SIGNAL: A new investigational approach to early treatment of Huntington’s disease

Vaccinex and the Huntington Study Group (HSG) launched a trial for people with the gene mutation that causes HD who are either early in the progression of the disease or are not yet diagnosed with the disease.

The SIGNAL trial is designed to assess the safety, tolerability, and effectiveness of VX15, a novel monoclonal antibody, in people with late prodromal (not yet diagnosed) or early manifest (early in the progression of the disease) HD. It is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study being conducted at approximately 30 sites across the United States and Canada. The trial seeks to enroll a total of 240 individuals, 21 or older.

The trial has two cohorts. Cohort A, which consisted of the trial’s first 36 participants, is now complete. Those participants were treated for six months with either drug or placebo (1:1); then all participants were treated with study drug for six months, followed by three months of follow up.

Enrollment in Cohort A is now complete. To view the press release from Vaccinex, click here. To view a press release from Vaccinex about preliminary imaging data from Cohort A, click here. To view the HDSA webinar by Vaccinex President & CEO Maurice Zauderer, click here.

Currently, the SIGNAL trial is enrolling Cohort B participants who will be treated monthly with study drug or placebo (1:1) for 18 months and will take part in safety follow-up visits for up to six months after the final treatment.

The investigational compound being studied in the trial is VX15, a monoclonal antibody. This is a different class of drug than any other drug used in previous HD clinical trials. Monoclonal antibodies are more specific than most other drugs because they bind to and neutralize their desired target with high specificity. Previous nonclinical research and the results of Cohort A (see HDSA webinar regarding interim results by clicking here) suggest that VX15 may have the potential to slow the progression of brain inflammation, which has been shown to impair thinking, movement, and behavior in HD animal models.

VX15 has not been approved by the FDA; its potential benefits for HD are being investigated within the SIGNAL trial.

The VX15 antibody is designed to bind specifically to the semaphorin 4D (SEMA4D) protein, a molecule that guides the activation and movement of cells within the body. In HD, VX15 has the potential to block SEMA4D, which may be responsible for inflammation in the brains of individuals who develop HD. Reducing brain inflammation may slow HD’s subsequent effects, including impaired cognition, movement, and behavior.

The Cohort B study procedures involve:

  • A screening visit to confirm eligibility. Approved subjects will complete a baseline visit and then begin the investigational period
  • Once a month study drug or placebo delivery through an intravenous infusion that takes at least one hour
  • Brain imaging and cognitive testing during specified visits – these monthly visits may take a full day to complete
  • Lumbar puncture for collection of cerebrospinal fluid on one occasion for subjects in Cohort B who volunteer
  • Safety, tolerability, and efficacy assessments will be performed at all visits
  • Participants will be treated with study drug or placebo intravenous infusion for 18 months and will take part in safety follow-up visits for up to six months after the final treatment

SIGNAL participants may enroll in observational studies, but they cannot participate in other clinical trials of investigational compounds while they are participating in SIGNAL. However, SIGNAL study participants may be eligible for other clinical studies once they complete the SIGNAL trial.

Participants may still be eligible for SIGNAL if they are taking other prescribed medications that are FDA approved.

If you or someone close to you is interested in taking part in SIGNAL, or if you would like additional information or have questions regarding the study, please contact a site near you (see the list of participating sites below) or the Huntington Study Group at 1-800-487-7671 or info@hsglimited.org.

Participating sites and contact information:

Beth Israel Deaconess Medical Center

Boston, MA

Jaqueline Fung, coordinator

 jfung@bidmc.harvard.edu

 (617) 975-7636

 

Columbia University Medical Center

New York, NY

Paula Wasserman, coordinator

 pl2032@cumc.columbia.edu

 (212) 305-4597

 

Duke University

Durham, NC

Kate Beck, coordinator

 Kate.beck@duke.edu

 (919) 668-2278

 

Emory University School of Medicine

Atlanta, GA

Elaine Sperin, coordinator

 esperin@emory.edu

 (404) 712-7044

 

Georgetown University

Washington, DC

Robin Kuprewicz, coordinator

 rk1028@georgetown.edu

 (202) 687-6419

 

Indiana University School of Medicine

Indianapolis, IN

Andrea Hurt, coordinator

 andhurt@iupui.edu

 (317) 963-7449

 

Huntington’s Disease Center at Johns Hopkins

Baltimore, MD

Mollie Jenckes, coordinator

 mjenckes@jhmi.edu

 (410) 294-6503

 

Massachusetts General Hospital

Boston, MA

Keith Malarick, coordinator

 kmalarick@partners.org

 (617) 726-5892

 

Ohio State University

Columbus, OH

Allison Daley, coordinator

 allison.daley@osumc.edu

 (614) 688-8672

 

University of Alabama at Birmingham

Birmingham, AL

Jenna Smith, coordinator

 jennat@uab.edu

 (205) 996-2807

 

University of Alberta

Edmonton, Alberta

Paul McCann, coordinator

 paul.mccann@ahs.ca

 (780) 407-1614

 

University of British Columbia

Vancouver, BC

Tuan Lee, coordinator

 tle@cmmt.ubc.ca

 (604) 822-4872

 

University of California, San Diego

San Diego, CA

Sungmee Park, coordinator

Sup035@ucsd.edu

(858) 249-0568

 

University of California, San Francisco

San Francisco, CA

Nancy Cai, coordinator

nancy.cai@ucsf.edu

(415) 502-7640

 

University of Cincinnati

Cincinnati, OH

Brandi Crews, coordinator

 brandi_crews@uc.edu

 (513) 558-6275

 

University of Colorado

Aurora, CO

Mary Cook, coordinator

 mary.m.cook@ucdenver.edu

 (303) 724-7968

 

University of Iowa

Iowa City, IA

Owen Wade, coordinator

 owen-wade@uiowa.edu

 (319) 353-5336

 

University of Louisville

Louisville, KY

Annette Robinson, coordinator

 annette.robinson@louisville.edu

 (502) 540-3585

 

University of Michigan

Ann Arbor, MI

Angela Stovall, coordinator

 astovall@med.umich.edu

 (734) 647-4787

 

University of Rochester

Rochester, NY

Amy Chesire, coordinator

 amy_chesire@urmc.rochester.edu

 (585) 341-7519

 

University of Texas Health Science Center at Houston

Houston, TX

Jamie Sims, coordinator

 jamie.sims@uth.tmc.edu

 (832) 325-7107

 

University of Toledo

Toledo, OH

Julia Spears, coordinator

 julia.spears@utoledo.edu

 (419) 383-6728

 

University of Vermont

Burlington, VT

Emily Houston, coordinator

 emily.houston@uvm.edu

 (802) 656-8989

 

University of Washington

Seattle, WA

Debra Del Castillo, coordinator

 debradel@uw.edu

 (206) 543-3647

 

Vanderbilt University

Nashville, TN

Danielle Buchanan, coordinator


danielle.a.buchanan@vumc.org

(615) 875-3274

 

Virginia Commonwealth University

Richmond, VA

Heather Ward, coordinator

heather.d.librand@vcuhealth.org

(434) 996-7162

 

Wake Forest University

Winston Salem, NC

Christine O’Neill, coordinator

 coneill@wakehealth.edu

 (336) 716-8611

 

Washington University

St. Louis, MO

Melissa Ammel, coordinator

 ammelm@neuro.wustl.edu

 (314) 747-3470