Ulcerative ColitisPhase 2NCT00619489
Long Term Safety of Vedolizumab (MLN0002) in Patients With Ulcerative Colitis and Crohn's Disease
A Phase 2 study testing vedolizumab in people with Ulcerative Colitis and Crohn's Disease, run by Millennium Pharmaceuticals, Inc. at 1 site in Canada.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis, Crohn's Disease
- What is being tested?
- vedolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2007to Mar 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed and active ulcerative colitis (UC) or Crohn's Disease (CD)
- Crohn's Disease Activity Index (CDAI) Score of 220 - 450 for participants with CD
- Partial Mayo score of 2 - 7 for participants with UC
- 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
Who cannot join
- Low lymphocyte counts
- History of imaging abnormalities, multiple sclerosis (MS), brain tumor or other neurological illness
- Active or recent serious infections
- Recent treatment with biologic (i.e., Remicade) or investigational drug
- Impending surgery
- Any participants with vedolizumab human anti-human antibody (HAHA) titers ≥1:125 or with a previous immediate hypersensitivity reaction during or shortly after vedolizumab infusion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2, Multiple Dose, Open-Label Study to Determine the Long Term Safety of MLN0002 in Patients With Ulcerative Colitis and Crohn's Disease
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.
Read the detailed description
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.
- Conditions
- Ulcerative Colitis, Crohn's Disease
- Being tested
- vedolizumab
- Medical subject headings
- Colitis, Ulcerative, Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vedolizumabDrug
Also called Entyvio, MLN0002, MLN02, LDP-02
Vedolizumab for intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: vedolizumab |
| 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. Receives: Drug: vedolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: through Day 637
Number of Participants With Human Anti-human Antibodies (HAHA)
Measured: Samples collected prior to dosing on Days 1, 43, 155, 267, 379, 491, and 637.
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Days 43, 99, 155 and 267, predose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2008 (estimated)
- Study startDec 2007
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00619489
- Sponsor's protocol ID
- C13004
- Other IDs
- U1111-1156-8608
- Status last verified
- Jun 2014
- First submitted
- 11 Feb 2008
- Last updated
- 18 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 26893500
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Multiple Dose, Open-Label Study to Determine the Long Term Safety of MLN0002 in Patients With Ulcerative Colitis and Crohn's Disease
- ClinicalTrials.gov ID
- NCT00619489
- Acronym / sponsor ID
- C13004
- Conditions
- Ulcerative Colitis, Crohn's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2007
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 21 Feb 2008 (estimated)
- Results
- Posted 18 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vedolizumab 2 mg/kg | Experimental | Drug: vedolizumabParticipants 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 | Drug: vedolizumabParticipants received vedolizumab, 6 mg/kg, IV, on Days 1, 15 and 43, and thereafter once every 8 weeks for up to 78 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (6 listed)
- Low lymphocyte counts
- History of imaging abnormalities, multiple sclerosis (MS), brain tumor or other neurological illness
- Active or recent serious infections
- Recent treatment with biologic (i.e., Remicade) or investigational drug
- Impending surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vedolizumabAlso: Entyvio, MLN0002, MLN02, LDP-02Vedolizumab for intravenous (IV) infusion | Drug | Vedolizumab 2 mg/kg, Vedolizumab 6 mg/kg |
Primary outcome
Number of Participants With Adverse Events (AEs)
Time frame: From Day 1 to Day 637
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.
Number of Participants With Clinically Significant Laboratory Findings
Time frame: through Day 637
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes in the blood.
Number of Participants With Signs and Symptoms of Progressive Multifocal Leukoencephalopathy (PML)
Time frame: through Day 637
At every visit, before receiving study treatment participants were evaluated by clinic staff for signs of PML using a PML symptom checklist.
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.
3 secondary outcomes
Serum Concentration of Vedolizumab Before Dosing
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
Time frame: Days 43, 99, 155 and 267, predose
Saturation of Receptors by Vedolizumab Before Dosing Using the MAdCAM-1-Fc Assay
Time frame: Days 43, 99, 155 and 267, predose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26893500Colombel 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vedolizumab in people with Ulcerative Colitis and Crohn's Disease, run by Millennium Pharmaceuticals, Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) (time frame: From Day 1 to Day 637). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00619489, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2014.