VX15/2503 Treatment for Huntington's Disease

a study on Huntington's Disease

Summary

for people ages 21 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

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.

Official Title

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

Details

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 240 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 (the 53 subjects enrolled prior to Amendment 4) to evaluate the clinical response to VX15/2503 after 36 months of treatment. Subjects enrolled in Cohort B prior to Amendment 4 (53 subjects) will be treated with drug or placebo (1:1) for 36 months, followed for 3 or 6 months off study drug. Subsequently, additional enrolled subjects in Cohort B will be treated with drug or placebo (1:1) for 18 months, followed for up to 6 months off study drug. Participation in Cohort B will include a Screening visit, a Baseline visit within 30 days of screening; 18 or 36 monthly treatment visits beginning at baseline and continuing through Month 18 or Month 36; follow-up safety phone call at one month and a follow-up safety visit three and possibly 6 months after the final infusion. Cohort B subjects will participate in the study for approximately 22 and up to 47 months.

Keywords

Huntington's Disease Prodromal Stage Early Manifest Stage Huntington Disease VX15/2503

Eligibility

You can join if…

Open to people ages 21 years and up

Highlights:

  1. Male or female and are at least greater than or equal to 21 years of age at Screening.
  2. Must fulfill one of the following criteria at Screening:
  3. Late prodromal HD as defined by a CAP score of greater than 200 and DCL 2 or 3.
  4. 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.
  5. Must fulfill both of the following criteria at Screening:
  6. Have undergone genetic testing with a known CAG repeat greater than or equal to
  7. .
  8. No features of juvenile HD (Westphal variant).
  9. 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.
  10. If male must agree to use a reliable method of birth control.
  11. Are willing and capable of providing informed consent for study participation, CAG genotyping (all subjects).
  12. Are capable of reading, writing, and communicating effectively with others.
  13. Are taking stable doses of any concomitant medications (including tetrabenazine)during the 1 month prior to the Baseline Visit and dosing must remain stable during the duration of the study.
  14. Must meet all criteria required for the Randomization Authorization Flow (RAF) and be considered eligible by the RAF Reviewer.

You CAN'T join if...

Highlights:

  1. 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.This does not apply to subjects who are being offered the option to participate in the extension of Cohort B.
  2. Have had previous neurosurgery for HD or other movement disorders.
  3. Are a suicide risk.
  4. Have marked cognitive impairment with a Montreal Cognitive Assessment (MoCA) Score less than or equal to 22.
  5. Have a presence of clinically significant psychosis and/or confusional states
  6. Have clinically significant laboratory or ECG abnormalities at Screening
  7. Have clinically relevant hematologic, hepatic, cardiac, or renal disease.
  8. Have a medical history of infection with human immunodeficiency virus, hepatitis C,and/or hepatitis B.
  9. Have a history of substance abuse (based on DSMIV criteria) within the past 12 months prior to Screening.
  10. . If female are pregnant or breastfeeding.
  11. . Have a known allergy to any ingredient in the study drug.
  12. . 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.
  13. . Have a clinically significant medical, surgical, laboratory, or behavioral abnormality which in the judgment of the investigator makes the subject unsuitable for the study.
  14. . Have any significant findings not related to HD on the screening MRI which in the judgment of the investigator makes the subject unsuitable for the study.
  15. . Have any of the following conditions (which would exclude MRI participation):
  16. An implant/device/condition that is contraindicated for MRI
  17. Weight above 158 kg
  18. Body habitus that would impede completion of MRI scan
  19. . Are undergoing FDG-PET and have any of the following conditions:
  20. Have received research-related radiation exposure that exceeds institutional guidelines (e.g., 50 mSv in the prior year), if applicable
  21. . 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.
  22. . Are undergoing a LP for CSF collection and taking any of the following types of anticoagulants: coumarins and indandiones, Factor Xa inhibitors, heparins, thrombin inhibitors.

Locations

  • University of California, San Diego accepting new patients
    La Jolla California 92037 United States
  • University of Colorado - Denver accepting new patients
    Aurora Colorado 80045 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Vaccinex Inc.
Links
Nonclinical research article: Anti-semaphorin 4D immunotherapy ameliorates neuropathology and some cognitive impairment in the YAC128 mouse model of Huntington disease.
ID
NCT02481674
Phase
Phase 2
Study Type
Interventional
Last Updated