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

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ClinicalTrials.gov Identifier: NCT02481674
Recruitment Status : Recruiting
First Posted : June 25, 2015
Last Update Posted : April 30, 2018
Sponsor:
Collaborator:
Huntington Study Group
Information provided by (Responsible Party):
Vaccinex Inc.

Brief 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.

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

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
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
Study Start Date : July 2015
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. Brain volumes measured by MRII [ Time Frame: Up to 12 months for cohort A and up to 18 or 36 months in Cohort B ]
  3. 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 ]
  4. Brain metabolic activity measured by TSPO-PET Imaging [ Time Frame: Up to 36 months in Cohort B ]
  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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



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, Older Adult)
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.

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

  Show 24 Study Locations
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

Additional Information:
Publications:
Responsible Party: Vaccinex Inc.
ClinicalTrials.gov Identifier: NCT02481674     History of Changes
Other Study ID Numbers: VX15/2503-N-131
First Posted: June 25, 2015    Key Record Dates
Last Update Posted: April 30, 2018
Last Verified: April 2018

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