Crohn´s Disease
Conditions
Brief summary
The purpose of this trial is to demonstrate that Pentasa administered as a 2 g morning dose and a 4 g evening dose is efficacious in active mild to moderate CD.
Interventions
DRUGPentasa
6 g/day orally, 2 g in the morning and 4 g in the evening
DRUGPlacebo
6 g/day orally, 2 g in the morning and 4 g in the evening
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(main): * Age: at least 18 years * CD symptoms/onset of disease: ≥ 3 months prior to Visit 1 * Ileal, ileo-colonic or colonic non-stricturing/non-penetrating disease * A confirmed location of CD (by MRI, X-ray (small bowel and/or colon), and/or endoscopy) * A Harvey-Bradshaw score between 5 and 12 * Males and non-pregnant, non-nursing women * Mild to moderate active CD, defined by a CDAI score between 180 and 350 * Active inflammatory disease (C-Reactive Protein (CRP) level above or equal to 5 mg/L), or a biopsy verified inflammation, or fecal calprotectin level above or equal to 50 µg/g) * Estimated creatinine clearance should be above 75 ml/min
Exclusion criteria
(main): * Any significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the trial, or may influence the results of the trial or the patient's ability to participate in the trial * CD located to the upper gastrointestinal tract and/or jejunal part of the small intestine, and/or to colon below the left colon flexure and/or isolated proctitis and/or anal disease * Prior treatment resistance to Pentasa (mesalazine) * Chronic, dominant arthralgia or rheumatoid arthritis * Palpable abdominal mass * Biologics (eg anti-TNF-α) must not be used during the trial or 6 months before Visit 1 * Continuous usage of systemic steroids (excluding budesonide) for 3 months or more within the past year * Positive pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Crohn's Disease Activity Index (CDAI) Responders at Week 10. | At Week 10, end of treatment | The Crohn's Disease Activity Index (CDAI) is a composite score to quantify symptoms of Crohn's disease. It has a range of 0-600; higher scores are worse. A responder is defined as a participant who achieved a reduction in the CDAI score to \<150 or a decrease in CDAI score of at least 70. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline to Week 10 in Fecal Calprotectin | At Week 10, end of treatment | Fecal calprotectin is an inflammatory marker for the gastrointestinal tract. Higher values indicate more serious inflammation. |
| Relative Change From Baseline to Each Visit in Serum C-reactive Protein (CRP) | Within the 10 week treatment period | Serum CRP is a laboratory measure of acute inflammation. Higher values are worse. |
| Relative Change From Baseline to Each Visit in Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Within the 10 week treatment period | The IBDQ is a measure of the impact of inflammatory bowel disease (IBD) on health-related quality-of-life (HRQL; mood, social activities, daily life, and IBD-related health worries). Higher scores are better; Total IBDQ score can range from 32 (very poor HRQL) to 224 (perfect HRQL). |
| Relative Change From Baseline to Each Visit in Work Productivity & Activity Impairment Questionnaire (WPAI_CD) Score Item 5 (Work Productivity) | Within the 10 week treatment period | The WPAI\_CD Item 5 measures the impact of Crohn's disease on work productivity (while working). The score is recorded by the patient on a visual analog scale, from 0 to 10. Lower scores are better, while higher scores indicate greater negative effect on work productivity. |
| Relative Change From Baseline to Week 10 in Estimated Creatinine Clearance | At Week 10, end of treatment | A lower creatinine clearance indicates worsening of renal function. Creatinine clearance was estimated from serum creatinine levels, using the Cockcroft-Gault formula. |
Countries
Belgium, Denmark, France, Germany, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mesalazine Mesalazine (Mesalamine) 2 g sachet; 6 g daily | 7 |
| Placebo Placebo to Mesalazine (Mesalamine) 2 g sachet; 6 g daily | 11 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Exclusion criterion violation | 0 | 1 |
| Overall Study | Incorrect randomisation | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Mesalazine | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 7 Participants | 11 Participants |
| Age Continuous | 37.5 years STANDARD_DEVIATION 12.4 | 37.6 years STANDARD_DEVIATION 13.2 | 37.5 years STANDARD_DEVIATION 12.6 |
| Region of Enrollment Belgium | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Denmark | 1 participants | 0 participants | 1 participants |
| Region of Enrollment France | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Germany | 6 participants | 4 participants | 2 participants |
| Region of Enrollment Sweden | 1 participants | 1 participants | 0 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 9 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 14 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 8 | 7 / 11 |
| serious Total, serious adverse events | 0 / 8 | 0 / 11 |
Outcome results
Primary
Percentage of Crohn's Disease Activity Index (CDAI) Responders at Week 10.
The Crohn's Disease Activity Index (CDAI) is a composite score to quantify symptoms of Crohn's disease. It has a range of 0-600; higher scores are worse. A responder is defined as a participant who achieved a reduction in the CDAI score to \<150 or a decrease in CDAI score of at least 70.
Time frame: At Week 10, end of treatment
Population: The percentage of CDAI responders at Week 10 was analysed for the FAS (treated participants with post-baseline CDAI), Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesalazine | Percentage of Crohn's Disease Activity Index (CDAI) Responders at Week 10. | 43 percentage of participants |
| Placebo | Percentage of Crohn's Disease Activity Index (CDAI) Responders at Week 10. | 55 percentage of participants |
Comparison: The odds ratio (OR) for Baseline CDAI measures the effect of an increase of one unit on the outcome. The OR \[95% CI\] and p-value (likelihood-based) are for Pentasa versus placebo estimated in a logistic regression analysis including TREATMENT and CDAI at baseline as covariates. Power to demonstrate superiority of PENTASA Sachet 6 g/day over placebo in the primary efficacy analysis was 90% for a planned sample size of 255 participants per treatment arm (assuming 10% nonassessable participants).p-value: 0.23195% CI: [0.017, 2.683]Regression, Logistic
Secondary
Relative Change From Baseline to Each Visit in Inflammatory Bowel Disease Questionnaire (IBDQ) Score
The IBDQ is a measure of the impact of inflammatory bowel disease (IBD) on health-related quality-of-life (HRQL; mood, social activities, daily life, and IBD-related health worries). Higher scores are better; Total IBDQ score can range from 32 (very poor HRQL) to 224 (perfect HRQL).
