Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome

Study Overview
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Brief Summary
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Phase 2, double-blind, placebo-controlled study to assess the safety and efficacy of NBI-98854 administered once daily (qd) for a total of 6 weeks of treatment. This study will enroll approximately 90 male and female pediatric subjects clinically diagnosed with Tourette Syndrome.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome

Conditions
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Tourette Syndrome

Intervention / Treatment
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* Drug: NBI-98854
* Drug: Placebo


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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Administered once daily for 6 weeks | Drug: Placebo<br> <br> |
| Experimental: Dose Group 1<br>Administered once daily for 6 weeks | Drug: NBI-98854<br> <br> |
| Experimental: Dose Group 2<br>Administered once daily for 6 weeks | Drug: NBI-98854<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 6 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 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression of Tourette Syndrome (CGI-TS) - Improvement Score at Week 6 | The CGI-TS-Improvement scale is used to assess overall improvement since the initiation of study drug dosing on a 7-point scale. Each of the CGI-TS-Improvement response categories was assigned a numerical score as follows: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = Not changed; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse. | Week 6 | 
| Participants Who Are a YGTSS TTS Responder at Week 6 | 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 6 | 
| Change From Baseline to Week 6 in the YGTSS Impairment Score | The YGTSS Impairment item is used to rate impairment due to tics using the following 50-point anchored scale: 0 = None; 10 = Minimal; 20 = Mild; 30 = Moderate; 40 = Marked; 50 = Severe. | Baseline, Week 6 | 
| Change From Baseline to Week 6 in the YGTSS Global Tic Severity Score | The YGTSS Global Tic Severity score is the sum of the YGTSS TTS and the YGTSS Impairment score and ranges from 0 to 100, with higher scores representing greater severity. | Baseline, Week 6 | 
| Change From Baseline to Week 6 in the Rush Video-based Tic Rating Scale (RTRS) Total Score | A modified RTRS was used in this study that includes short video recordings to measure 5 tic variables: number of body areas affected, frequency of motor and phonic tics, and severity of motor and phonic tics. The RTRS total score is calculated as the sum of the 5 domain scores, and ranges from 0 to 20, with higher scores representing greater severity. The final on-treatment visit was used in participants who discontinued prior to Week 6. | Baseline, Week 6 | 
| Change From Baseline to Week 6 in the Premonitory Urge for Tics Scale (PUTS) Total Score | The PUTS is an instrument for quantifying the premonitory urge phenomena associated with tics. It consists of 9 items, each of which is scored on a 4-point scale (1=not at all true, 2=a little true, 3=pretty much true, 4=very much true). The PUTS total score is calculated as the sum of the scores for the 9 items. The total score ranges from 9 to 36, with higher scores indicating a worse outcome. | Baseline, Week 6 | 
| Change From Baseline to Week 6 in the Clinical Global Impression of Tics (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 6 | 
| Participants Who Are a CGI-TS-Improvement Responder at Week 6 | A participant is classified as a CGI-TS-Improvement responder at a given visit if their CGI-TS-Improvement score is either a 1 (very much improved) or a 2 (much improved) at the visit. | Week 6 |