Purpose of Study: The purpose of this study is to evaluate the safety, tolerability, PK and efficacy of VX15/2503 in subjects with late-prodromal and early-manifest Huntington's disease.
Description of Study: VX15/2503-N-131 is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study of VX15/2503 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 VX15/2503 (or placebo). Secondary objectives include determining the effect of VX15/2503 on brain volumes (MRI), FDG-PET imaging and clinical features of HD including cognition, motor function, behavior, functional abilities and global function. Additional secondary objectives include PK / PD, immunogenicity and exploratory biomarkers.
Enrollment will involve approximately 84 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 subjects will be treated for six months with either drug or placebo (1:1), and then all subjects will be treated with drug for six months, followed by three months of follow up. Treatment duration for each subject will be 12 months. Participation in Cohort A will include a screening visit, a baseline visit within 30 days of screening, 12 monthly treatment visits beginning at baseline and continuing through month 12, a follow-up safety phone call at one month and a follow-up safety visit three months after the final infusion. Cohort A subjects will participate in the study for approximately 16 months.
Cohort B subjects will be treated with drug or placebo (1:1) for 18 months, followed by three months of follow up. Treatment duration for each subject will be 18 months. (The duration of treatment may be reduced to 12 months based on the outcome of the analysis of the data from Cohort A.) Participation in Cohort B will include a screening visit, a baseline visit within 30 days of screening, 18 monthly treatment visits beginning at baseline and continuing through month 18, a follow-up safety phone call at one month and a follow-up safety visit three months after the final infusion. Cohort B subjects will participate in the study for approximately 22 months.
Eligibility Criteria: Male or female at least 21 years of age at screening.
Must fulfill one of the following criteria at screening:
- Late-prodromal HD as defined by a CAP score of greater than 200 and DCL 2 or 3,
- Early-manifest HD as defined by a TFC greater than or equal to 11. Subject must have been given a clinical diagnosis of HD
Must fulfill both of the following criteria at screening:
- Have undergone genetic testing with a known CAG repeat greater than or equal to 36
- Have no features of juvenile HD (Westphal variant).
Females must be either surgically sterile, postmenopausal or nonlactating and nonpregnant. Female subjects of childbearing potential must practice a highly effective method of contraception
Males must agree to use a reliable method of birth control
Subjects are willing and capable of providing informed consent for study participation and CAG genotyping (all subjects)
Subjects are capable of reading, writing and communicating effectively with others
Subjects are taking stable doses of any concomitant medications (including tetrabenazine) during the month prior to the baseline visit, and dosing must remain stable throughout the study.
Status of Study: Recruiting
Principal Investigator: Sandra Kostyk, MD, PhD
Allison Daley, MS, MPH
Phone: 614-688-8672, Fax: 614-366-8672
Sponsor: Vaccinex, Inc.
Collaborator: Huntington Study Group