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

Tracking Information

• First Submitted Date: September 23, 2019
• First Posted Date: September 25, 2019
• Results First Submitted Date: September 15, 2023
• Results First Posted Date: October 11, 2023
• Last Update Posted Date: October 11, 2023
• Actual Study Start Date: November 13, 2019
• Actual Primary Completion Date: October 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 15, 2023)

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.

Original Primary Outcome Measures (submitted: September 23, 2019)

Change from Baseline (average of Screening and Day -1) to Maintenance (average of Weeks 10 and 12) in the Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) Score. [ Time Frame: Screening, Day -1, Week 10, and Week 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 score indicates improvement in chorea.

Current Secondary Outcome Measures (submitted: September 15, 2023)

• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: September 23, 2019)

• Clinical Global Impression of Change (CGI-C) Response Status at Week 12 [ Time Frame: Week 12 ]
  The CGI-C is a 7-point Likert scale that rates the overall global improvement of chorea since the initiation of study drug dosing, ranging from 1 (very much improved) to 7 (very much worse), as assessed by the clinician. Subjects whose CGI-C score is either a 1 ("very much improved") or a 2 ("much improved") will be classified as responders.
• Patient Global Impression of Change (PGI-C) Response Status at Week 12 [ Time Frame: Week 12 ]
  The PGI-C is a 7-point Likert scale that rates the overall global improvement of chorea since the initiation of study drug dosing, ranging from 1 (very much improved) to 7 (very much worse), as assessed by the subject. Subjects whose PGI-C score is either a 1 ("very much improved") or a 2 ("much improved") will be classified as responders.
• Change from Baseline to Week 12 in the Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function [ Time Frame: Day -1 and 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).
• Change from Baseline to Week 12 in the Neuro-QoL Lower Extremity Function [ Time Frame: Day -1 and 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).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chorea, Huntington

Intervention

• Drug: Valbenazine
  vesicular monoamine transporter 2 (VMAT2) inhibitor
  Other Name: NBI-98854
• Drug: Placebo
  non-active dosage form

Study Arms

• Experimental: Valbenazine
  Capsule, administered orally once daily for 12 weeks.
  Intervention: Drug: Valbenazine
• Placebo Comparator: Placebo
  Capsule, administered orally once daily for 12 weeks.
  Intervention: Drug: Placebo

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 13, 2021): 128
• Original Estimated Enrollment (submitted: September 23, 2019): 120
• Actual Study Completion Date: October 26, 2021
• Actual Primary Completion Date: October 15, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04102579
• Other Study ID Numbers: NBI-98854-HD3005
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Neurocrine Biosciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Neurocrine Biosciences
• Original Study Sponsor: Same as current
• Collaborators: Huntington Study Group

Investigators

• Study Director: Chief Medical Officer; Chief Medical Officer

• PRS Account: Neurocrine Biosciences
• Verification Date: September 2023