A Phase 2 interventional study of Vedolizumab and Placebo in Ulcerative Colitis, sponsored by Millennium Pharmaceuticals, Inc.. Completed. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2014-07-18.
Sponsored by Millennium Pharmaceuticals, Inc. (part of Takeda) · Phase 2, Interventional, and Treatment
The main objectives of this study were to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of vedolizumab in patients with ulcerative colitis (UC).
At the end of the study, eligible participants could enroll and receive treatment and follow-up in Study C13004 (NCT00619489). Participants who did not proceed into Study C13004 were followed by telephone contact at 6-month intervals for 2 years after the last administration of study treatment to collect reports of adverse events, including colectomy, severe infections [including progressive multifocal leukoencephalopathy (PML)], and dysplasia/cancer.
1,530 studies on the registry are indexed under Colitis, Ulcerative; 407 are open to participants now.
This study's enrollment of 47 is below the median of 70 across 1,069 interventional studies indexed under Colitis, Ulcerative.
Browse Colitis, Ulcerative studies →Millennium Pharmaceuticals, Inc. is the lead sponsor of 178 studies on the registry; none are open to participants now.
Of its 74 completed or terminated interventional studies of FDA-regulated products, 73 (99%) have results posted.
First submitted after Millennium Pharmaceuticals, Inc. became part of Takeda.
Counted across the registry records on this site, refreshed daily.
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Each patient must meet all of the following inclusion criteria to be enrolled in the study.
Confirmed and active ulcerative colitis (UC)
Exclusion Criteria:
Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
Vedolizumab-matching placebo, intravenous (IV), infusion on Days 1, 15, 29 and 85.
Drug: Placebo
Vedolizumab, 2 mg/kg, IV infusion on Days 1, 15, 29 and 85.
Drug: Vedolizumab
Vedolizumab 6 mg/kg, IV infusion on Days 1, 15, 29 and 85.
Drug: Vedolizumab
Vedolizumab 10 mg/kg, IV infusion on Days 1, 15, 29 and 85.
Drug: Vedolizumab
Vedolizumab for intravenous infusion
Also known as: Entyvio, MLN0002, MLN02, LDP-02
Placebo intravenous infusion
Number of Participants With Adverse Events
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.
Time frame: From the first date of study drug administration through Day 253
Cmax: Maximum Observed Plasma Concentration of Vedolizumab on Days 1 and 85
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Days 1 and 85, prior to and 2, 12, 24, 48, and 72 hours after dosing.
Cmin: Minimum Observed Plasma Concentration of Vedolizumab
Minimum observed plasma concentration (Cmin) is the lowest plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Day 85, prior to and 2, 12, 24, 48, and 72 hours after dosing.
Area Under the Plasma Concentration-Time Curve (AUC) for Vedolizumab
AUC was calculated for 3 time intervals during the study: 1. AUC (Day 0-14): from administration on Day 0 to last quantifiable concentration on Day 14, selected to capture the AUC following the first dose of vedolizumab until administration of the second dose 2. AUC(Day 85-99): from administration on Day 85 to last quantifiable concentration on Day 99, selected to assess the amount of drug accumulation with the planned loading regimen by comparing it to AUC(Day 0-14) 3. AUC(Day 85-141): from the first quantifiable concentration on Day 85 to the last quantifiable concentration on Day 141, selected to assess the drug exposure over an 8-week period
Time frame: Days 0-14, Days 85-99, Days 85-141
Terminal Phase Elimination Half-life (t½) of Vedolizumab
Terminal phase elimination half-life (t½) is the time required for half of the drug to be eliminated from the plasma.
Time frame: Pre-dose through Day 253
Maximum Drug Effect (Emax) of Vedolizumab as Measured by Percent Inhibition of the Act-1 Marker
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 percent inhibition of the Act-1 due to the presence of vedolizumab binding. Emax was calculated on Day 1, Day 85 and based on all available data.
Time frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71, 85, 86, 87, 89, 92, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, and 253
Maximum Drug Effect (Emax) as Measured by Inhibition of the MAdCAM-1-Fc Marker
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 MAdCAM-1-Fc binding interference assay. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody. The assay measures the percent inhibition of the MAdCAM-1-Fc binding to α4β7 integrin due to the presence of vedolizumab binding. Emax was calculated on Day 1, Day 85, and based on all available data.
Time frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71, 85, 86, 87, 89, 92, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, and 253
Area Under the Drug Effect Time Curve [AUEC(0-last)] as Measured by Inhibition of the ACT-1 Marker
AUEC (0-last) is the area under the drug effect-time curve until the last available time point. Mean percent inhibition over time \[AUEC(0-last)\] was determined for the Act-1 marker. Act-1 is a mouse antibody similar to vedolizumab that also binds α4β7 integrin.
Time frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71, 85, 86, 87, 89, 92, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, and 253
Area Under the Drug Effect Time Curve [AUEC(0-last)] as Measured by Inhibition of the MAdCAM-1-Fc Marker
AUEC (0-last) is the area under the drug effect-time curve until the last available time point. Mean percent inhibition over time \[AUEC(0-last)\] was determined for the MAdCAM-1-Fc marker. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody.
