Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease (NCT NCT04102579)

Last Updated: 2023-10-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

128 participants

Primary outcome timeframe

Baseline (average of screening and Day -1), maintenance (average of Weeks 10 and 12)

Results posted on

2023-10-11

Participant Flow

Participant milestones

Participant milestones
Measure	Valbenazine Capsule, administered orally once daily for 12 weeks.	Placebo Capsule, administered orally once daily for 12 weeks.
Overall Study STARTED	64	64
Overall Study Received at Least 1 Dose of Study Drug	64	63
Overall Study COMPLETED	57	54
Overall Study NOT COMPLETED	7	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Valbenazine Capsule, administered orally once daily for 12 weeks.	Placebo Capsule, administered orally once daily for 12 weeks.
Overall Study Withdrawal by Subject	3	4
Overall Study Lost to Follow-up	0	1
Overall Study Discontinued Due to COVID-19-related Study Pause	3	4
Overall Study Other than Specified	1	0
Overall Study Not Dosed with Study Drug	0	1

Baseline Characteristics

Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Valbenazine n=64 Participants Capsule, administered orally once daily for 12 weeks.	Placebo n=63 Participants Capsule, administered orally once daily for 12 weeks.	Total n=127 Participants Total of all reporting groups
Age, Continuous	54.1 years STANDARD_DEVIATION 10.1 • n=5 Participants	53.6 years STANDARD_DEVIATION 11.6 • n=7 Participants	53.8 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	36 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	27 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	60 Participants n=7 Participants	119 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	62 Participants n=7 Participants	122 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	62 participants n=5 Participants	56 participants n=7 Participants	118 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (average of screening and Day -1), maintenance (average of Weeks 10 and 12)

Population: 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.

Outcome measures

Outcome measures
Measure	Valbenazine n=64 Participants Capsule, administered orally once daily for 12 weeks.	Placebo n=61 Participants Capsule, administered orally once daily for 12 weeks.
Change From Screening Period Baseline to Maintenance Period in the Unified Huntington's Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) Score.	-4.60 units on a scale Standard Error 0.43	-1.44 units on a scale Standard Error 0.44

SECONDARY outcome

Timeframe: Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Valbenazine n=56 Participants Capsule, administered orally once daily for 12 weeks.	Placebo n=53 Participants Capsule, administered orally once daily for 12 weeks.
Percent of Clinical Global Impression of Change (CGI-C) Responders at Week 12	42.9 percentage of responders	13.2 percentage of responders

SECONDARY outcome

Timeframe: Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Valbenazine n=55 Participants Capsule, administered orally once daily for 12 weeks.	Placebo n=53 Participants Capsule, administered orally once daily for 12 weeks.
Percent of Patient Global Impression of Change (PGI-C) Responders at Week 12	52.7 percentage of responders	26.4 percentage of responders

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Valbenazine n=64 Participants Capsule, administered orally once daily for 12 weeks.	Placebo n=61 Participants Capsule, administered orally once daily for 12 weeks.
Change From Baseline to Week 12 in the Quality of Life in Neurological Disorders (Neuro-QoL) Upper Extremity Function T-Score	-1.58 units on a scale Standard Error 1.01	-3.00 units on a scale Standard Error 1.04

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Valbenazine n=64 Participants Capsule, administered orally once daily for 12 weeks.	Placebo n=61 Participants Capsule, administered orally once daily for 12 weeks.
Change From Baseline to Week 12 in the Neuro-QoL Lower Extremity Function T-Score	-0.27 units on a scale Standard Error 0.82	0.61 units on a scale Standard Error 0.84

Adverse Events

Valbenazine

Serious events: 1 serious events

Other events: 35 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 17 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Valbenazine n=64 participants at risk Capsule, administered orally once daily for 12 weeks.	Placebo n=63 participants at risk Capsule, administered orally once daily for 12 weeks.
Psychiatric disorders Psychotic disorder	0.00% 0/64 • Day 1 (after dosing) through Week 14 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.	1.6% 1/63 • Day 1 (after dosing) through Week 14 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.
Cardiac disorders Colon cancer	0.00% 0/64 • Day 1 (after dosing) through Week 14 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.	1.6% 1/63 • Day 1 (after dosing) through Week 14 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.
Skin and subcutaneous tissue disorders Angioedema	1.6% 1/64 • Day 1 (after dosing) through Week 14 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.	0.00% 0/63 • Day 1 (after dosing) through Week 14 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.

Other adverse events

Other adverse events
Measure	Valbenazine n=64 participants at risk Capsule, administered orally once daily for 12 weeks.	Placebo n=63 participants at risk Capsule, administered orally once daily for 12 weeks.
Skin and subcutaneous tissue disorders Rash	7.8% 5/64 • Day 1 (after dosing) through Week 14 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.	0.00% 0/63 • Day 1 (after dosing) through Week 14 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.
Skin and subcutaneous tissue disorders Urticaria	7.8% 5/64 • Day 1 (after dosing) through Week 14 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.	0.00% 0/63 • Day 1 (after dosing) through Week 14 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.
General disorders Fatigue	14.1% 9/64 • Day 1 (after dosing) through Week 14 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.	9.5% 6/63 • Day 1 (after dosing) through Week 14 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.
Injury, poisoning and procedural complications Fall	12.5% 8/64 • Day 1 (after dosing) through Week 14 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.	12.7% 8/63 • Day 1 (after dosing) through Week 14 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.
Nervous system disorders Somnolence	15.6% 10/64 • Day 1 (after dosing) through Week 14 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.	3.2% 2/63 • Day 1 (after dosing) through Week 14 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.
Nervous system disorders Akathisia	6.2% 4/64 • Day 1 (after dosing) through Week 14 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.	4.8% 3/63 • Day 1 (after dosing) through Week 14 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.

Additional Information

Neurocrine Medical Information Call Center

Neurocrine Biosciences

Phone: 877-641-3461

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER