This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
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:
Collaborator:
Huntington Study Group
Information provided by (Responsible Party):
Neurocrine Biosciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chorea, Huntington
Interventions Drug: Valbenazine
Drug: Placebo
Enrollment 128
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Valbenazine Placebo
Hide Arm/Group Description Capsule, administered orally once daily for 12 weeks. Capsule, administered orally once daily for 12 weeks.
Period Title: Overall Study
Started 64 64
Received at Least 1 Dose of Study Drug 64 63
Completed 57 54
Not Completed 7 10
Reason Not Completed
Withdrawal by Subject             3             4
Lost to Follow-up             0             1
Discontinued Due to COVID-19-related Study Pause             3             4
Other than Specified             1             0
Not Dosed with Study Drug             0             1
Arm/Group Title Valbenazine Placebo Total
Hide Arm/Group Description Capsule, administered orally once daily for 12 weeks. Capsule, administered orally once daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 64 63 127
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 64 participants 63 participants 127 participants
54.1  (10.1) 53.6  (11.6) 53.8  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 63 participants 127 participants
Female
33
  51.6%
36
  57.1%
69
  54.3%
Male
31
  48.4%
27
  42.9%
58
  45.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 63 participants 127 participants
Hispanic or Latino
5
   7.8%
3
   4.8%
8
   6.3%
Not Hispanic or Latino
59
  92.2%
60
  95.2%
119
  93.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 63 participants 127 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.6%
0
   0.0%
1
   0.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.6%
0
   0.0%
1
   0.8%
White
60
  93.8%
62
  98.4%
122
  96.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   3.1%
1
   1.6%
3
   2.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 64 participants 63 participants 127 participants
Canada 2 7 9
United States 62 56 118
1.Primary Outcome
Title Change From Screening Period Baseline to Maintenance Period in the Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) Score.
Hide Description 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.
Time Frame Baseline (average of screening and Day -1), maintenance (average of Weeks 10 and 12)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who are randomly assigned to a treatment group and who had at least 1 evaluable TMC change from baseline score during the 12-week double-blind treatment period.
Arm/Group Title Valbenazine Placebo
Hide Arm/Group Description:
Capsule, administered orally once daily for 12 weeks.
Capsule, administered orally once daily for 12 weeks.
Overall Number of Participants Analyzed 64 61
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.60  (0.43) -1.44  (0.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valbenazine, Placebo
Comments Results were analyzed using a mixed-effect model repeated measures (MMRM) analysis. The model included the screening period baseline TMC as a covariate, and treatment group, visit, treatment group-by-visit interaction, and baseline-by-visit interaction as fixed effects. Participant was included as a random effect.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance achieved if p-value <0.05.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Means Difference
Estimated Value -3.16
Confidence Interval (2-Sided) 95%
-4.37 to -1.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments LS Means Difference = Valbenazine - Placebo
2.Secondary Outcome
Title Percent of Clinical Global Impression of Change (CGI-C) Responders at Week 12
Hide Description

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.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomly assigned to a treatment group, and who had at least 1 evaluable TMC change from baseline score and observed data at Week 12.
Arm/Group Title Valbenazine Placebo
Hide Arm/Group Description:
Capsule, administered orally once daily for 12 weeks.
Capsule, administered orally once daily for 12 weeks.
Overall Number of Participants Analyzed 56 53
Measure Type: Number
Unit of Measure: percentage of responders
42.9 13.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valbenazine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments Statistical significance achieved if p-value <0.05.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Difference in Responders
Estimated Value 29.65
Confidence Interval (2-Sided) 95%
10.77 to 45.37
Estimation Comments Percent Difference in Responders (%) = Valbenazine - Placebo
3.Secondary Outcome
Title Percent of Patient Global Impression of Change (PGI-C) Responders at Week 12
Hide Description

