evaluation of safety, tolerability, and pk of vx15/2503 in patients with ms

Conditions: Multiple Sclerosis

Summary: 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.

Eligibility criteria:
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

Keywords: vx15/2503 semaphorin 4d sema4d cd100 safety tolerability pharmacokinetics immunogenicity multiple sclerosis monoclonal antibody