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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000517-40 | EudraCT Number | ||
| MK-2155-195 |
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This study will evaluate biomarkers that reflect changes in gut mucosal status during therapy with infliximab and determine whether changes in the levels of the selected biomarkers can be used to predict endoscopically assessed gut mucosal status changes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Infliximab 5 mg/kg | Infliximab treatment and endoscopy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infliximab | Drug | Infliximab administered intravenously at a dose of 5 mg/kg at study Weeks 0, 2, 6, 14, and 22. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6 | CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 6 minus baseline CDEIS scores, with a negative change from baseline indicating improvement. | Baseline and Week 6 |
| Change From Baseline in CDEIS Blinded Score at Week 22 | CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 22 minus baseline CDEIS scores, with a negative change from baseline indicating improvement. | Baseline and Week 22 |
| Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6 | Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers | Based on two measurements at baseline, the concordance correlation coefficient (CCC) was computed for each of four biomarkers, using a mixed effects model with a fixed factor for repeat measurements and a random factor for participant. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements. |
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Inclusion Criteria:
Exclusion Criteria:
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Approximately 20 participants aged 18 to 60 years with Crohn's Disease will be enrolled from gastrointestinal specialist clinics.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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Participants 18 to 60 years of age, with moderate to severe Crohn's Disease (CD) who had not been previously treated with anti-inflammatory biologic agents were enrolled in this trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | Infliximab 5mg/kg | Infliximab administered intravenously at a dose of 5 mg/kg at study weeks 0, 2, 6, 14, and 22 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Infliximab 5mg/kg | Infliximab administered intravenously at a dose of 5 mg/kg at study weeks 0, 2, 6, 14, and 22 |
| 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 From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6 | CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 6 minus baseline CDEIS scores, with a negative change from baseline indicating improvement. | Participants who had a blinded CDEIS score at both baseline and at Week 6. | Posted | Mean | Standard Deviation | Score on a scale | Baseline and Week 6 |
From 4 weeks prior to first dose, until 2 weeks after last dose (up to 28 weeks)
All enrolled participants
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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 | Pre-study | From 4 weeks prior to first dose, up to first dose of infliximab |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Crohn's disease | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000069285 | Infliximab |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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stool, serum, peripheral blood mononuclear cells (PBMC)
| Baseline and Week 6 |
| Change From Baseline in Serum hsCRP at Week 22 | Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Baseline and Week 22 |
| Change From Baseline in Stool Calprotectin at Week 6 | Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. | Baseline and Week 6 |
| Change From Baseline in Stool Calprotectin at Week 22 | Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Baseline and Week 22 |
| Change From Baseline in Serum Lipocalin-2 at Week 6 | Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. | Baseline and Week 6 |
| Change From Baseline in Serum Lipocalin-2 at Week 22 | Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Baseline and Week 22 |
| Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6 | Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. | Baseline and Week 6 |
| Change From Baseline in REG3-A at Week 22 | Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Baseline and Week 22 |
| Coefficient of Determination (R^2) For Predicting The Change From Baseline In Blinded CDEIS Score From The Changes From Baseline In Four Biomarkers At Weeks 6 and 22 | To determine R^2 a multiple linear regression analysis was conducted with the change from baseline in CDEIS score as the response variable and the baseline CDEIS score, changes from baseline in the four biomarkers serum hsCRP, serum lipocalin-2, serum Reg3-A, and stool calprotectin (their concentrations were log-transformed to make the mean function of the response more linear) at Weeks 6 and 22 as the predictor variables. CDEIS scores were provided by a blinded observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy. The R^2 can range from 0 to 1; with higher values indicating greater predictability of the model. The primary hypothesis is that the true R^2 at weeks 6 and 22 is approximately 0.7. | Baseline and Week 6 or 22 |
| Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing) |
| Concordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation | The CCC of blinded (central) versus unblinded (site) scores from either CDEIS or the Simple Endoscopic Score for Crohn's Disease (SES-CD) was determined at Baseline, Week 6 and Week 22. SES-CD sums the following scores: presence and size of ulcers in five visualized bowel segments; extent of ulcerated surface in five visualized bowel segments; extent of affected surface in five visualized bowel segments; presence and type of narrowings in five visualized bowel segments; and can range from 0-56, with a higher sum indicating greater severity of mucosal inflammation. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements. | Baseline, Week 6, Week 22 |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Infliximab 5 mg/kg | Infliximab administered intravenously at a dose of 5 mg/kg at study weeks 0, 2, 6, 14, and 22 |
|
|
