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

This study is currently recruiting participants.
Verified October 2017 by Vaccinex Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02481674
First Posted: June 25, 2015
Last Update Posted: October 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Huntington Study Group
Information provided by (Responsible Party):
Vaccinex Inc.
  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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 24 or 42 months in Cohort B ]
    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 24 or 42 months in Cohort B ]
    Measurement of human anti human antibodies

  • Brain volumes measured by MRII [ Time Frame: Up to 12 months for cohort A and up to 18 or 36 months in Cohort B ]
  • Brain metabolic activity measured by FDG-PET Imaging [ Time Frame: Up to 12 months for cohort A and up to 18 or 36 months in Cohort B ]
  • Brain metabolic activity measured by TSPO-PET Imaging [ Time Frame: Up to 36 months in Cohort B ]
  • Clinical feature of HD: cognition (HD-CAB) [ Time Frame: Up to 15 months for cohort A and up to 24 or 42 months in Cohort B ]
    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 or 39 (UHDRS-Motor) or 24 or 42 months (Q-Motor) in Cohort B ]
    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 or 39 months in Cohort B ]
    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 or 39 months in Cohort B ]
    Measured by changes the UHDRS core functional assessments

  • Peak plasma concentration (Cmax) [ Time Frame: Up to 15 months for cohort A and up to 24 or 42 months in Cohort B ]
    PK parameter

  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 15 months for cohort A and up to 24 or 42 months in Cohort B ]
    PK parameter

  • Half-life of VX15/2503 [ Time Frame: Up to 15 months for cohort A and up to 24 or 42 months in Cohort B ]
    PK parameter

  • Cellular SEMA4D levels [ Time Frame: Up to 15 months for cohort A and up to 24 or 42 months in Cohort B ]
    PD parameter to determine the level of SEMA4D expression on T lymphocytes

  • Total sSEMA4D levels [ Time Frame: Up to 15 months for cohort A and up to 24 or 42 months in Cohort B ]
    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 or 39 months in Cohort B ]
    Exploratory plasma biomarker

  • Global Impression of Change [ Time Frame: Up to 18 or 36 months in Cohort B ]
    Assess overall response to therapy using patient and clinician reported impression of change


Estimated Enrollment: 240
Study Start Date: July 2015
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2020 (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 administered intravenously at a dose of 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). 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.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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).
  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. 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):

    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 and have any of the following conditions:

    a. Have received research-related radiation exposure that exceeds institutional guidelines (e.g., 50 mSv in the prior year), if applicable

  17. 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.
  18. 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02481674


Contacts
Contact: Huntington Study Group 1-800-487-7671 info@hsglimited.org
Contact: Clinical Trials Coordination Center 585-756-4800

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Victor Sung, MD, PhD         
United States, California
University of California, San Diego Recruiting
La Jolla, California, United States, 92037
Contact: Jody Corey-Bloom, MD, PhD         
United States, Colorado
University of Colorado - Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Lauren Seeberger, MD         
United States, District of Columbia
Georgetown University Recruiting
Washington, D.C., District of Columbia, United States, 20007
Contact: Karen Anderson, MD         
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30329
Contact: Stewart A Factor, DO         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: John Kamholz, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Kathrin LaFaver, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Diana Rosas, MD, MS         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Praveen Dayalu, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Brad Racette, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Karen Marder, MD, PhD         
University of Rochester Recruiting
Rochester, New York, United States, 14618
Contact: Richard Barbano, MD, PhD         
United States, North Carolina
Duke University Health Center Recruiting
Durham, North Carolina, United States, 27705
Contact: Burton Scott, MD, PhD         
Wake Forest University Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Francis Walker, MD         
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Andrew Duker, MD         
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Sandra Kostyk, MD, PhD         
University of Toledo Recruiting
Toledo, Ohio, United States, 43614
Contact: Lawrence Elmer, MD, PhD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Daniel Claassen, MD         
United States, Vermont
University of Vermont Recruiting
Burlington, Vermont, United States, 05401
Contact: James Boyd, MD         
Sponsors and Collaborators
Vaccinex Inc.
Huntington Study Group
Investigators
Principal Investigator: Andrew Feigin, MD The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders - NYU Langone Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Vaccinex Inc.
ClinicalTrials.gov Identifier: NCT02481674     History of Changes
Other Study ID Numbers: VX15/2503-N-131
First Submitted: June 19, 2015
First Posted: June 25, 2015
Last Update Posted: October 13, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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