Long Term Safety of Vedolizumab (MLN0002) in Patients With Ulcerative Colitis and Crohn's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00619489
First received: February 11, 2008
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Crohn's Disease
Drug: vedolizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: From Day 1 to Day 637 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serum Concentration of Vedolizumab Before Dosing [ Time Frame: Days 43, 99, 155 and 267, predose ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Saturation of Receptors by Vedolizumab Before Dosing Using the MAdCAM-1-Fc Assay [ Time Frame: Days 43, 99, 155 and 267, predose ] [ Designated as safety issue: No ]
    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.


Enrollment: 72
Study Start Date: December 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: vedolizumab
Vedolizumab for intravenous (IV) infusion
Other Names:
  • Entyvio
  • MLN0002
  • MLN02
  • LDP-02
Experimental: 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.
Drug: vedolizumab
Vedolizumab for intravenous (IV) infusion
Other Names:
  • Entyvio
  • MLN0002
  • MLN02
  • LDP-02

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619489

Locations
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00619489     History of Changes
Other Study ID Numbers: C13004, U1111-1156-8608
Study First Received: February 11, 2008
Results First Received: June 19, 2014
Last Updated: June 19, 2014
Health Authority: Canada: Health Canada
Russia: Pharmacological Committee, Ministry of Health

Additional relevant MeSH terms:
Crohn Disease
Colitis
Ulcer
Colitis, Ulcerative
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colonic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 30, 2014