VX15/2503 Treatment for Huntington's Disease
a study on Huntington's Disease
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.
A Phase 2, Multi-center, Randomized, Double-blind, Placebo Controlled Study in Subjects With Late Prodromal and Early Manifest Huntington's Disease (HD) to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of VX15/2503
VX15/2503-N-131 is a Phase 2, multi-center, 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). Efficacy endpoints include determining the effect of VX15/2503 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 VX15/2503 who volunteer will undergo a lumbar puncture at V13 to collect cerebral spinal fluid (CSF) to evaluate VX15/2503 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 VX15/2503 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.
Huntington's Disease Prodromal Stage Early Manifest Stage Huntington Disease VX15/2503
You can join if…
Open to people ages 21 years and up
- Male or female and are at least greater than or equal to 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 determined to have a clinical diagnosis of HD by the Site Investigator as defined by a DCL of 4.
- Must fulfill both of the following criteria at Screening:
- Have undergone genetic testing with a known CAG repeat greater than or equal to
- No features of juvenile HD (Westphal variant).
- If female must be either surgically sterile, postmenopausal, or nonlactating and nonpregnant. Female subjects of childbearing potential must practice a highly effective method of contraception.
- If male, must agree to use a reliable method of birth control (condoms with contraceptive foams or sexual abstinence) during the study and for 6 months after the last dose of study drug.
- Are willing and capable of providing informed consent for study participation, CAG genotyping (all subjects).
- Are capable of reading, writing, and communicating effectively with others.
- Are taking stable doses of any concomitant medications (including tetrabenazine and deutetrabenazine) during the 1 month prior to the Baseline Visit, with the exception of newly prescribed anxiolytics for the use of pre-medication prior to imaging at screening, which will be permitted on a case-by-case basis.
- Must meet all criteria required to move forward with the Randomization Authorization Flow (RAF) and be considered eligible by the RAF Reviewer.
You CAN'T join if...
- Have participated in an investigational drug or device study within 30 days of the Baseline Visit, or 180 days if previous investigational drug was a MAb therapeutic, or previously participated in SIGNAL Cohort A. This does not apply to Cohort B subjects who are being offered the option to participate in the extension of Cohort B.
- Have had previous neurosurgery for Huntington's disease or other movement disorders.
- Are a suicide risk, as determined by meeting any of the following criteria:
- suicide attempt within one year prior to Baseline.
- suicidal ideation as defined by a positive response to question 5 on the C-SSRS(Baseline visit form) suicidal ideation section, within 60 days of the Baseline Visit.
- significant risk of suicide, as judged by the site Investigator.
- Have marked cognitive impairment with a Montreal Cognitive Assessment (MoCA) Score less than or equal to 22.
- Have a presence of clinically significant psychosis and/or confusional states, in the opinion of the site Investigator.
- Have clinically significant laboratory or ECG abnormalities at Screening, in the opinion of the site Investigator.
- Have clinically relevant hematologic, hepatic, cardiac, or renal disease.
- Have a medical history of infection with human immunodeficiency virus, hepatitis C and/or hepatitis B, or found to have an abnormality at Screening.
- Have a history of substance abuse (based on DSMIV criteria) within the past 12 months prior to Screening.
- . If female are pregnant or breastfeeding.
- . Have a known allergy to any ingredient in the study drug.
- . Have a history of malignancy of any type within 2 years prior to Screening. A history of surgically excised non-melanoma skin cancers, and superficial bladder or prostate cancer is permitted.
- . Have a clinically significant medical, surgical, laboratory, or behavioral abnormality which in the judgment of the site Investigator makes the subject unsuitable for the study.
- . Have any significant findings not related to HD on the screening MRI which in the judgment of the site Investigator makes the subject unsuitable for the study.
- . Have any of the following conditions (which would exclude MRI participation):
- An implant/device/condition that is contraindicated for MRI (e.g. pacemaker,severe claustrophobia, prosthetic heart valve, any metal fragments in the eyes or body--in some cases, an X-ray may be needed before an MRI scan, to ensure it is safe to enter the scanner).
- Body habitus that would impede completion of MRI scan. (Subject weight above 158 kg should be discussed with the Medical Monitor).
NOTE: If PET is done on PET-MRI all the above conditions apply for PET-MRI.
- . Are undergoing FDG-PET and have received research-related radiation exposure that exceeds institutional guidelines in the prior year if applicable.
- . Are undergoing a LP for CSF collection and have any of the following conditions:uncorrected bleeding or clotting disorders, skin infections near the site of the LP,suspicion of increased intracranial pressure, allergies to numbing medications (local anesthetics), acute spinal trauma, history of migraines.
- . Are undergoing a LP for CSF collection and taking any of the following types of anticoagulants: coumarins and indandiones, Factor Xa inhibitors, heparins, or thrombin inhibitors.
- University of California, San Diego accepting new patients
La Jolla California 92037 United States
- University of California San Francisco accepting new patients
San Francisco California 94143 United States
- accepting new patients
- Start Date
- Completion Date
- Vaccinex Inc.
- Nonclinical research article: Anti-semaphorin 4D immunotherapy ameliorates neuropathology and some cognitive impairment in the YAC128 mouse model of Huntington disease.
- Phase 2
- Study Type
- Last Updated
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