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.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomly assigned to a treatment group, and who had at least 1 evaluable TMC change from baseline score and observed data at Week 12.
Arm/Group Title Valbenazine Placebo
Hide Arm/Group Description:
Capsule, administered orally once daily for 12 weeks.
Capsule, administered orally once daily for 12 weeks.
Overall Number of Participants Analyzed 55 53
Measure Type: Number
Unit of Measure: percentage of responders
52.7 26.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valbenazine, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments Statistical significance achieved if p-value <0.05.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Difference in Responders
Estimated Value 26.31
Confidence Interval (2-Sided) 95%
6.32 to 43.74
Estimation Comments Percent Difference in Responders (%) = Valbenazine - Placebo
4.Secondary Outcome
Title Change From Baseline to Week 12 in the Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function T-Score
Hide Description 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who are randomly assigned to a treatment group and who had at least 1 evaluable TMC change from baseline score during the 12-week double-blind treatment period.
Arm/Group Title Valbenazine Placebo
Hide Arm/Group Description:
Capsule, administered orally once daily for 12 weeks.
Capsule, administered orally once daily for 12 weeks.
Overall Number of Participants Analyzed 64 61
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.58  (1.01) -3.00  (1.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valbenazine, Placebo
Comments LS mean was based on the MMRM model which included corresponding baseline value of the Neuro-QoL Upper Extremity Function T-score as a covariate; treatment group, visit, baseline-by-visit interaction, and treatment group-by-visit interaction as fixed effects; and participant as a random effect.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3304
Comments Statistical significance achieved if p-value <0.05.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
-1.46 to 4.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.46
Estimation Comments LS Means Difference = Valbenazine - Placebo
5.Secondary Outcome
Title Change From Baseline to Week 12 in the Neuro-QoL Lower Extremity Function T-Score
Hide Description 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.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who are randomly assigned to a treatment group and who had at least 1 evaluable TMC change from baseline score during the 12-week double-blind treatment period.
Arm/Group Title Valbenazine Placebo
Hide Arm/Group Description:
Capsule, administered orally once daily for 12 weeks.
Capsule, administered orally once daily for 12 weeks.
Overall Number of Participants Analyzed 64 61
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.27  (0.82) 0.61  (0.84)
Time Frame Day 1 (after dosing) through Week 14
Adverse Event Reporting Description All-cause mortality, serious adverse events, and other adverse events were assessed using the safety analysis population which included all participants who were randomly assigned to a treatment group, received at least 1 dose of study treatment, and had any postbaseline safety data. Treatment-emergent adverse events were those that occurred on or after first dose date of study treatment and up to 14 days after the last dose of study treatment.
 
Arm/Group Title Valbenazine Placebo
Hide Arm/Group Description Capsule, administered orally once daily for 12 weeks. Capsule, administered orally once daily for 12 weeks.
All-Cause Mortality
Valbenazine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/64 (0.00%)   1/63 (1.59%) 
Hide Serious Adverse Events
Valbenazine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/64 (1.56%)   2/63 (3.17%) 
Cardiac disorders     
Colon cancer  1 [1]  0/64 (0.00%)  1/63 (1.59%) 
Psychiatric disorders     
Psychotic disorder  1  0/64 (0.00%)  1/63 (1.59%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  1/64 (1.56%)  0/63 (0.00%) 
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
[1]
A serious adverse event of colon cancer in the placebo group resulted in death.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Valbenazine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   35/64 (54.69%)   17/63 (26.98%) 
General disorders     
Fatigue  1  9/64 (14.06%)  6/63 (9.52%) 
Injury, poisoning and procedural complications     
Fall  1  8/64 (12.50%)  8/63 (12.70%) 
Nervous system disorders     
Somnolence  1  10/64 (15.63%)  2/63 (3.17%) 
Akathisia  1  4/64 (6.25%)  3/63 (4.76%) 
Skin and subcutaneous tissue disorders     
Rash  1  5/64 (7.81%)  0/63 (0.00%) 
Urticaria  1 [1]  5/64 (7.81%)  0/63 (0.00%) 
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
[1]
Note: One additional participant in the valbenazine group had an event of urticaria that was coded under the system organ class of immune system disorders.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Generally, the PI has the right to publish results provided such publication does not violate confidentiality or IP provisions within the contract with the Sponsor. Prior to submission for publication or presentation of results, the PI must provide the Sponsor time for review. The Sponsor can request the PI to withhold or remove information from all publications. For a multi-center study, any publication of results by the PI shall not be made before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Neurocrine Medical Information Call Center
Organization: Neurocrine Biosciences
Phone: 877-641-3461
EMail: medinfo@neurocrine.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Neurocrine Biosciences
ClinicalTrials.gov Identifier: NCT04102579    
Other Study ID Numbers: NBI-98854-HD3005
First Submitted: September 23, 2019
First Posted: September 25, 2019
Results First Submitted: September 15, 2023
Results First Posted: October 11, 2023
Last Update Posted: October 11, 2023