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

Vaccinex

Status and phase

Completed

Phase 1

Conditions

Multiple Sclerosis

Treatments

Drug: Placebo

Drug: VX15/2503

Study type

Interventional

Funder types

Industry

Identifiers

NCT01764737

VX15/2503-N-101

Details and patient eligibility

About

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.

Full description

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.

Enrollment

50 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

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