline to 4 Weeks
Time frame: 4 weeks
Secondary
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
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Rate of Remission | 1 Participants |
| Placebo | Rate of Remission | 1 Participants |
Secondary
Rate of Remission as Defined by the Decrease in HBI to Less Than 3 by 4 Weeks
Time frame: 4 weeks
Secondary
Rate of Remission as Defined by the Decrease in PCDAI < 10 by 4 Weeks
Time frame: 4 weeks
Secondary
Rate of Response as Defined by a Reduction in HBI to Less Than 5 by 4 Weeks
Time frame: 4 weeks
Secondary
Rate of Response as Defined by the Decrease in PCDAI of 12.5 Points by 4 Weeks
Time frame: 4 weeks
Secondary
Time to Normalization of All Other Components in the Diary
Time frame: up to 4 weeks
Secondary
Time to Response and/or Remission Including Time to Change in HBI, According to Elements of the Daily Patient Diary
Time frame: up to 4 weeks