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

Study Overview
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Brief Summary
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This is a Phase 2b, randomized, double-blind, placebo-controlled, dose-optimization study to evaluate the efficacy, safety, and tolerability of NBI-98854 titrated to the subject's optimal dose administered once daily (qd) for a total of 12 weeks of treatment in pediatric subjects with TS.

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Dose Optimization Study to Assess the Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome

Conditions
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Tourette Syndrome

Intervention / Treatment
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* Drug: Valbenazine
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a clinical diagnosis of Tourette Syndrome (TS) Have at least moderate tic severity Have TS symptoms that impair school, occupational, and/or social function If using maintenance medication(s) for TS or TS spectrum diagnoses (e.g. obsessive-compulsive disorder [OCD], Attention-Deficit Hyperactivity Disorder [ADHD]), be on stable doses Be in good general health Adolescent subjects (12 to 17 years of age) must have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids and a negative alcohol screen Subjects of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study Exclusion Criteria: Have an active, clinically significant unstable medical condition within 1 month prior to screening Have a known history of long QT syndrome or cardiac arrhythmia Have a known history of neuroleptic malignant syndrome Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed) Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors Have a blood loss ≥250 mL or donated blood within 30 days prior to screening Have a known history of substance dependence, substance (drug) or alcohol abuse Have a significant risk of suicidal or violent behavior Have initiated Comprehensive Behavioral Intervention for Tics (CBIT) during the screening period or at baseline or plan to initiate CBIT during the study Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo (matching valbenazine) once daily for 12 weeks. | Drug: Placebo oral capsule<br>* non-active dosage form<br>|
| Experimental: Valbenazine<br>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. | Drug: Valbenazine<br>* vesicular monoamine transporter 2 (VMAT2) inhibitor<br>* Other names: NBI-98854;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) | 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. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in the Clinical Global Impression of Tics Severity (CGI-Tics-Severity) Score | 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. | Baseline, Week 12 | 
| Participants Who Are a Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) Responder at 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. | Baseline, Week 12 | 
| Participants Who Are a Clinical Global Impression of Tourette Syndrome Improvement (CGI-TS-Improvement) Responder at 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. | Week 12 |