Clinical trial NCT00619489: Long Term Safety of Vedolizumab (MLN0002) in Patients With Ulcerative Colitis and Crohn's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Crohn's Disease
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-02-21
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From Day 1 to Day 637
measure: Number of Participants With Clinically Significant Laboratory Findings
timeFrame: through Day 637
measure: Number of Participants With Signs and Symptoms of Progressive Multifocal Leukoencephalopathy (PML)
timeFrame: through Day 637
measure: Number of Participants With Human Anti-human Antibodies (HAHA)
timeFrame: Samples collected prior to dosing on Days 1, 43, 155, 267, 379, 491, and 637.
Secondary outcomes:
measure: Serum Concentration of Vedolizumab Before Dosing
timeFrame: Days 43, 99, 155 and 267, predose
measure: Saturation of Receptors by Vedolizumab Before Dosing on Days 1, 43, 99, 155 and 267 by ACT-1 Assay
timeFrame: Days 43, 99, 155 and 267, predose
measure: Saturation of Receptors by Vedolizumab Before Dosing Using the MAdCAM-1-Fc Assay
timeFrame: Days 43, 99, 155 and 267, predose
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.