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

Phase 1
Completed
Conditions
Multiple Sclerosis
Interventions
Drug: Placebo
Registration Number
NCT01764737
Lead Sponsor
Vaccinex Inc.
Brief 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.

Detailed 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VX15/2503VX15/2503-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Safety/Tolerability as determined by number of patients with adverse eventsUp to 12 weeks depending on dose cohort
Secondary Outcome Measures
NameTimeMethod
Half-life of VX15/2503Up to 12 weeks depending on dose cohort
Peak plasma concentration (Cmax) of VX15/2503Up to 12 weeks depending on dose cohort
Area under the plasma concentration versus time curve (AUC) of VX15/2503Up to 12 weeks depending on dose cohort
Number of patients who develop anti-drug antibodyUp to 12 weeks depending on dose cohort

Trial Locations

Locations (10)

Wayne State University - University Health Center

🇺🇸

Detroit, Michigan, United States

University of Colorado Hospital, Aschutz Inpatient Pavilion

🇺🇸

Aurora, Colorado, United States

North Central Neurology Associates, PC

🇺🇸

Cullman, Alabama, United States

Indiana University Health Neuroscience Center

🇺🇸

Indianapolis, Indiana, United States

MS Center of Northeastern NY/Empire Neurology

🇺🇸

Latham, New York, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

The Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

The Neurological Institute, PA

🇺🇸

Charlotte, North Carolina, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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