Trial Outcomes & Findings for Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome (NCT NCT03325010)

Last Updated: 2021-06-28

Results Overview

The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

127 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2021-06-28

Participant Flow

This study enrolled male and female pediatric participants, 6 to 17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4th or 5th Editions (DSM-IV or -V) diagnosis of Tourette Syndrome (TS) in the United States. The first and last participants were enrolled on 05 October 2017 and 19 July 2018, respectively.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Overall Study STARTED	64	63
Overall Study Safety Analysis Set	62	59
Overall Study Full Analysis Set	61	58
Overall Study COMPLETED	55	43
Overall Study NOT COMPLETED	9	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Overall Study Adverse Event	3	8
Overall Study Protocol Violation	1	8
Overall Study Withdrawal by Subject	1	3
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	1	1
Overall Study Lack of Efficacy	2	0

Baseline Characteristics

Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=61 Participants Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine n=58 Participants Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.	Total n=119 Participants Total of all reporting groups
Age, Continuous	12.4 Years STANDARD_DEVIATION 2.6 • n=5 Participants	12.2 Years STANDARD_DEVIATION 2.7 • n=7 Participants	12.3 Years STANDARD_DEVIATION 2.6 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	48 Participants n=7 Participants	100 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=5 Participants	44 Participants n=7 Participants	90 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/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	49 Participants n=5 Participants	53 Participants n=7 Participants	102 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Multiple	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)	31.2 score on scale STANDARD_DEVIATION 9.0 • n=5 Participants	29.3 score on scale STANDARD_DEVIATION 8.7 • n=7 Participants	30.3 score on scale STANDARD_DEVIATION 8.9 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Full analysis set, which includes all randomized participants who have at least one evaluable change from baseline value for TTS reported at a visit (either scheduled or mapped early termination visit) during the treatment period. Dose levels based on weight group and each individual participant's optimized dosing titration were prespecified to be combined within each arm.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine n=58 Participants Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Change From Baseline to Week 12 in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)	-6.8 score on a scale Standard Error 1.0	-8.9 score on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: Baseline, Week 12

The CGI-Tics-Severity scale is used to assess overall severity on a 7-point scale. Each of the CGI-Tics-Severity response categories was assigned a numerical score as follows: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patient.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine n=58 Participants Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Change From Baseline to Week 12 in the Clinical Global Impression of Tics Severity (CGI-Tics-Severity) Score	-0.7 Score on scale Standard Error 0.1	-1.0 Score on scale Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline, Week 12

A TTS responder is defined, on a per-visit basis, as a participant whose TTS value is reduced by at least 30% from baseline at the specified postbaseline visit.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine n=43 Participants Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Participants Who Are a Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) Responder at Week 12	21 Participants	18 Participants

SECONDARY outcome

Timeframe: Week 12

The CGI-TS-Improvement scale is used to assess overall improvement since the initiation of study drug dosing on a 7-point scale. A CGI-TS-Improvement responder is defined, on a per-visit basis, as a participant whose CGI-TS-Improvement score is 1 ("Very much improved") or 2 ("Much improved") at the specified postbaseline visit.

Outcome measures

Outcome measures
Measure	Placebo n=54 Participants Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine n=43 Participants Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Participants Who Are a Clinical Global Impression of Tourette Syndrome Improvement (CGI-TS-Improvement) Responder at Week 12	12 Participants	24 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Valbenazine

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=62 participants at risk Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine n=59 participants at risk Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Skin and subcutaneous tissue disorders Rash	1.6% 1/62 • Up to 14 Weeks	0.00% 0/59 • Up to 14 Weeks

Other adverse events

Other adverse events
Measure	Placebo n=62 participants at risk Participants received placebo (matching valbenazine) once daily for 12 weeks.	Valbenazine n=59 participants at risk Participants received valbenazine once daily for 12 weeks. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for subjects \<50 kg and 80 mg for subjects ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Gastrointestinal disorders Abdominal pain upper	3.2% 2/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Gastrointestinal disorders Nausea	3.2% 2/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Gastrointestinal disorders Vomiting	6.5% 4/62 • Up to 14 Weeks	10.2% 6/59 • Up to 14 Weeks
General disorders Fatigue	8.1% 5/62 • Up to 14 Weeks	10.2% 6/59 • Up to 14 Weeks
General disorders Irritability	3.2% 2/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Infections and infestations Influenza	1.6% 1/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Nervous system disorders Headache	8.1% 5/62 • Up to 14 Weeks	18.6% 11/59 • Up to 14 Weeks
Nervous system disorders Somnolence	0.00% 0/62 • Up to 14 Weeks	18.6% 11/59 • Up to 14 Weeks
Psychiatric disorders Anxiety	3.2% 2/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Psychiatric disorders Restlessness	0.00% 0/62 • Up to 14 Weeks	5.1% 3/59 • Up to 14 Weeks
Psychiatric disorders Suicidal ideation	1.6% 1/62 • Up to 14 Weeks	8.5% 5/59 • Up to 14 Weeks

Additional Information

Neurocrine Medical Information

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