SIGNAL: A new investigational approach to early treatment of Huntington’s disease
Vaccinex and the Huntington Study Group (HSG) launched a new 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 or early manifest Huntington’s disease (HD). It is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study at 20 sites across the United States that seeks to enroll approximately 116 individuals, 21 or older, who are either early in the progression of the disease or are not yet diagnosed with the disease.
The investigational compound that will be 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 only bind to and neutralize their desired target. Previous research suggests 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 respond 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 study procedures involves:
- A screening visit to confirm eligibility. Approved subjects will complete a baseline visit and then begin the investigational period
- Once a month drug or placebo delivery through an approximately hour-long intravenous infusion
- 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 for subjects in Cohort B who volunteer
- Safety, tolerability, and efficacy assessments will be performed at all visits
- Subjects will be treated with drug or placebo intravenous infusion for 12-18 months
- Cohort A will receive drug or placebo for six months and then for the next six months, all participants will receive drug. (Enrollment in Cohort A is now complete. To view the press release from Vaccinex, click here. To view press release from Vaccinex about preliminary imaging data from Cohort A, click here.)
- Cohort B will receive drug or placebo for 18 months.
- A follow-up period includes a follow-up safety phone call at one month and a follow-up safety visit at three months after the final infusion.
SIGNAL participants may enroll in observational studies, but they cannot participate in other clinical trials of investigational compounds. Participants may still be eligible for SIGNAL if they are taking other prescribed medications.
To participate, you must visit your chosen site on a monthly basis during the trial period.
Participating sites and contact information:
Columbia University Medical Center
New York, NY
Paula Wasserman, coordinator
Peggy Perry-Trice, coordinator
Emory University School of Medicine
Elaine Sperin, coordinator
Hope Heller, coordinator
Massachusetts General Hospital
Keith Malarick, coordinator
Ohio State University
Allison Daley, coordinator
University of Alabama at Birmingham
Jenna Smith, coordinator
University of California, San Diego
San Diego, CA
Andrew Herndon, coordinator
University of Cincinnati
Hilary Perez, coordinator
University of Colorado
Mary Cook, coordinator
University of Iowa
Iowa City, IA
Amanda Miller, coordinator
University of Louisville
Annette Robinson, coordinator
University of Michigan
Ann Arbor, MI
Elizabeth Sullivan, coordinator
University of Rochester
Amy Chesire, coordinator
University of Toledo
Julia Spears, coordinator
University of Vermont
Emily Houston, coordinator
Philip Siragusa, coordinator
Wake Forest University
Winston Salem, NC
Christine O’Neill, coordinator
St. Louis, MO
Patricia Deppen, coordinator
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 or the Huntington Study Group at 1-800-487-7671 or email@example.com.
Listen to Dr. Andy Feigin, principal investigator, talk about the SIGNAL trial on Help4HD’s radio blog on the Aug. 14, 2015, episode.