A Phase 2 interventional study of vedolizumab in Ulcerative Colitis and Crohn's Disease, sponsored by Millennium Pharmaceuticals, Inc.. Completed at 1 site in Canada. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2014-07-18.
Sponsored by Millennium Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment
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.
1,073 studies on the registry are indexed under Colitis; 131 are open to participants now.
This study's enrollment of 72 is above the median of 60 across 771 interventional studies indexed under Colitis.
Browse Colitis studies →Millennium Pharmaceuticals, Inc. is the lead sponsor of 173 studies on the registry; none are open to participants now.
Of its 73 completed or terminated interventional studies of FDA-regulated products, 72 (99%) have results posted.
Counted across the registry records on this site, refreshed daily.
Confirmed and active ulcerative colitis (UC) or Crohn's Disease (CD)
Exclusion Criteria:
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.
Drug: vedolizumab
Participants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks.
Drug: vedolizumab
Vedolizumab for intravenous (IV) infusion
Also known as: Entyvio, MLN0002, MLN02, LDP-02
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.
Time frame: 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.
Time frame: 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.
Time frame: through Day 637
Number of Participants With Human Anti-human Antibodies (HAHA)
Time frame: Samples collected prior to dosing on Days 1, 43, 155, 267, 379, 491, and 637.
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.
Time frame: 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.
Time frame: 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.
Time frame: Days 43, 99, 155 and 267, predose
Participants took part in the study at 14 investigative sites in Canada and Russia, between 07 December 2007 and 31 March 2010.
| Milestone | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Started | 37 | 35 |
| Completed | 14 | 1 |
| Not completed | 23 | 34 |
| Withdrew: Adverse event | 0 | 7 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Withdrew: Lack of efficacy | 0 | 11 |
| Withdrew: Rolled over to study c13008 (nct00790933 | 22 | 15 |
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 | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Any Adverse Event | 21 | 35 |
| Severe Adverse Event | 2 | 9 |
| Drug-related Adverse Event | 5 | 21 |
| Adverse Event Resulting in Discontinuation | 0 | 7 |
| Serious Adverse Event | 3 | 7 |
| Drug-related Serious Adverse Event | 1 | 4 |
| Serious Adverse Event Resulting in Discontinuation | 0 | 5 |
| On-study Deaths | 0 | 0 |
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes in the blood.
| participants | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Anemia | 3 | 0 |
| White Blood Cells Increased | 0 | 1 |
| White Blood Cells Decreased | 0 | 1 |
| C-reactive Protein Increased | 1 | 0 |
| Hypokalemia | 0 | 2 |
| Hypomagnesemia | 0 | 1 |
| Hepatic enzyme increased | 0 | 1 |
| ALT and AST Increased | 0 | 1 |
At every visit, before receiving study treatment participants were evaluated by clinic staff for signs of PML using a PML symptom checklist.
| participants | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Number of Participants With Signs and Symptoms of Progressive Multifocal Leukoencephalopathy (PML) | 0 | 0 |
| participants | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Number of Participants With Human Anti-human Antibodies (HAHA) | 2 | 1 |
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.
| μg/mL | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Day 43 (n=27, 19) | 25.2 ± 6.68 | 76.2 ± 36.9 |
| Day 99 (n=24, 18) | 11.2 ± 4.33 | 32.5 ± 20.5 |
| Day 155 (n=26, 17) | 8.40 ± 3.65 | 26.4 ± 17.7 |
| Day 267 (n=26, 12) | 7.40 ± 3.18 | 25.2 ± 11.7 |
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.
| % ACT1 binding | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Day 1 (0, 20) | NA ± NA | 14.6 ± 4.46 |
| Day 43 (26, 19) | 0.277 ± 0.216 | 0.311 ± 0.200 |
| Day 99 (n=26, 17) | 0.596 ± 0.690 | 0.288 ± 0.271 |
| Day 155 (n=26, 17) | 0.700 ± 1.50 | 1.09 ± 3.31 |
| Day 267 (n=25, 12) | 0.276 ± 0.247 | 0.767 ± 1.48 |
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.
| percent MADCAM binding | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Day 1 (n=0, 20) | NA ± NA | 18.5 ± 5.95 |
| Day 43 (n=26, 19) | 0.538 ± 0.512 | 0.705 ± 1.29 |
| Day 99 (n=26, 16) | 1.22 ± 1.20 | 0.838 ± 0.950 |
| Day 155 (n=26, 16) | 0.646 ± 0.673 | 0.369 ± 0.540 |
| Day 267 (n=25, 12) | 1.05 ± 1.38 | 0.975 ± 1.55 |
Collected over From Day 1 to Day 637. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Vedolizumab 2 mg/kg | — | 3/37 (8.1%) | 12/37 (32.4%) |
| Vedolizumab 6 mg/kg | — | 7/35 (20%) | 27/35 (77.1%) |
| Event | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| Abdominal abscessInfections and infestations | 0/37 | 1/35 |
| Salmonella sepsisInfections and infestations | 0/37 | 1/35 |
| Viral infectionInfections and infestations | 0/37 | 1/35 |
| Small intestinal obstructionGastrointestinal disorders | 0/37 | 1/35 |
| Crohn's diseaseGastrointestinal disorders | 0/37 | 1/35 |
| Vision blurredEye disorders | 0/37 | 1/35 |
| Infusion-related reactionGeneral disorders | 0/37 | 1/35 |
| Abortion spontaneousPregnancy, puerperium and perinatal conditions | 0/37 | 1/35 |
| FuruncleInfections and infestations | 1/37 | 0/35 |
| Colitis ulcerativeGastrointestinal disorders | 1/37 | 0/35 |
| Event | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg |
|---|---|---|
| NasopharyngitisInfections and infestations | 5/37 | 7/35 |
| HeadacheNervous system disorders | 2/37 | 7/35 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/37 | 5/35 |
| InfluenzaInfections and infestations | 1/37 | 3/35 |
| Crohn's diseaseGastrointestinal disorders | 0/37 | 3/35 |
| NauseaGastrointestinal disorders | 0/37 | 3/35 |
| VomitingGastrointestinal disorders | 0/37 | 3/35 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/37 | 3/35 |
| Upper respiratory tract infectionInfections and infestations | 1/37 | 2/35 |
| Urinary tract infectionInfections and infestations | 0/37 | 2/35 |
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.
| Age, Continuous(years) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| Mean | 42.0 ± 11.06 | 42.1 ± 15.79 | 42.1 ± 13.47 |
| Sex: Female, Male(Participants) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| Female | 21 | 22 | 43 |
| Male | 16 | 13 | 29 |
| Ethnicity (NIH/OMB)(Participants) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 37 | 34 | 71 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Race/Ethnicity, Customized(participants) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| White | 37 | 34 | 71 |
| American Indian or Alaskan Native | 0 | 1 | 1 |
| Height(cm) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| Mean | 168.9 ± 8.83 | 168.4 ± 11.49 | 168.7 ± 10.14 |
| Weight(kg) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| Mean | 77.03 ± 17.620 | 70.81 ± 17.820 | 74.01 ± 17.868 |
| Body Mass Index (BMI)(kg/m^2) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| Mean | 27.04 ± 6.045 | 24.86 ± 5.286 | 25.98 ± 5.754 |
| Body Surface Area (BSA)(m^2) | Vedolizumab 2 mg/kg | Vedolizumab 6 mg/kg | Total |
|---|---|---|---|
| Mean | 1.89 ± 0.233 | 1.81 ± 0.270 | 1.85 ± 0.253 |
1 further baseline measures are reported on the registry.
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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Millennium Pharmaceuticals, Inc.