Evaluation of Safety, Tolerability, and PK of VX15/2503 In Patients With MS

A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study Of The Safety, Tolerability, And Pharmacokinetics Of Intravenous VX15/2503 In Patients With Multiple Sclerosis

The purpose of this study is to evaluate the safety and tolerability of IV administration of VX15/2503 in patients with multiple sclerosis. The escalation part of the study will determine the maximum tolerated dose (MTD) or the Maximum Administered Dose if no MTD is found.

VX15/2503-N-101 is a single ascending dose-escalation, randomized, double-blinded, placebo-controlled study to evaluate the safety and tolerability of IV-administered VX15/2503 in patients with multiple sclerosis. This will be accomplished by using a dose escalation procedure starting at a low dose of VX15/2503 and will continue based on predefined parameters until the maximum tolerated dose is identified. Patients will be randomized at a 4:1 ratio to receive VX15/2503 to placebo. The patients and the study team will be blinded to the treatment that each patient receives.

The study drug, VX15/2503, is a humanized monoclonal antibody that binds to the semaphorin 4D (SEMA4D; CD100) antigen. Experimental evidence suggest that antibody neutralization of SEMA4D may represent a new therapeutic strategy for treating multiple sclerosis.

Inclusion Criteria:

• Patients 18-60 years of age who have been diagnosed with MS for at least 1 year as defined by the 2010 revisions to the McDonald criteria
• Has an EDSS score of 0 to 6.5 inclusive at screening
• Has a body mass index of 18 to 32 kg/m2
• Is willing to undergo and has no contraindications to brain MRI
• Willing to use a medically acceptable method of contraception throughout the study period and for 6 months after the dose of VX15/2503, unless patient is surgically sterile or postmenopausal. Women of childbearing potential must have started using adequate contraception at least 2 months before the Day 1 visit.
• Male patients must agree to defer from donating sperm for 6 months after VX15/2503 administration
• Women of childbearing potential must have a negative serum pregnancy test at screening, which will be confirmed at baseline using a urine test before administration of VX15/2503
• Is willing to forego other forms of experimental treatment during the study

Exclusion Criteria:

• Had an MS relapse that did not stabilize within the 30 days before the start of screening.
• Has any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic/gynecologic, pulmonary, neurologic, psychiatric, or renal conditions; has a history of relevant clinically significant allergic or anaphylactic reactions; or has any other clinically significant major disease that, as assessed by the investigator, would pose a risk to patient safety or interfere with the study evaluations, procedures, or completion
• Has any clinically significant laboratory value outside the normal range for MS patients at screening, or has abnormal hematologic, renal, or hepatic function based on laboratory tests
• Is a pregnant or breastfeeding woman
• Has received treatment with any MS disease-modifying therapy other than interferon beta or glatiramer acetate within 3 months prior to dosing
• Has been treated with natalizumab, daclizumab, or fingolimod for any indication within 6 months prior to dosing
• Has had any prior treatment with alemtuzumab, rituximab, mitoxantrone, total lymphoid irradiation, bone marrow transplantation, or T cell or T cell receptor vaccination
• Has received any experimental agent within 6 months prior to dosing, or within a period equivalent to 5 half-lives of the agent (whichever is longer); or is currently involved in any other research study
• Has undergone any major surgical procedure within the 4 weeks prior to dosing
• Has a history of congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to dosing
• Has a clinically significant ECG finding at screening
• Has a known or suspected human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Has a known or suspected allergy to Gd or other contraindication to brain MRI
• Has a history of an opportunistic infection or a history of acute infection requiring systemic antibiotics, antivirals, or antifungals within 6 weeks prior to dosing (antiinfective therapy must have been completed at least 4 weeks prior to dosing)
• Has any other intercurrent illness or condition, including alcohol or drug dependence as determined by the investigator, which could impact the patient's compliance with or ability to complete the study
• History of seizure disorder or unexplained blackouts or history of seizure within 3 months of screening
• History of suicidal ideation within 3 months prior to screening, episode of severe depression within 3 months prior to screening
• Has a sensitivity to VX15/2503 or the ingredients or excipients of VX15/2503, or known or suspected sensitivity to mammalian cell-derived products
• Has donated or lost more than 1 unit of blood in the 60 days prior to screening