Clinical trial NCT01177228: Study of Vedolizumab Following Multiple Intravenous Doses in Patients With Ulcerative Colitis
Official title: A Phase 2, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MLN0002 Following Multiple Intravenous Doses in Patients With Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-08-06
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study.

* Males or non-pregnant, non-lactating females voluntarily able to give informed consent
* All patients must agree to use 2 effective forms of contraception from screening to the end of the study
* Negative surveillance colonoscopy within the last 6 months if indicated by standard clinical practice guidelines
* Confirmed and active ulcerative colitis (UC)

  * Partial Mayo Score 1 - 7
  * Disease involvement extending proximal to the rectum
* May be receiving a therapeutic dose of conventional therapies for UC as defined by the protocol

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study.

* Patients who require ulcerative colitis (UC) surgical intervention or for whom surgical intervention is anticipated during the study
* Patients who fail to meet laboratory values as specified in the protocol or have a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist during the screening period
* Low-grade dysplasia, high-grade dysplasia, dysplasia-associated lesion or mass, or colorectal cancer
* Treatment with cyclosporine, FK506 (tacrolimus) or infliximab within 60 days prior to study
* Patients receiving any of the following within 14-days prior to the study: antibiotics for treatment of irritable bowel syndrome, heparin or warfarin, narcotics, tube feeding, defined formula diets or parenteral alimentation
* Colostomy, fistulae or known fixed symptomatic stenosis of the intestine
* Immunologic or ischemic intestinal condition
* Toxic megacolon
* Chronic hepatitis B or C or human immunodeficiency virus (HIV) infection
* Any vaccinations within 30 days prior to study drug administration
* History of imaging abnormalities, multiple sclerosis (MS), brain tumor or neurodegenerative disease
* Significantly impaired liver or renal function
* Current or recent history of alcohol dependence
* Current use of illicit drugs
* Active or recent serious infections or serious underlying disease as specified in protocol
* Active psychiatric problems that might interfere with compliance to study
* Previous exposure to MLN0002
* Participated in an investigational study within 30 days prior to study drug administration or received treatment with an investigational monoclonal antibody within the last 6 months

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From the first date of study drug administration through Day 253
measure: Cmax: Maximum Observed Plasma Concentration of Vedolizumab on Days 1 and 85
timeFrame: Days 1 and 85, prior to and 2, 12, 24, 48, and 72 hours after dosing.
measure: Cmin: Minimum Observed Plasma Concentration of Vedolizumab
timeFrame: Day 85, prior to and 2, 12, 24, 48, and 72 hours after dosing.
measure: Area Under the Plasma Concentration-Time Curve (AUC) for Vedolizumab
timeFrame: Days 0-14, Days 85-99, Days 85-141
measure: Terminal Phase Elimination Half-life (t½) of Vedolizumab
timeFrame: Pre-dose through Day 253
measure: Maximum Drug Effect (Emax) of Vedolizumab as Measured by Percent Inhibition of the Act-1 Marker
timeFrame: 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
measure: Maximum Drug Effect (Emax) as Measured by Inhibition of the MAdCAM-1-Fc Marker
timeFrame: 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
measure: Area Under the Drug Effect Time Curve [AUEC(0-last)] as Measured by Inhibition of the ACT-1 Marker
timeFrame: 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
measure: Area Under the Drug Effect Time Curve [AUEC(0-last)] as Measured by Inhibition of the MAdCAM-1-Fc Marker
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
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.
citation: Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20.