Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome

Study Overview
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Brief Summary
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This is a Phase 2, double-blind, placebo-controlled, randomized withdrawal study to evaluate the safety and maintenance of efficacy of an optimized once-daily (qd) dose of NBI-98854 in pediatric subjects with TS.

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study to Evaluate 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: 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 Have previously participated in an NBI-98854 clinical study, except for NBI-98854-1403 or NBI-98854-1501. Have HIV, hepatitis B, or hepatitis C

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 |
| --- | --- |
| Experimental: Pre-randomization Valbenazine<br>Participants received valbenazine once daily for up to 12 weeks, depending on if and when randomization occured. 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 participants <50 kg and 80 mg for participants ≥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;|
| Placebo Comparator: Randomized Placebo<br>Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. | Drug: Placebo oral capsule<br>* non-active dosage form<br>|
| Experimental: Randomized Valbenazine<br>Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization. | 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 |
| --- | --- | --- |
| Time to Loss of Treatment Response | Loss of treatment response during the withdrawal period was defined as: 2 consecutive visits with 1) an increase in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) of greater than 35% or 7 points from the randomized withdrawal period baseline and 2) an increase in CGI-Tics-Severity score of ≥2 points from the randomized withdrawal period baseline; or discontinuation due to lack of efficacy or a treatment-emergent adverse event (TEAE) of worsening of tics. Median (lower and upper quartiles) Kaplan-Meier estimates for the time to loss of treatment response were not able to be calculated because of the low incidence of loss of treatment response events. | Randomization (Week 8, 10 or 12) through Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the YGTSS 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. Least-squares mean were estimated using a mixed-effects model for repeated measures. | Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization | 
| Change From Randomization Baseline to the Week 36 Visit in the YGTSS 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. | Randomization Baseline (Week 8, 10 or 12); Week 36 | 
| Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the 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. | Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization | 
| Change From Randomization Baseline to the Week 36 Visit in the 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. | Randomization Baseline (Week 8, 10 or 12); Week 36 |