Ulcerative Colitis
Conditions
Keywords
Moderately to severely active Ulcerative Colitis
Brief summary
Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active ulcerative colitis.
Detailed description
Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active UC.
Interventions
DRUGMTX 12.5
once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or \>9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab
DRUGMTX 25
once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or \>9). Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab
DRUGAdalimumab
Subjects will receive 18 weekly doses of adalimumab
Sponsors
Abbott
Alimentiv Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal \[defined as a minimum of one year since the last menstrual period\]). * Diagnosis of UC confirmed by established criteria, regardless of disease duration. * Moderate to severely active UC, defined by a modified Mayo Score ≥6, with confirmed endoscopic activity by central reader (Mayo endoscopic subscore ≥2). * Require initiation with adalimumab for induction of remission. * Ability of subject to swallow study drug capsules. * Ability of subject to participate fully in all aspects of this clinical trial. * Written informed consent must be obtained and documented.
Exclusion criteria
* Prior treatment with a TNF antagonist or biological therapy. * Prior treatment with MTX. * Disease limited to the rectum (proctitis). * Documented presence of antibodies against adalimumab. * Contraindication for anti-TNF or MTX therapy. * Contraindication for endoscopy. * Ostomy. * Planned surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups | Baseline up to Week 18 | The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups. | Baseline up to Week 18 | UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration). The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks
Adalimumab: 18 weekly doses of adalimumab | 4 |
| MTX 12.5 mg Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks
Adalimumab:18 weekly doses of adalimumab | 8 |
| MTX 25 mg Participants randomized to receive Methotrexate 25.0 mg at Week 00 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks
Adalimumab: 18 weekly doses of adalimumab | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | MTX 12.5 mg | MTX 25 mg | Total | Placebo |
|---|---|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 13.7 | 48.5 years STANDARD_DEVIATION 13.5 | 46.5 years STANDARD_DEVIATION 13.3 | 41.9 years STANDARD_DEVIATION 14.6 |
| C-Reactive protein (CRP) | 5.2 mg/L STANDARD_DEVIATION 2.7 | 15.1 mg/L STANDARD_DEVIATION 16.1 | 9.9 mg/L STANDARD_DEVIATION 11.8 | 6.6 mg/L STANDARD_DEVIATION 3.9 |
| Disease Duration (Years) | 5.1 years STANDARD_DEVIATION 3.7 | 7.0 years STANDARD_DEVIATION 9.3 | 7.0 years STANDARD_DEVIATION 7.4 | 10.8 years STANDARD_DEVIATION 8 |
| Fecal Calprotectin | 675.8 ug/g STANDARD_DEVIATION 431.6 | 545.2 ug/g STANDARD_DEVIATION 362 | 603.7 ug/g STANDARD_DEVIATION 400.1 | 606.7 ug/g STANDARD_DEVIATION 566.6 |
| Mayo Clinic Score | 8.6 units on a scale STANDARD_DEVIATION 2.1 | 8.7 units on a scale STANDARD_DEVIATION 2.1 | 8.7 units on a scale STANDARD_DEVIATION 1.9 | 9.0 units on a scale STANDARD_DEVIATION 1.2 |
| Sex/Gender, Customized Female | 5 Participants | 3 Participants | 8 Participants | 0 Participants |
| Sex/Gender, Customized Male | 3 Participants | 7 Participants | 14 Participants | 4 Participants |
| Weight | 75.5 kg STANDARD_DEVIATION 15.2 | 89.6 kg STANDARD_DEVIATION 20.5 | 81.8 kg STANDARD_DEVIATION 18.5 | 75.0 kg STANDARD_DEVIATION 15.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 8 / 8 | 5 / 10 |
| serious Total, serious adverse events | 0 / 4 | 2 / 8 | 1 / 10 |
Outcome results
Primary
Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups
The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance
Time frame: Baseline up to Week 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups | 0.7 score on a scale | Standard Deviation 1.2 |
| MTX 12.5mg | Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups | 1.1 score on a scale | Standard Deviation 1.6 |
| MTX 25 mg | Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups | 0.9 score on a scale | Standard Deviation 1.8 |
p-value: 0.758Wilcoxon (Mann-Whitney)
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.
UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration). The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity. The mean change and 95% CI are based on least square means from the analysis of covariance
Time frame: Baseline up to Week 18
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups. | 0.5 score on a scale |
| MTX 12.5mg | Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups. | 0.7 score on a scale |
| MTX 25 mg | Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups. | 1.1 score on a scale |
p-value: 0.908ANCOVA