Clinical trial NCT01764737: Evaluation of Safety, Tolerability, and PK of VX15/2503 In Patients With MS
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: VX15/2503
Semaphorin 4D
SEMA4D
CD100
safety
tolerability
pharmacokinetics
immunogenicity
multiple sclerosis
monoclonal antibody
Lead sponsor: Vaccinex Inc.
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2013-01-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety/Tolerability as determined by number of patients with adverse events
timeFrame: Up to 12 weeks depending on dose cohort
Secondary outcomes:
measure: Half-life of VX15/2503
timeFrame: Up to 12 weeks depending on dose cohort
measure: Peak plasma concentration (Cmax) of VX15/2503
timeFrame: Up to 12 weeks depending on dose cohort
measure: Area under the plasma concentration versus time curve (AUC) of VX15/2503
timeFrame: Up to 12 weeks depending on dose cohort
measure: Number of patients who develop anti-drug antibody
timeFrame: Up to 12 weeks depending on dose cohort
Other outcomes:
measure: Cellular Semaphorin 4D (SEMA4D; CD100) percent saturation
timeFrame: Up to 12 weeks depending on dose cohort
measure: VX15/2503 dose level vs serum SEMA4D levels
timeFrame: Up to 12 weeks depending on dose cohort
measure: Change in magnetic resonance imaging (MRI) parameters as compared to VX15/2503 dose level
timeFrame: Screening to 4 weeks post-dose
measure: VX15/2503 dose vs the change in Kurtzke Expanded Disability Status Scale
timeFrame: Up to 12 weeks depending on dose cohort
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates, PC
state: Alabama
city: Aurora
country: United States
facility: University of Colorado Hospital, Aschutz Inpatient Pavilion
state: Colorado
city: Indianapolis
country: United States
facility: Indiana University Health Neuroscience Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Wayne State University - University Health Center
state: Michigan
city: Latham
country: United States
facility: MS Center of Northeastern NY/Empire Neurology
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: The Neurological Institute, PA
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Vaccinex Inc.
name: John Leonard, PhD
role: STUDY_DIRECTOR
affiliation: MS Center of Northeastern NY/Empire Neurology
name: Keith R Edwards, MD, FAAD
role: PRINCIPAL_INVESTIGATOR
affiliation: North Central Neurology Associates, PC
name: Christopher C LaGanke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Neurological Institute, PA
name: T H Rao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Lawrence M Samkoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Lael A Stone, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University - University Health Center
name: Omar Khan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kansas Medical Center
name: Sharon Lynch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University Health Neuroscience Center
name: David H Mattson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado Hospital, Anschutz Inpatient Pavilion
name: Timothy Vollmer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swedish Medical Center
name: Pavle Repovic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: LaGanke C, Samkoff L, Edwards K, Jung Henson L, Repovic P, Lynch S, Stone L, Mattson D, Galluzzi A, Fisher TL, Reilly C, Winter LA, Leonard JE, Zauderer M. Safety/tolerability of the anti-semaphorin 4D Antibody VX15/2503 in a randomized phase 1 trial. Neurol Neuroimmunol Neuroinflamm. 2017 Jun 16;4(4):e367. doi: 10.1212/NXI.0000000000000367. eCollection 2017 Jul.
citation: Worzfeld T, Offermanns S. Semaphorins and plexins as therapeutic targets. Nat Rev Drug Discov. 2014 Aug;13(8):603-21. doi: 10.1038/nrd4337.