Time frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71, 85, 86, 87, 89, 92, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, and 253
Participants took part in the study at 2 study centers in Canada and 9 study centers in Russia, from 02 May 2007 to 16 June 2008.
| Milestone | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Started | 9 | 13 | 14 | 11 |
| Received treatment | 9 | 12 | 14 | 11 |
| Completed | 8 | 11 | 14 | 11 |
| Not completed | 1 | 2 | 0 | 0 |
| Withdrew: Positive tuberculosis test | 0 | 1 | 0 | 0 |
| Withdrew: Worsening disease activity | 1 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 |
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.
| participants | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Any Adverse Event | 7 | 9 | 9 | 6 |
| Severe Adverse Event | 0 | 0 | 1 | 1 |
| Drug-related Adverse Event | 3 | 2 | 1 | 1 |
| Serious Adverse Event | 0 | 1 | 0 | 1 |
| Drug-related Serious Adverse Event | 0 | 0 | 0 | 0 |
| Serious Adverse Event Resulting in Discontinuation | 0 | 0 | 0 | 0 |
| On-study Deaths | 0 | 0 | 0 | 0 |
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
| µg/mL | Vedolizumab 2 mg/kg | Vedolizumab (6 mg/kg) | Vedolizumab 10 mg/kg |
|---|---|---|---|
| Cmax, Day 1 (n=10, 14, 11) | 54.0 ± 8.9 | 154.3 ± 41.5 | 279.0 ± 167.9 |
| Cmax, Day 85 (n=9, 14, 11) | 60.4 ± 12.5 | 191.9 ± 42.6 | 291.9 ± 95.0 |
Minimum observed plasma concentration (Cmin) is the lowest plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
| μg/mL | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|
| Cmin: Minimum Observed Plasma Concentration of Vedolizumab | 7.25 ± 2.41 | 29.33 ± 13.36 | 44.74 ± 19.80 |
AUC was calculated for 3 time intervals during the study: 1. AUC (Day 0-14): from administration on Day 0 to last quantifiable concentration on Day 14, selected to capture the AUC following the first dose of vedolizumab until administration of the second dose 2. AUC(Day 85-99): from administration on Day 85 to last quantifiable concentration on Day 99, selected to assess the amount of drug accumulation with the planned loading regimen by comparing it to AUC(Day 0-14) 3. AUC(Day 85-141): from the first quantifiable concentration on Day 85 to the last quantifiable concentration on Day 141, selected to assess the drug exposure over an 8-week period
| day*μg/mL | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|
| AUC (Day 0-14) (n=10, 14, 11) | 375 ± 59 | 1058 ± 270 | 1765 ± 822 |
| AUC(Day 85-99) (n=9, 14, 11) | 473 ± 92 | 1532 ± 227 | 2608 ± 795 |
| AUC(Day 85-141) (n=9, 14, 11) | 1082 ± 243 | 3318 ± 698 | 5633 ± 1927 |
Terminal phase elimination half-life (t½) is the time required for half of the drug to be eliminated from the plasma.
| days | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|
| Terminal Phase Elimination Half-life (t½) of Vedolizumab | 15.1 ± 2.0 | 22.0 ± 6.7 | 20.6 ± 7.2 |
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 percent inhibition of the Act-1 due to the presence of vedolizumab binding. Emax was calculated on Day 1, Day 85 and based on all available data.
| percent inhibition | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Day 1 (n=8, 10, 12, 11) | 18.4 ± 19.3 | 98.0 ± 1.1 | 99.0 ± 0.8 | 98.3 ± 1.3 |
| Day 85 (n=8, 9, 12, 11) | 22.8 ± 15.3 | 98.7 ± 1.2 | 99.1 ± 0.7 | 98.6 ± 0.8 |
| All available (n=8, 10, 12, 11) | 56.3 ± 29.4 | 99.5 ± 0.6 | 99.8 ± 0.3 | 99.8 ± 0.3 |
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 MAdCAM-1-Fc binding interference assay. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody. The assay measures the percent inhibition of the MAdCAM-1-Fc binding to α4β7 integrin due to the presence of vedolizumab binding. Emax was calculated on Day 1, Day 85, and based on all available data.
| percent inhibition | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Day 1 (n=8, 10, 11, 10) | 11.9 ± 15.3 | 96.4 ± 1.8 | 89.8 ± 29.8 | 96.8 ± 2.9 |
| Day 85 (n=8, 9, 11, 10) | 8.5 ± 7.9 | 98.3 ± 1.1 | 98.3 ± 2.3 | 96.2 ± 2.6 |
| All available (n=8, 10, 11, 10) | 43.3 ± 27.3 | 99.3 ± 0.6 | 99.8 ± 0.3 | 99.3 ± 0.7 |
AUEC (0-last) is the area under the drug effect-time curve until the last available time point. Mean percent inhibition over time \[AUEC(0-last)\] was determined for the Act-1 marker. Act-1 is a mouse antibody similar to vedolizumab that also binds α4β7 integrin.
| percent inhibition*days | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Area Under the Drug Effect Time Curve [AUEC(0-last)] as Measured by Inhibition of the ACT-1 Marker | 4281.7 ± 3035.3 | 20195.9 ± 3814.2 | 22675.2 ± 2211.8 | 23613.7 ± 1574.4 |
AUEC (0-last) is the area under the drug effect-time curve until the last available time point. Mean percent inhibition over time \[AUEC(0-last)\] was determined for the MAdCAM-1-Fc marker. MAdCAM-1-Fc is a fusion of human MAdCAM-1 with parts of a mouse monoclonal antibody.
| percent inhibition*days | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Area Under the Drug Effect Time Curve [AUEC(0-last)] as Measured by Inhibition of the MAdCAM-1-Fc Marker | 2139.2 ± 1513.4 | 18802.0 ± 3556.1 | 22322.1 ± 1974.2 | 22484.6 ± 1716.0 |
Collected over Adverse events were collected through Day 253 or the final study visit.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 0/9 (0%) | 7/9 (77.8%) |
| Vedolizumab 2 mg/kg | — | 1/12 (8.3%) | 9/12 (75%) |
| Vedolizumab 6 mg/kg | — | 0/14 (0%) | 9/14 (64.3%) |
| Vedolizumab 10 mg/kg | — | 1/11 (9.1%) | 6/11 (54.5%) |
| Event | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Spinal compression fractureInjury, poisoning and procedural complications | 0/9 | 0/12 | 0/14 | 1/11 |
| GastroduodenitisGastrointestinal disorders | 0/9 | 1/12 | 0/14 | 0/11 |
| Event | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg |
|---|---|---|---|---|
| Colitis ulcerativeGastrointestinal disorders | 4/9 | 2/12 | 1/14 | 0/11 |
| Upper respiratory tract infectionInfections and infestations | 3/9 | 1/12 | 1/14 | 1/11 |
| HeadacheNervous system disorders | 1/9 | 2/12 | 3/14 | 2/11 |
| NasopharyngitisInfections and infestations | 1/9 | 2/12 | 1/14 | 0/11 |
| CoughRespiratory, thoracic and mediastinal disorders | 0/9 | 0/12 | 2/14 | 0/11 |
| Influenza like illnessGeneral disorders | 0/9 | 0/12 | 2/14 | 0/11 |
| PyrexiaGeneral disorders | 0/9 | 0/12 | 2/14 | 0/11 |
| Herpes zosterInfections and infestations | 1/9 | 0/12 | 0/14 | 0/11 |
| Lobar pneumoniaInfections and infestations | 1/9 | 0/12 | 0/14 | 0/11 |
| MastitisInfections and infestations | 1/9 | 0/12 | 0/14 | 0/11 |
Baseline measures are reported for the Safety Analysis Set - all enrolled participants who received at least 1 dose of study treatment. One participant was randomized but not dosed and is not included in this population.
| Age, Continuous(years) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Mean | 34.2 ± 8.11 | 39.0 ± 6.06 | 44.4 ± 12.37 | 44.3 ± 14.99 | 41.0 ± 11.46 |
| Sex: Female, Male(Participants) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Female | 6 | 8 | 7 | 6 | 27 |
| Male | 3 | 4 | 7 | 5 | 19 |
| Race/Ethnicity, Customized(participants) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| White, Not Hispanic or Latino | 9 | 12 | 14 | 11 | 46 |
| Height(cm) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Mean | 168.0 ± 7.33 | 169.8 ± 10.52 | 167.9 ± 9.87 | 170.7 ± 8.15 | 169.1 ± 9.00 |
| Weight(kg) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Mean | 74.01 ± 24.04 | 75.76 ± 20.98 | 79.61 ± 16.65 | 73.46 ± 13.60 | 76.04 ± 18.38 |
| Body Mass Index (BMI)(kg/m²) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Mean | 26.22 ± 8.46 | 26.03 ± 5.58 | 28.51 ± 6.66 | 25.29 ± 5.07 | 26.64 ± 6.37 |
| Body Surface Area (BSA)(m²) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Mean | 1.84 ± 0.31 | 1.88 ± 0.30 | 1.92 ± 0.21 | 1.86 ± 0.20 | 1.88 ± 0.25 |
| Time Since Onset of Symptoms(years) | Placebo | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Vedolizumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Mean | 3.92 ± 2.79 | 6.25 ± 5.00 | 6.85 ± 4.31 | 7.03 ± 10.13 | 6.16 ± 6.08 |
5 further baseline measures are reported on the registry.
No study locations are listed for this record.
The record gives a start of May 2007, a primary completion of Jun 2008 and a completion of Sep 2008. It does not say whether these dates are actual or estimated.
Results were first posted in Jul 2014, 6 years 1 month after primary completion. A results delay was requested in Jun 2012.
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This study is completed, as verified in Jun 2014. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Vedolizumab
Millennium Pharmaceuticals, Inc. →