Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease (KINECT-HD)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease

This is a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of valbenazine to treat chorea in participants with Huntington disease.

Study Overview

• Status: Completed
• Conditions: Chorea, Huntington
• Intervention / Treatment: Drug: Valbenazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Neurocrine Clinical Site
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Neurocrine Clinical Site
    • Toronto, Ontario, Canada, M2K 1E1
      • Neurocrine Clinical Site
    • Toronto, Ontario, Canada, M3B 2S7
      • Neurocrine Clinical Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Neurocrine Clinical Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Neurocrine Clinical Site
  • California
    • La Jolla, California, United States, 92037
      • Neurocrine Clinical Site
    • Sacramento, California, United States, 95817
      • Neurocrine Clinical Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Neurocrine Clinical Site
    • Englewood, Colorado, United States, 80113
      • Neurocrine Clinical Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Neurocrine Clinical Site
  • Florida
    • Gainesville, Florida, United States, 32608
      • Neurocrine Clinical Site
    • Miami, Florida, United States, 33136
      • Neurocrine Clinical Site
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Neurocrine Clinical Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Neurocrine Clinical Site
    • Chicago, Illinois, United States, 60612
      • Neurocrine Clinical Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Neurocrine Clinical Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Neurocrine Clinical Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Neurocrine Clinical Site
    • Wichita, Kansas, United States, 67226
      • Neurocrine Clinical Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Neurocrine Clinical Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Neurocrine Clinical Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Neurocrine Clinical Site
    • Boston, Massachusetts, United States, 02215
      • Neurocrine Clinical Site
    • Charlestown, Massachusetts, United States, 02129
      • Neurocrine Clinical Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Neurocrine Clinical Site
    • West Bloomfield, Michigan, United States, 48322
      • Neurocrine Clinical Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Neurocrine Clinical Site
  • New York
    • Rochester, New York, United States, 14618
      • Neurocrine Clinical Site
    • Williamsville, New York, United States, 14221
      • Neurocrine Clinical Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Neurocrine Clinical Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Neurocrine Clinical Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Neurocrine Clinical Site
    • Columbus, Ohio, United States, 43210
      • Neurocrine Clinical Site
    • Toledo, Ohio, United States, 43614
      • Neurocrine Clinical Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Neurocrine Clinical Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Neurocrine Clinical Site
    • Columbia, South Carolina, United States, 29203
      • Neurocrine Clinical Site
    • Greenville, South Carolina, United States, 29615
      • Neurocrine Clinical Site
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Neurocrine Clinical Site
  • Texas
    • Houston, Texas, United States, 77054
      • Neurocrine Clinical Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Neurocrine Clinical Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Neurocrine Clinical Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Neurocrine Clinical Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Neurocrine Clinical Site
    • Spokane, Washington, United States, 99202
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have a clinical diagnosis of Huntington Disease (HD) with chorea
2. Be able to walk, with or without the assistance of a person or device
3. Participants of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently while participating in the study until 30 days (females) or 90 days (males) after the last dose of the study drug
4. Be able to read and understand English

Exclusion Criteria:

1. Have a history of previously established therapy with a VMAT2 inhibitor, in the judgement of the investigator
2. Have difficulty swallowing
3. Are currently pregnant or breastfeeding
4. Have a known history of long QT syndrome, cardiac tachyarrhythmia, left bundle-branch block, atrioventricular block, uncontrolled bradyarrhythmia, or heart failure
5. Have an unstable or serious medical or psychiatric illness
6. Have a significant risk of suicidal behavior
7. Have a history of substance dependence or substance (drug) or alcohol abuse, within 1 year of screening
8. If taking antidepressant therapy, be on a stable regimen
9. Have received gene therapy at any time
10. Have received an investigational drug in a clinical study within 30 days of the baseline visit or plan to use such investigational drug (other than valbenazine) during the study
11. Have had a blood loss ≥550 milliliters (mL) or donated blood within 30 days before the baseline visit
12. Had a medically significant illness within 30 days before baseline, or any history of neuroleptic malignant syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valbenazine; Capsule, administered orally once daily for 12 weeks.	Drug: Valbenazine; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: NBI-98854
Placebo Comparator: Placebo; Capsule, administered orally once daily for 12 weeks.	Drug: Placebo; non-active dosage form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Screening Period Baseline to Maintenance Period in the Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) Score.	The TMC is part of the motor assessment of the UHDRS and measures chorea in 7 different body parts including the face, oral-buccal-lingual region, trunk and each limb independently. The TMC score is the sum of the individual scores and ranges from 0 to 28. A decrease in TMC scores indicates improvement in chorea symptoms.	Baseline (average of screening and Day -1), maintenance (average of Weeks 10 and 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Clinical Global Impression of Change (CGI-C) Responders at Week 12	The CGI-C is a 7-point scale that rates the overall global change in chorea symptoms since the initiation of study drug dosing, ranging from 1 (very much improved) to 7 (very much worse), as assessed by the investigator or qualified clinician designee. Participants whose CGI-C score was either a 1 (very much improved) or a 2 (much improved) were classified as responders.	Week 12
Percent of Patient Global Impression of Change (PGI-C) Responders at Week 12	The PGI-C is a 7-point scale that rates the overall global change in chorea symptoms since the initiation of study drug dosing, ranging from 1 (very much improved) to 7 (very much worse), as assessed by the participant. Participants whose PGI-C score was either a 1 (very much improved) or a 2 (much improved) were classified as responders.	Week 12
Change From Baseline to Week 12 in the Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function T-Score	The Neuro-QoL Upper Extremity Function Short Form consists of 8 questions about physical abilities, rated from 1 (unable to do) to 5 (without any difficulty). The Neuro-QoL scores were standardized as T-scores with a mean of 50 and standard deviation of 10. Scores below 50 indicated below average upper extremity function. The change from baseline to Week 12 in the Neuro-QoL Upper Extremity Function T-score are presented here. An increase in score indicates increased function.	Baseline, Week 12
Change From Baseline to Week 12 in the Neuro-QoL Lower Extremity Function T-Score	The Neuro-QoL Lower Extremity Function Short Form consists of 8 questions about physical abilities, rated from 1 (unable to do) to 5 (without any difficulty). The Neuro-QoL scores were standardized as T-scores with a mean of 50 and standard deviation of 10. Scores below 50 indicated below average upper extremity function. The change from baseline to Week 12 in the Neuro-QoL Upper Extremity Function T-score are presented here. An increase in score indicates better function.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Collaborators: Huntington Study Group
• Investigators: Study Director: Chief Medical Officer, Chief Medical Officer

Publications and helpful links

General Publications

• Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: April 2020. J Huntingtons Dis. 2020;9(2):185-197. doi: 10.3233/JHD-200002.
• Furr Stimming E, Claassen DO, Kayson E, Goldstein J, Mehanna R, Zhang H, Liang GS, Haubenberger D; Huntington Study Group KINECT-HD Collaborators. Safety and efficacy of valbenazine for the treatment of chorea associated with Huntington's disease (KINECT-HD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2023 Jun;22(6):494-504. doi: 10.1016/S1474-4422(23)00127-8. Erratum In: Lancet Neurol. 2023 Sep;22(9):e10. Lancet Neurol. 2023 Sep;22(9):e10.

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): October 15, 2021
• Study Completion (Actual): October 26, 2021

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: HD; Chorea; Movement disorder; Huntington; Huntington's; Tetrabenazine; Valbenazine; VMAT2-Inhibitor
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Huntington Disease; Chorea
• Other Study ID Numbers: NBI-98854-HD3005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No