Study of Vedolizumab Following Multiple Intravenous Doses in Patients With Ulcerative Colitis

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

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).

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.

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