Time frame: Within the 10 week treatment period
Population: Full Analysis Set (OC). Descriptive statistics only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalazine | Relative Change From Baseline to Each Visit in Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Baseline | 138.57 IBDQ score | Standard Deviation 32.07 |
| Mesalazine | Relative Change From Baseline to Each Visit in Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 10 | 164 IBDQ score | Standard Deviation 24.99 |
| Placebo | Relative Change From Baseline to Each Visit in Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Baseline | 130.27 IBDQ score | Standard Deviation 29.32 |
| Placebo | Relative Change From Baseline to Each Visit in Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Week 10 | 121.88 IBDQ score | Standard Deviation 39.96 |
Secondary
Relative Change From Baseline to Each Visit in Serum C-reactive Protein (CRP)
Serum CRP is a laboratory measure of acute inflammation. Higher values are worse.
Time frame: Within the 10 week treatment period
Population: Full Analysis Set (OC). Descriptive statistics only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalazine | Relative Change From Baseline to Each Visit in Serum C-reactive Protein (CRP) | Baseline | 8.23 mg/L | Standard Deviation 5.71 |
| Mesalazine | Relative Change From Baseline to Each Visit in Serum C-reactive Protein (CRP) | Week 10 | 7.76 mg/L | Standard Deviation 6 |
| Placebo | Relative Change From Baseline to Each Visit in Serum C-reactive Protein (CRP) | Baseline | 10.25 mg/L | Standard Deviation 6.96 |
| Placebo | Relative Change From Baseline to Each Visit in Serum C-reactive Protein (CRP) | Week 10 | 9.48 mg/L | Standard Deviation 8.41 |
Secondary
Relative Change From Baseline to Each Visit in Work Productivity & Activity Impairment Questionnaire (WPAI_CD) Score Item 5 (Work Productivity)
The WPAI\_CD Item 5 measures the impact of Crohn's disease on work productivity (while working). The score is recorded by the patient on a visual analog scale, from 0 to 10. Lower scores are better, while higher scores indicate greater negative effect on work productivity.
Time frame: Within the 10 week treatment period
Population: Full Analysis Set (OC). Descriptive statistics only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalazine | Relative Change From Baseline to Each Visit in Work Productivity & Activity Impairment Questionnaire (WPAI_CD) Score Item 5 (Work Productivity) | Baseline | 4.17 WPAI_CD Item 5 score | Standard Deviation 3.25 |
| Mesalazine | Relative Change From Baseline to Each Visit in Work Productivity & Activity Impairment Questionnaire (WPAI_CD) Score Item 5 (Work Productivity) | Week 10 | 1.83 WPAI_CD Item 5 score | Standard Deviation 1.47 |
| Placebo | Relative Change From Baseline to Each Visit in Work Productivity & Activity Impairment Questionnaire (WPAI_CD) Score Item 5 (Work Productivity) | Baseline | 5 WPAI_CD Item 5 score | Standard Deviation 2.33 |
| Placebo | Relative Change From Baseline to Each Visit in Work Productivity & Activity Impairment Questionnaire (WPAI_CD) Score Item 5 (Work Productivity) | Week 10 | 4.4 WPAI_CD Item 5 score | Standard Deviation 2.07 |
Secondary
Relative Change From Baseline to Week 10 in Estimated Creatinine Clearance
A lower creatinine clearance indicates worsening of renal function. Creatinine clearance was estimated from serum creatinine levels, using the Cockcroft-Gault formula.
Time frame: At Week 10, end of treatment
Population: Safety Analysis Set (OC). Descriptive statistics only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalazine | Relative Change From Baseline to Week 10 in Estimated Creatinine Clearance | Baseline | 122.63 mL/min | Standard Deviation 26.91 |
| Mesalazine | Relative Change From Baseline to Week 10 in Estimated Creatinine Clearance | Week 10 | 124 mL/min | Standard Deviation 32.14 |
| Placebo | Relative Change From Baseline to Week 10 in Estimated Creatinine Clearance | Baseline | 102.55 mL/min | Standard Deviation 24.13 |
| Placebo | Relative Change From Baseline to Week 10 in Estimated Creatinine Clearance | Week 10 | 105.11 mL/min | Standard Deviation 31.09 |
Secondary
Relative Change From Baseline to Week 10 in Fecal Calprotectin
Fecal calprotectin is an inflammatory marker for the gastrointestinal tract. Higher values indicate more serious inflammation.
Time frame: At Week 10, end of treatment
Population: Full Analysis Set (FAS), observed cases (OC), descriptive statistics only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mesalazine | Relative Change From Baseline to Week 10 in Fecal Calprotectin | Baseline | 244.5 microgram/gram faeces | Standard Deviation 212.09 |
| Mesalazine | Relative Change From Baseline to Week 10 in Fecal Calprotectin | Week 10 | 181.57 microgram/gram faeces | Standard Deviation 216.15 |
| Placebo | Relative Change From Baseline to Week 10 in Fecal Calprotectin | Baseline | 362 microgram/gram faeces | Standard Deviation 311.57 |
| Placebo | Relative Change From Baseline to Week 10 in Fecal Calprotectin | Week 10 | 1180.17 microgram/gram faeces | Standard Deviation 2295.34 |