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

• ClinicalTrials.gov Identifier: NCT04102579
• Recruitment Status: Completed
• First Posted: September 25, 2019
• Results First Posted: October 11, 2023
• Last Update Posted: October 11, 2023
• Sponsor: Neurocrine Biosciences
• Collaborator: Huntington Study Group
• Information provided by (Responsible Party): Neurocrine Biosciences

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chorea, Huntington	Drug: Valbenazine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 13, 2019
• Actual Primary Completion Date: October 15, 2021
• Actual Study Completion Date: October 26, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Screening Period Baseline to Maintenance Period in the Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) Score. [ Time Frame: Baseline (average of screening and Day -1), maintenance (average of Weeks 10 and 12) ]
   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.

Secondary Outcome Measures :

1. Percent of Clinical Global Impression of Change (CGI-C) Responders at Week 12 [ Time Frame: 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.

2. Percent of Patient Global Impression of Change (PGI-C) Responders at Week 12 [ Time Frame: 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.

3. Change From Baseline to Week 12 in the Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function T-Score [ Time Frame: Baseline, Week 12 ]
   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.
4. Change From Baseline to Week 12 in the Neuro-QoL Lower Extremity Function T-Score [ Time Frame: Baseline, Week 12 ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Neurocrine Clinical Site

Birmingham, Alabama, United States, 35233

United States, Arkansas

Neurocrine Clinical Site

Little Rock, Arkansas, United States, 72205

United States, California

Neurocrine Clinical Site

La Jolla, California, United States, 92037

Neurocrine Clinical Site

Sacramento, California, United States, 95817

United States, Colorado

Neurocrine Clinical Site

Aurora, Colorado, United States, 80045

Neurocrine Clinical Site

Englewood, Colorado, United States, 80113

United States, District of Columbia

Neurocrine Clinical Site

Washington, District of Columbia, United States, 20007

United States, Florida

Neurocrine Clinical Site

Gainesville, Florida, United States, 32608

Neurocrine Clinical Site

Miami, Florida, United States, 33136

United States, Georgia

Neurocrine Clinical Site

Atlanta, Georgia, United States, 30329

United States, Illinois

Neurocrine Clinical Site

Chicago, Illinois, United States, 60611

Neurocrine Clinical Site

Chicago, Illinois, United States, 60612

United States, Indiana

Neurocrine Clinical Site

Indianapolis, Indiana, United States, 46202

United States, Iowa

Neurocrine Clinical Site

Iowa City, Iowa, United States, 52242

United States, Kansas

Neurocrine Clinical Site

Kansas City, Kansas, United States, 66160

Neurocrine Clinical Site

Wichita, Kansas, United States, 67226

United States, Kentucky

Neurocrine Clinical Site

Louisville, Kentucky, United States, 40202

United States, Louisiana

Neurocrine Clinical Site

New Orleans, Louisiana, United States, 70121

United States, Massachusetts

Neurocrine Clinical Site

Boston, Massachusetts, United States, 02118

Neurocrine Clinical Site

Boston, Massachusetts, United States, 02215

Neurocrine Clinical Site

Charlestown, Massachusetts, United States, 02129

United States, Michigan

Neurocrine Clinical Site

Ann Arbor, Michigan, United States, 48109

Neurocrine Clinical Site

West Bloomfield, Michigan, United States, 48322

United States, Nebraska

Neurocrine Clinical Site

Omaha, Nebraska, United States, 68198

United States, New York

Neurocrine Clinical Site

Rochester, New York, United States, 14618

Neurocrine Clinical Site

Williamsville, New York, United States, 14221

United States, North Carolina

Neurocrine Clinical Site

Durham, North Carolina, United States, 27705

United States, North Dakota

Neurocrine Clinical Site

Fargo, North Dakota, United States, 58103

United States, Ohio

Neurocrine Clinical Site

Cleveland, Ohio, United States, 44195

Neurocrine Clinical Site

Columbus, Ohio, United States, 43210

Neurocrine Clinical Site

Toledo, Ohio, United States, 43614

United States, Pennsylvania

Neurocrine Clinical Site

Pittsburgh, Pennsylvania, United States, 15213

United States, South Carolina

Neurocrine Clinical Site

Charleston, South Carolina, United States, 29425

Neurocrine Clinical Site

Columbia, South Carolina, United States, 29203

Neurocrine Clinical Site

Greenville, South Carolina, United States, 29615

United States, Tennessee

Neurocrine Clinical Site

Nashville, Tennessee, United States, 37212

United States, Texas

Neurocrine Clinical Site

Houston, Texas, United States, 77054

United States, Utah

Neurocrine Clinical Site

Salt Lake City, Utah, United States, 84108

United States, Vermont

Neurocrine Clinical Site

Burlington, Vermont, United States, 05401

United States, Virginia

Neurocrine Clinical Site

Charlottesville, Virginia, United States, 22908

United States, Washington

Neurocrine Clinical Site

Seattle, Washington, United States, 98195

Neurocrine Clinical Site

Spokane, Washington, United States, 99202

Canada, British Columbia

Neurocrine Clinical Site

Vancouver, British Columbia, Canada, V6T 2B5

Canada, Ontario

Neurocrine Clinical Site

Ottawa, Ontario, Canada, K1Y 4E9

Neurocrine Clinical Site

Toronto, Ontario, Canada, M2K 1E1

Neurocrine Clinical Site

Toronto, Ontario, Canada, M3B 2S7

Sponsors and Collaborators

Neurocrine Biosciences

Huntington Study Group

Investigators

• Study Director: Chief Medical Officer; Chief Medical Officer

  Study Documents (Full-Text)

Documents provided by Neurocrine Biosciences:

Study Protocol  [PDF] April 12, 2021

Statistical Analysis Plan  [PDF] November 19, 2021

More Information

Additional Information:

Study website 

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Neurocrine Biosciences
• ClinicalTrials.gov Identifier: NCT04102579
• Other Study ID Numbers: NBI-98854-HD3005
• First Posted: September 25, 2019
• Results First Posted: October 11, 2023
• Last Update Posted: October 11, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Neurocrine Biosciences:

Huntington's; Huntington; Chorea; Movement disorder; Valbenazine; HD; Tetrabenazine; VMAT2-Inhibitor

Additional relevant MeSH terms:

Huntington Disease; Chorea; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurologic Manifestations