A Study in Subjects With Late Prodromal & Early Manifest HD to Assess the Safety, Tolerability, pk, and Efficacy of Pepi
- Registration Number
- NCT02481674
- Lead Sponsor
- Vaccinex Inc.
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, PK, and efficacy of Pepinemab in subjects with late prodromal and early manifest Huntington's disease.
- Detailed Description
VX15/2503-N-131 (SIGNAL-HD) is a Phase 2, multi-center, randomized, double-blind, placebo controlled study of VX15/2503 (pepinemab) in subjects with late prodromal and early manifest Huntington's disease. The primary objective is to evaluate the safety and tolerability of monthly IV administration of a single dosage of pepinemab (or placebo). Efficacy endpoints include determining the effect of pepinemab on brain volumes (MRI), FDG-PET imaging, 11C-PBR28 (TSPO) PET imaging (subset of Cohort B only) and clinical features of HD including cognition, motor function, behavior, functional abilities, global function and global measurement of change. Additional endpoints include PK / PD, immunogenicity, and exploratory biomarkers. Subjects in Cohort B that have received 12 months of pepinemab who volunteer will undergo a lumbar puncture at V13 to collect cerebral spinal fluid (CSF) to evaluate pepinemab mAb concentrations, total sSEMA4D levels, and other biomarkers in their CSF. Enrollment will involve approximately 276 individuals who are 21 years of age or older with late prodromal (CAG-age product score (CAP score) of greater than 200 and Diagnostic Confidence Level (DCL) of 2 or 3) or early manifest HD (Total Functional Capacity (TFC) greater than or equal to 11). The study will be divided into Cohort A and Cohort B. Cohort A is now complete and an unblinded analysis has been performed. Cohort A subjects were treated for 6 months with either drug or placebo (1:1) and then all subjects were treated with drug for 6 months, followed by 3 months of follow up. Treatment duration for each subject in Cohort A was 12 months. Participation in Cohort A included a Screening visit, a Baseline visit within 30 days of screening; 12 monthly treatment visits beginning at baseline and continuing through Month 12; follow-up safety phone call at one month and a follow-up safety visit three months after the final infusion. Cohort A subjects participated in the study for approximately 16 months. Based on the analysis of Cohort A, it was decided to extend the duration of treatment for a subset of subjects in Cohort B to evaluate the clinical response to pepinemab after 36 months. Additional enrolled subjects in Cohort B will be treated with drug or placebo (1:1). Participation in Cohort B will include a Screening visit, a Baseline visit within 30 days of screening; 18 or 36 monthly visits beginning at baseline and continuing through Month 18 or Month 36; follow-up safety phone call or visit, and for a subset of subjects, a follow-up safety visit three and six months after the final infusion. Cohort B subjects will participate in the study for approximately 19 and up to 37 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 301
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo A placebo control will be administered via monthly intravenous infusions VX15/2503 VX15/2503 The study drug VX15/2503 will be administered via monthly intravenous infusions
- Primary Outcome Measures
Name Time Method Revisions to SAP were made prior to un-blinding, on June 30, 2020, upon consultation with FDA. Prior to DBL/Study Completion If primary outcome, listed below (Outcome 3), does not reach its critical p-value, the secondary outcomes will not be formally tested. If both co-primary outcomes are statistically significant, the five secondary outcomes will be formally tested following a hierarchical testing procedure.
Efficacy of monthly IV administration of pepinemab relative to placebo in Early Manifest HD (Cohort B1) Up to 18 months Co-primary outcome measured by the change from baseline in the Huntington's Disease Two-item Cognitive Family (PTAP and OTS) selected from the Huntington's Disease
Safety and tolerability of monthly intravenous (IV) administration of pepinemab relative to placebo in subjects with early HD (Cohort B pooled, includes Cohort B1 Early Manifest and Cohort B2 Late Prodromal HD). Up to 18 months Measured by drug related adverse event frequency and laboratory test abnormalities in all subjects.
- Secondary Outcome Measures
Name Time Method Clinical feature of Early Manifest HD: motor function (Q-Motor) Up to 18 months Measured by change from baseline of Q-Motor Tap Speed IOI duration mean in Cohort B1
Clinical feature of Early Manifest HD: functional capacity (UHDRS-TFC) Up to 18 months Measured by change from baseline of UHDRS-TFC score in Cohort B1
Clinical Feature of Early HD: cognition (Huntington's Disease Two-item Cognitive Family). Up to 18 months Measured by change from baseline in the two-item HD-CAB family (PTAP and OTS) in Cohort B pooled
Clinical feature of Early HD: functional capacity (UHDRS-TFC) Up to 18 months Measured by time to 1-point change in UHDRS-TFC score in Cohort B pooled
Clinical Feature of Early HD: motor function (Q-Motor) Up to 18 months Measured by change from baseline of Q-Motor Tap Speed IOI duration mean in Cohort B pooled
Trial Locations
- Locations (31)
University of Vermont
🇺🇸Burlington, Vermont, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Charlestown, Massachusetts, United States
University of Florida Gainesville
🇺🇸Gainesville, Florida, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Columbia University
🇺🇸New York, New York, United States
University of Alberta
🇨🇦Edmonton, Alberta, Canada
University of British Columbia
🇨🇦Vancouver, British Columbia, Canada
University of Washington
🇺🇸Seattle, Washington, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Rochester
🇺🇸Rochester, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Texas Houston Medical School
🇺🇸Houston, Texas, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
University of Washington and VA Puget Sound Health Care System
🇺🇸Seattle, Washington, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Colorado - Denver
🇺🇸Aurora, Colorado, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Duke University Health Center
🇺🇸Durham, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Centre hospitalier de l'Université de Montréal (CHUM)
🇨🇦Montréal, Quebec, Canada
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States