| Primary | Change From Baseline in CDEIS Blinded Score at Week 22 | CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 22 minus baseline CDEIS scores, with a negative change from baseline indicating improvement. | Participants who had a blinded CDEIS score at both baseline and at Week 22. | Posted | Mean | Standard Deviation | Score on a scale | Baseline and Week 22 |
|
|
|
| Primary | Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6 | Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. | Participants with measurements for hsCRP at both baseline and at Week 6. | Posted | Mean | Standard Deviation | mg/L | Baseline and Week 6 |
|
|
|
| Primary | Change From Baseline in Serum hsCRP at Week 22 | Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Participants with measurements for hsCRP at both baseline and at Week 22. | Posted | Mean | Standard Deviation | mg/L | Baseline and Week 22 |
|
|
|
| Primary | Change From Baseline in Stool Calprotectin at Week 6 | Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. | Participants with measurements for calprotectin at both baseline and at Week 6. | Posted | Mean | Standard Deviation | µg/g | Baseline and Week 6 |
|
|
|
| Primary | Change From Baseline in Stool Calprotectin at Week 22 | Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Participants with measurements for calprotectin at both baseline and at Week 22. | Posted | Mean | Standard Deviation | µg/g | Baseline and Week 22 |
|
|
|
| Primary | Change From Baseline in Serum Lipocalin-2 at Week 6 | Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. | Participants with measurements for lipocalin-2 at both baseline and at Week 6. | Posted | Mean | Standard Deviation | ng/mL | Baseline and Week 6 |
|
|
|
| Primary | Change From Baseline in Serum Lipocalin-2 at Week 22 | Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Participants with measurements for lipocalin-2 at both baseline and at Week 22. | Posted | Mean | Standard Deviation | ng/mL | Baseline and Week 22 |
|
|
|
| Primary | Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6 | Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline. | Participants with measurements for REG3-A at both baseline and at Week 6. | Posted | Mean | Standard Deviation | ng/mL | Baseline and Week 6 |
|
|
|
| Primary | Change From Baseline in REG3-A at Week 22 | Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline. | Participants with measurements for REG3-A at both baseline and at Week 22. | Posted | Mean | Standard Deviation | ng/mL | Baseline and Week 22 |
|
|
|
| Primary | Coefficient of Determination (R^2) For Predicting The Change From Baseline In Blinded CDEIS Score From The Changes From Baseline In Four Biomarkers At Weeks 6 and 22 | To determine R^2 a multiple linear regression analysis was conducted with the change from baseline in CDEIS score as the response variable and the baseline CDEIS score, changes from baseline in the four biomarkers serum hsCRP, serum lipocalin-2, serum Reg3-A, and stool calprotectin (their concentrations were log-transformed to make the mean function of the response more linear) at Weeks 6 and 22 as the predictor variables. CDEIS scores were provided by a blinded observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy. The R^2 can range from 0 to 1; with higher values indicating greater predictability of the model. The primary hypothesis is that the true R^2 at weeks 6 and 22 is approximately 0.7. | Participants who had a blinded CDEIS score and measurements for each of the biomarkers included in the models at both baseline and at Week 6 or 22. | Posted | Number | Coefficient of Determination | Baseline and Week 6 or 22 |
|
|
|
|
| Secondary | Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers | Based on two measurements at baseline, the concordance correlation coefficient (CCC) was computed for each of four biomarkers, using a mixed effects model with a fixed factor for repeat measurements and a random factor for participant. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements. | Participants who had both baseline serum or stool measurements available for analysis. | Posted | Number | 90% Confidence Interval | Correlation coefficient | Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing) |
|
|
|
| Secondary | Concordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation | The CCC of blinded (central) versus unblinded (site) scores from either CDEIS or the Simple Endoscopic Score for Crohn's Disease (SES-CD) was determined at Baseline, Week 6 and Week 22. SES-CD sums the following scores: presence and size of ulcers in five visualized bowel segments; extent of ulcerated surface in five visualized bowel segments; extent of affected surface in five visualized bowel segments; presence and type of narrowings in five visualized bowel segments; and can range from 0-56, with a higher sum indicating greater severity of mucosal inflammation. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements. | Participants who had both blinded and unblinded scores available for analysis. | Posted | Number | 90% Confidence Interval | Correlation coefficient | Baseline, Week 6, Week 22 |
|
|
|
| 0 |
| 15 |
| 7 |
| 15 |
| EG001 | Infliximab 5mg/kg | Infliximab administered intravenously at a dose of 5 mg/kg at study weeks 0, 2, 6, 14, and 22 | 2 | 15 | 13 | 15 |
| EG002 | Post-study | From last dose of study drug, up to 24 days after last dose of infliximab | 0 | 15 | 0 | 15 |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA 18.1 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Aphthous ulcer | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Gastrointestinal sounds abnormal | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Axillary pain | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
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| Procedural hypotension | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
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| Iron deficiency | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
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| Bladder pain | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, and on the presentation with regard to the following: proprietary information; the accuracy of the information; and that the presentation is fairly balanced and in compliance with FDA regulations.
| D007410 | Intestinal Diseases |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Superiority or Other |
|
| stool calprotectin (n=15) |
|
|
| SES-CD Baseline (n = 15) |
|
| SES-CD Week 6 (n = 13) |
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| SES-CD Week 22 (n = 13) |
|