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Trial record 2 of 3 for:    vx15/2503

VX15/2503 Treatment for Huntington's Disease (SIGNAL)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Huntington Study Group
Information provided by (Responsible Party):
Vaccinex Inc.
ClinicalTrials.gov Identifier:
NCT02481674
First received: June 19, 2015
Last updated: September 2, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Huntington's Disease
Drug: VX15/2503
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Vaccinex Inc.:

Primary Outcome Measures:
  • Safety and tolerability as measured by drug related adverse event frequency and laboratory test abnormalities [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: Yes ]
    Safety laboratory tests will include serum biochemistry, hematology, coagulation, urinalysis, and immunophenotyping


Secondary Outcome Measures:
  • Immunogenicity of VX15/2503 as measured by the frequency and titer of anti-drug antibodies [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: Yes ]
    Measurement of human anti human antibodies

  • Brain volumes measured by MRI and FDG-PET Imaging [ Time Frame: Up to 12 months for cohort A and up to 18 months in Cohort B ] [ Designated as safety issue: No ]
  • Brain inflammation measured by TSPO-PET Imaging [ Time Frame: Up to 18 months in Cohort B ] [ Designated as safety issue: No ]
  • Clinical feature of HD: cognition (HD-CAB) [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    Measured by changes in the HD-CAB composite score

  • Clinical feature of HD: motor function (UHDRS-Motor, Q-Motor) [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    Measured by changes in the Qmotor and UHDRS motor scales

  • Clinical feature of HD: behavior [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    Measured by changes in the PBA questionnaire

  • Clinical feature of HD: functional abilities [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    Measured by changes the UHDRS core functional assessments

  • Peak plasma concentration (Cmax) [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    PK parameter

  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    PK parameter

  • Half-life of VX15/2503 [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    PK parameter

  • T-cell SEMA4D saturation [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    PD parameter to determine the binding of VX15/2503 to cellular SEMA4D

  • Total sSEMA4D levels [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    PD parameter to determine the levels of total soluble SEMA4D

  • Serum cytokine levels [ Time Frame: Up to 15 months for cohort A and up to 21 months in Cohort B ] [ Designated as safety issue: No ]
    Exploratory plasma biomarker


Enrollment: 89
Study Start Date: July 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VX15/2503
The study drug VX15/2503 will be administered via monthly intravenous infusions
Drug: VX15/2503
VX15/2503 is a humanized IgG4 monoclonal antibody and will be dosed intravenously at 20 mg/kg. The antibody is formulated at 20 mg/mL in 20 mM Sodium Acetate buffer, pH 5.4, containing 130 mM Sodium Chloride and 0.02% Polysorbate 80.
Placebo Comparator: Placebo
A placebo control will be administered via monthly intravenous infusions
Drug: Placebo
Placebo consists of formulation buffer only which is 20 mM Sodium Acetate buffer, pH 5.4, containing 130 mM Sodium Chloride and 0.02% Polysorbate 80.

Detailed Description:
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). Secondary objectives include determining the effect of VX15/2503 on brain volumes (MRI), FDG-PET imaging, 11C-PBR28 (TSPO) PET imaging (Cohort B only) 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 94 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 6 months with either drug or placebo (1:1) and then all subjects will be treated with drug for 6 months, followed by 3 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; 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 3 months of follow up. Treatment duration for each subject will be 18 months. 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; 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

Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria 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:

    1. Late prodromal HD as defined by a CAP score of greater than 200 and DCL 2 or 3,
    2. 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.
  3. Must fulfill both of the following criteria at Screening:

    1. Have undergone genetic testing with a known CAG repeat greater than or equal to 36,
    2. No features of juvenile HD (Westphal variant).
  4. 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.
  5. If male must agree to use a reliable method of birth control.
  6. Are willing and capable of providing informed consent for study participation, CAG genotyping (all subjects), and TSPO genotyping (Cohort B only, subset of subjects).
  7. Are capable of reading, writing, and communicating effectively with others.
  8. 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.
  9. Must meet all criteria required for the Randomization Authorization Flow (RAF) and be considered eligible by the RAF Reviewer.

Exclusion Criteria 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.
  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):

    1. An implant/device/condition that is contraindicated for MRI
    2. Weight above 158 kg
    3. Body habitus that would impede completion of MRI scan
  16. Are undergoing FDG-PET or TSPO-PET and have any of the following conditions:

    1. Have received research-related radiation exposure that exceeds institutional guidelines (e.g., 50 mSv in the prior year), if applicable
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02481674

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
University of California, San Diego
La Jolla, California, United States, 92037
United States, Colorado
University of Colorado - Denver
Aurora, Colorado, United States, 80045
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30329
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Massachusetts General Hospital
Charlestown, Massachusetts, United States, 02129
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48105
United States, Missouri
Washington University
St Louis, Missouri, United States, 63110
United States, New York
Columbia University
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14618
United States, North Carolina
Duke University Health Center
Durham, North Carolina, United States, 27705
Wake Forest University
Winston Salem, North Carolina, United States, 27157
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Ohio State University
Columbus, Ohio, United States, 43210
University of Toledo
Toledo, Ohio, United States, 43614
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Vaccinex Inc.
Huntington Study Group
Investigators
Principal Investigator: Andrew Feigin, MD Feinstein Institute for Medical Research North Shore-Long Island Jewish Health System
  More Information

Additional Information:
Publications:
Responsible Party: Vaccinex Inc.
ClinicalTrials.gov Identifier: NCT02481674     History of Changes
Other Study ID Numbers: VX15/2503-N-131 
Study First Received: June 19, 2015
Last Updated: September 2, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Vaccinex Inc.:
Prodromal Stage
Early Manifest Stage

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on December 02, 2016