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Unable to achieve recruitment target.
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| Name | Class |
|---|---|
| Abbott | INDUSTRY |
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Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active ulcerative colitis.
Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate interaction in subjects with moderately to severely active UC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MTX 12.5 | Active Comparator | Receive once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX and/or placebo in addition to doses of adalimumab |
|
| MTX 25 mg | Active Comparator | Once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX in addition to doses of adalimumab |
|
| Placebo | Placebo Comparator | Once weekly oral dosing with placebo (n=20) two weeks prior to the initiation of adalimumab. Subjects will receive 18 weekly doses of placebo in addition to doses of adalimumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MTX 12.5 | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline up to Week 18 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brian Feagan, MD | Robarts Research Institute - Western University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16339095 | Background | Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. | |
| 22326435 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | MTX 25 mg | Participants randomized to receive Methotrexate 25.0 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | MTX 12.5 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Mean | Standard Deviation | score on a scale | Baseline up to Week 18 |
|
Through study completion, an average of 18 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis ulcerative | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr.Jenny Jeyarajah (Sr. Biostatistician) | Alimentiv (Formerly Robarts Clinical Trails) | jenny.jeyarajah@alimentiv.com |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000068879 | Adalimumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
|
| MTX 25 | Drug | 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 |
|
|
| Adalimumab | Drug | Subjects will receive 18 weekly doses of adalimumab |
|
|
| Baseline up to Week 18 |
| Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF, Reinisch W; EXTEND Investigators; Kumar A, Lazar A, Camez A, Lomax KG, Pollack PF, D'Haens G. Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial. Gastroenterology. 2012 May;142(5):1102-1111.e2. doi: 10.1053/j.gastro.2012.01.035. Epub 2012 Feb 8. |
| 21209123 | Background | Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, Panaccione R, Fedorak RN, Tighe MB, Huang B, Kampman W, Lazar A, Thakkar R. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011 Jun;60(6):780-7. doi: 10.1136/gut.2010.221127. Epub 2011 Jan 5. |
| 12584368 | Background | Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A, Rutgeerts P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601-8. doi: 10.1056/NEJMoa020888. |
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
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Disease Duration (Years) | Mean | Standard Deviation | years |
|
| Weight | Mean | Standard Deviation | kg |
|
| C-Reactive protein (CRP) | Mean | Standard Deviation | mg/L |
|
| Fecal Calprotectin | Mean | Standard Deviation | ug/g |
|
| Mayo Clinic Score | The Mayo Clinic Score includes 4 variables: stool frequency, rectal bleeding, a physician's global assessment, and endoscopic findings with flexible sigmoidoscopy. Each variable is scored on a 4-point scale (0-3 points) and summed to give a total disease activity score (maximum score = 12), with higher scores representing more severe disease activity | Mean | Standard Deviation | units on a scale |
|
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
| OG002 | MTX 25 mg | Participants randomized to receive Methotrexate 25.0 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 |
|
|
|
| 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 | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline up to Week 18 |
|
|
|
|
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | 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 | 2 | 8 | 8 | 8 |
| EG002 | 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 | 1 | 10 | 5 | 10 |
| Urosepsis | Infections and infestations | Systematic Assessment |
|
| Colitis ulcerative | Gastrointestinal disorders | Systematic Assessment |
|
| Dysgeusia | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Contusion | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Pallor | Vascular disorders | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Epigastric discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Throat irritation | Gastrointestinal disorders | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Erythema nodosum | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Eye pain | Eye disorders | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | Systematic Assessment |
|
| Asthenia | General disorders | Systematic Assessment |
|
| Injection site erythema | General disorders | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
|
The PI of this Investigator-Initiated study had right to prior publication. If PI did not commence publication within 12months after the close of trial at all sites or after PI's manuscript was accepted for publication, whichever occurs first, the Sub-I and Sub-Institution were free to publish or present, provided that the Sub-I provided to the PI any doc. to be submitted for publication at least 30days prior to the planned date of submission for publication to permit a review of the Manuscript.
| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |