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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1156-8608 | Registry Identifier | WHO |
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This was an open-label study to provide an opportunity for participants with Ulcerative Colitis (UC) who previously completed Study C13002 (NCT01177228), and for treatment-naïve participants with UC or Crohn's Disease (CD) to receive treatment with vedolizumab, and to determine the long term safety of vedolizumab in patients afflicted with these diseases.
This was a phase 2, multiple-dose, open-label study of vedolizumab administered intravenously (IV) every 8 weeks. The study population included treatment-naïve ulcerative colitis (UC) or Crohn's Disease (CD) participants, as well as 38 UC participants who had tolerated vedolizumab well during Study C13002 (NCT01177228).
In the original study protocol, all participants were randomized to receive vedolizumab at doses of either 6 mg/kg or 10 mg/kg. With the implementation of Amendment 1, the assigned doses of vedolizumab were decreased to 2.0 mg/kg and 6.0 mg/kg. To implement the dose changes, instead of randomizing all participants across both doses, those who rolled over from Study C13002 were reassigned to receive the 2.0 mg/kg dose and all participants who entered C13004 naïve to treatment were to receive the 6.0 mg/kg dose, starting on the next scheduled dosing day. Also, if participants assigned to the 2 mg/kg dose experienced flare, they were to receive the higher 6 mg/kg dose.
In the results analyses for this study, participants are grouped according to the lowest dose received, i.e., 2.0 mg/kg or 6.0 mg/kg vedolizumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vedolizumab 2 mg/kg | Experimental | Participants received vedolizumab, 2 mg/kg, intravenously (IV), on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks. |
|
| Vedolizumab 6 mg/kg | Experimental | Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| vedolizumab | Drug | Vedolizumab for intravenous (IV) infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. The investigator systematically collected information adequate to determine both the outcome and severity of the AE, and whether or not it was drug-related or met the criteria for classification as a serious adverse event (SAE). An SAE was defined as an AE that resulted in (or posed risk for) death, inpatient hospitalization (or prolonging hospitalization), or congenital, persistent or significant disability/incapacity. The intensity for each AE was defined according to the following criteria: Mild: Awareness of sign or symptom, but easily tolerated; Moderate: Discomfort enough to cause interference with normal daily activities; Severe: Inability to perform normal daily activities. | From Day 1 to Day 637 |
| Number of Participants With Clinically Significant Laboratory Findings | Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes in the blood. | through Day 637 |
| Number of Participants With Signs and Symptoms of Progressive Multifocal Leukoencephalopathy (PML) | At every visit, before receiving study treatment participants were evaluated by clinic staff for signs of PML using a PML symptom checklist. | through Day 637 |
| Number of Participants With Human Anti-human Antibodies (HAHA) | Samples collected prior to dosing on Days 1, 43, 155, 267, 379, 491, and 637. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Concentration of Vedolizumab Before Dosing | Vedolizumab serum concentrations were measured from serum samples collected for pharmacokinetic (PK) analysis within 2 hours prior to dosing. The original protocol specified that PK parameters, including but not limited to minimum plasma concentration (Cmin), were to be estimated; however, due to intrapatient dose modification with Amendment 1, it was no longer feasible to perform a full PK parameter estimation. The summaries of pre-infusion data (i.e., trough levels) are presented at time points where at least 50% of participants had quantifiable vedolizumab concentrations, using a value of 0 for results below a measurable range. This provides information on the pharmacokinetic behavior of vedolizumab when administered as long-term therapy. |
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Inclusion Criteria:
Confirmed and active ulcerative colitis (UC) or Crohn's Disease (CD)
Patient should be appropriate candidate for biologic therapy per guidelines
Up-to-date on cancer screening
No severe systemic disease
Patients with evidence of abscess
Agree to comply with study procedures including contraception
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| London Health Sciences Centre | London | Ontario | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26893500 | Derived | Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D'Haens G, Panaccione R, Loftus EV Jr, Sankoh S, Fox I, Parikh A, Milch C, Abhyankar B, Feagan BG. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017 May;66(5):839-851. doi: 10.1136/gutjnl-2015-311079. Epub 2016 Feb 18. |
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Treatment-naïve ulcerative colitis (UC) or Crohn's Disease (CD) participants were assigned to receive 6.0 mg/kg vedolizumab. Participants who rolled over from Study C13002 (NCT01177228) were assigned to receive 2.0 mg/kg vedolizumab.
Participants took part in the study at 14 investigative sites in Canada and Russia, between 07 December 2007 and 31 March 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vedolizumab 2 mg/kg | Participants received vedolizumab, 2 mg/kg, intravenously (IV), on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks |
| FG001 | Vedolizumab 6 mg/kg | Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Safety Analysis Set defined as all enrolled participants who received at least 1 dose of study drug. Patients were analyzed based on the lowest dose they received.
Baseline is the time closest to, but before, the start of study drug administration; for participants who rolled over from Study C13002 Baseline data are from the C13002 dataset.
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| ID | Title | Description |
|---|---|---|
| BG000 | Vedolizumab 2 mg/kg | Participants received vedolizumab, 2 mg/kg, intravenously (IV), on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks |
| BG001 | Vedolizumab 6 mg/kg |
| 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 | Number of Participants With Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. The investigator systematically collected information adequate to determine both the outcome and severity of the AE, and whether or not it was drug-related or met the criteria for classification as a serious adverse event (SAE). An SAE was defined as an AE that resulted in (or posed risk for) death, inpatient hospitalization (or prolonging hospitalization), or congenital, persistent or significant disability/incapacity. The intensity for each AE was defined according to the following criteria: Mild: Awareness of sign or symptom, but easily tolerated; Moderate: Discomfort enough to cause interference with normal daily activities; Severe: Inability to perform normal daily activities. | Safety analysis set, defined as all enrolled participants who received at least 1 dose of study drug. Analysis was based on the lowest dose received, rather than dose at randomization. | Posted | Number | participants | From Day 1 to Day 637 |
|
From Day 1 to Day 637
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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 | Vedolizumab 2 mg/kg | Participants received vedolizumab, 2 mg/kg, intravenously (IV), on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal abscess | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Millennium Pharmaceuticals Inc | 800-778-2860 | clinicaltrialregistry@tpna.com |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C543529 | vedolizumab |
| C438271 | LDP-02 |
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| Days 43, 99, 155 and 267, predose |
| Saturation of Receptors by Vedolizumab Before Dosing on Days 1, 43, 99, 155 and 267 by ACT-1 Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the ACT-1 binding interference assay. ACT-1 is a mouse antibody similar to vedolizumab that also binds α4β7 integrin. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Days 43, 99, 155 and 267, predose |
| Saturation of Receptors by Vedolizumab Before Dosing Using the MAdCAM-1-Fc Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the mucosal address in cell adhesion molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the MAdCAM-1-Fc binding interference assay at time points where at least 50% of participants in the analysis set had non-missing results. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Days 43, 99, 155 and 267, predose |
| Lack of Efficacy |
|
| Rolled over to Study C13008 (NCT00790933 |
|
Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Body Surface Area (BSA) | Mean | Standard Deviation | m^2 |
|
| Inflammatory Bowel Disease Type | Number | participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | Vedolizumab 2 mg/kg | Participants received vedolizumab, 2 mg/kg, intravenously (IV), on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks |
| OG001 | Vedolizumab 6 mg/kg | Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks |
|
|
| Primary | Number of Participants With Clinically Significant Laboratory Findings | Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes in the blood. | Safety analysis set | Posted | Number | participants | through Day 637 |
|
|
|
| Primary | Number of Participants With Signs and Symptoms of Progressive Multifocal Leukoencephalopathy (PML) | At every visit, before receiving study treatment participants were evaluated by clinic staff for signs of PML using a PML symptom checklist. | Safety analysis set | Posted | Number | participants | through Day 637 |
|
|
|
