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

NCT01764737 | Completed Phase 1

• 1 other identifier: VX15/2503-N-101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 10

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.

Conditions

Multiple Sclerosis

Keywords

VX15/2503; Semaphorin 4D; SEMA4D; CD100; safety; tolerability; pharmacokinetics; immunogenicity; multiple sclerosis; monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Safety/Tolerability as determined by number of patients with adverse events

  Up to 12 weeks depending on dose cohort

Secondary Outcomes (4)

• Half-life of VX15/2503

  Up to 12 weeks depending on dose cohort

• Peak plasma concentration (Cmax) of VX15/2503

  Up to 12 weeks depending on dose cohort

• Area under the plasma concentration versus time curve (AUC) of VX15/2503

  Up to 12 weeks depending on dose cohort

• Number of patients who develop anti-drug antibody

  Up to 12 weeks depending on dose cohort

Other Outcomes (4)

• Cellular Semaphorin 4D (SEMA4D; CD100) percent saturation

  Up to 12 weeks depending on dose cohort

• VX15/2503 dose level vs serum SEMA4D levels

  Up to 12 weeks depending on dose cohort

• Change in magnetic resonance imaging (MRI) parameters as compared to VX15/2503 dose level

  Screening to 4 weeks post-dose

Study Arms (2)

VX15/2503

EXPERIMENTAL

Drug: VX15/2503

Placebo

EXPERIMENTAL

Drug: Placebo

Interventions

VX15/2503 DRUG

single dose intravenous administration

VX15/2503

Placebo DRUG

single dose intravenous administration

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vaccinex Inc.: lead
• PRA Health Sciences: collaborator

Study Sites (10)

North Central Neurology Associates, PC

Cullman, Alabama, 35058, United States

Location

University of Colorado Hospital, Aschutz Inpatient Pavilion

Aurora, Colorado, 80045, United States

Location

Indiana University Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Wayne State University - University Health Center

Detroit, Michigan, 48201, United States

Location

MS Center of Northeastern NY/Empire Neurology

Latham, New York, 12110, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

The Neurological Institute, PA

Charlotte, North Carolina, 28204, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

Related Publications (2)

• 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.

  PMID: 28642891 DERIVED

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

  PMID: 25082288 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• John Leonard, PhD

  Vaccinex Inc.

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2013
• First Posted: January 10, 2013
• Study Start: December 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: February 6, 2015

Record last verified: 2015-02

Locations

US (10)