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

• ClinicalTrials.gov Identifier: NCT01764737
• Recruitment Status: Completed
• First Posted: January 10, 2013
• Last Update Posted: February 6, 2015
• Sponsor: Vaccinex Inc.
• Collaborator: PRA Health Sciences
• Information provided by (Responsible Party): Vaccinex Inc.

Tracking Information

• First Submitted Date: January 3, 2013
• First Posted Date: January 10, 2013
• Last Update Posted Date: February 6, 2015
• Study Start Date: December 2012
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 7, 2013): Safety/Tolerability as determined by number of patients with adverse events [ Time Frame: Up to 12 weeks depending on dose cohort ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 7, 2013)

• Half-life of VX15/2503 [ Time Frame: Up to 12 weeks depending on dose cohort ]
• Peak plasma concentration (Cmax) of VX15/2503 [ Time Frame: Up to 12 weeks depending on dose cohort ]
• Area under the plasma concentration versus time curve (AUC) of VX15/2503 [ Time Frame: Up to 12 weeks depending on dose cohort ]
• Number of patients who develop anti-drug antibody [ Time Frame: Up to 12 weeks depending on dose cohort ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 7, 2013)

• Cellular Semaphorin 4D (SEMA4D; CD100) percent saturation [ Time Frame: Up to 12 weeks depending on dose cohort ]
• VX15/2503 dose level vs serum SEMA4D levels [ Time Frame: Up to 12 weeks depending on dose cohort ]
• Change in magnetic resonance imaging (MRI) parameters as compared to VX15/2503 dose level [ Time Frame: Screening to 4 weeks post-dose ]
  MRI parameters:

  • Number of T1 gadolinium (Gd)-enhancing lesions
  • Number of T2 lesions
  • Total volume of T1 and T2 lesions if the investigational site has the imaging processing capability
• VX15/2503 dose vs the change in Kurtzke Expanded Disability Status Scale [ Time Frame: Up to 12 weeks depending on dose cohort ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

• Drug: VX15/2503
  single dose intravenous administration
• Drug: Placebo
  single dose intravenous administration

Study Arms

• Experimental: VX15/2503
  Intervention: Drug: VX15/2503
• Experimental: Placebo
  Intervention: Drug: Placebo

Publications *

• 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.
• Worzfeld T, Offermanns S. Semaphorins and plexins as therapeutic targets. Nat Rev Drug Discov. 2014 Aug;13(8):603-21. doi: 10.1038/nrd4337.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 7, 2013): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01764737
• Other Study ID Numbers: VX15/2503-N-101
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Vaccinex Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Vaccinex Inc.
• Original Study Sponsor: Same as current
• Collaborators: PRA Health Sciences

Investigators

• Study Director: John Leonard, PhD; Vaccinex Inc.
• Principal Investigator: Keith R Edwards, MD, FAAD; MS Center of Northeastern NY/Empire Neurology
• Principal Investigator: Christopher C LaGanke, MD; North Central Neurology Associates, PC
• Principal Investigator: T H Rao, MD; The Neurological Institute, PA
• Principal Investigator: Lawrence M Samkoff, MD; University of Rochester
• Principal Investigator: Lael A Stone, MD; The Cleveland Clinic
• Principal Investigator: Omar Khan, MD; Wayne State University - University Health Center
• Principal Investigator: Sharon Lynch, MD; University of Kansas Medical Center
• Principal Investigator: David H Mattson, MD; Indiana University Health Neuroscience Center
• Principal Investigator: Timothy Vollmer, MD; University of Colorado Hospital, Anschutz Inpatient Pavilion
• Principal Investigator: Pavle Repovic, MD; Swedish Medical Center

• PRS Account: Vaccinex Inc.
• Verification Date: February 2015