| Primary | Number of Participants With Human Anti-human Antibodies (HAHA) | Safety analysis set | Posted | Number | participants | Samples collected prior to dosing on Days 1, 43, 155, 267, 379, 491, and 637. |
|
|
|
| Secondary | Serum Concentration of Vedolizumab Before Dosing | Vedolizumab serum concentrations were measured from serum samples collected for pharmacokinetic (PK) analysis within 2 hours prior to dosing. The original protocol specified that PK parameters, including but not limited to minimum plasma concentration (Cmin), were to be estimated; however, due to intrapatient dose modification with Amendment 1, it was no longer feasible to perform a full PK parameter estimation. The summaries of pre-infusion data (i.e., trough levels) are presented at time points where at least 50% of participants had quantifiable vedolizumab concentrations, using a value of 0 for results below a measurable range. This provides information on the pharmacokinetic behavior of vedolizumab when administered as long-term therapy. | The PK Population included all participants who received at least 1 dose of vedolizumab and had sufficient blood sampling for estimation of PK parameters. Participants without dose modification and with available serum concentration data at each time point (indicated by "n") are included. | Posted | Mean | Standard Deviation | μg/mL | Days 43, 99, 155 and 267, predose |
|
|
|
| Secondary | Saturation of Receptors by Vedolizumab Before Dosing on Days 1, 43, 99, 155 and 267 by ACT-1 Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the ACT-1 binding interference assay. ACT-1 is a mouse antibody similar to vedolizumab that also binds α4β7 integrin. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Pharmacodynamic (PD) Population included all participants who received at least 1 dose of vedolizumab and had sufficient blood sampling for estimation of PD parameters. Participants without dose modification and with available PD data at each time point are included. | Posted | Mean | Standard Deviation | % ACT1 binding | Days 43, 99, 155 and 267, predose |
|
|
|
| Secondary | Saturation of Receptors by Vedolizumab Before Dosing Using the MAdCAM-1-Fc Assay | The target of vedolizumab is α4β7 integrin, a receptor found on inflammatory immune cells that guides these inflammatory cells to the gut and binds to the mucosal address in cell adhesion molecule-1 (MAdCAM-1) on gut endothelial cells. The extent of the α4β7 receptor saturation by vedolizumab was assessed using the MAdCAM-1-Fc binding interference assay at time points where at least 50% of participants in the analysis set had non-missing results. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody. The assay measures the percentage of cells bearing α4β7 that were not saturated with vedolizumab at the time of sampling. | Pharmacodynamic (PD) Population included all participants who received at least 1 dose of vedolizumab and had sufficient blood sampling for estimation of PD parameters. Participants without dose modification and with available PD data at each time point are included. | Posted | Mean | Standard Deviation | percent MADCAM binding | Days 43, 99, 155 and 267, predose |
|
|
|
| 3 |
| 37 |
| 12 |
| 37 |
| EG001 | Vedolizumab 6 mg/kg | Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks | 7 | 35 | 27 | 35 |
| Salmonella sepsis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Colitis ulcerative | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Crohn's disease | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment | Crohn's Disease (CD) relapse among CD patients |
|
| Vision blurred | Eye disorders | MedDRA (9.1) | Systematic Assessment |
|
| Infusion-related reaction | General disorders | MedDRA (9.1) | Systematic Assessment |
|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA (9.1) | Systematic Assessment |
|
| Uterine polyp | Reproductive system and breast disorders | MedDRA (9.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| Carpal tunnel syndrome | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| Crohn's disease | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment | Crohn's Disease (CD) relapse among CD patients |
|
| Nausea | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (9.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (9.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| White Blood Cells Decreased |
|
| C-reactive Protein Increased |
|
| Hypokalemia |
|
| Hypomagnesemia |
|
| Hepatic enzyme increased |
|
| ALT and AST Increased |
|
| Day 155 (n=26, 17) |
|
| Day 267 (n=26, 12) |
|
| Day 99 (n=26, 17) |
|
| Day 155 (n=26, 17) |
|
| Day 267 (n=25, 12) |
|
| Day 99 (n=26, 16) |
|
| Day 155 (n=26, 16) |
|
| Day 267 (n=25, 12) |
|