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

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

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.

Study Overview

• Status: Completed
• Conditions: Tourette Syndrome
• Intervention / Treatment: Drug: Valbenazine; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00926
    • Neurocrine Clinical Site
• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
      • Neurocrine Clinical Site
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Neurocrine Clinical Site
  • California
    • Anaheim, California, United States, 92805
      • Neurocrine Clinical Site
    • San Diego, California, United States, 92108
      • Neurocrine Clinical Site
    • Santa Clarita, California, United States, 91321
      • Neurocrine Clinical Site
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Neurocrine Clinical Site
  • Florida
    • Hialeah, Florida, United States, 33012
      • Neurocrine Clinical Site
    • Hialeah, Florida, United States, 33013
      • Neurocrine Clinical Site
    • Hialeah, Florida, United States, 33018
      • Neurocrine Clinical Site
    • Loxahatchee Groves, Florida, United States, 33470
      • Neurocrine Clinical Site
    • Orange City, Florida, United States, 32763
      • Neurocrine Clinical Site
    • Orlando, Florida, United States, 32803
      • Neurocrine Clinical Site
    • Orlando, Florida, United States, 32801
      • Neurocrine Clinical Site
    • Tampa, Florida, United States, 33609
      • Neurocrine Clinical Site
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Neurocrine Clinical Site
    • Chicago, Illinois, United States, 60637
      • Neurocrine Clinical Site
    • Naperville, Illinois, United States, 60563
      • Neurocrine Clinical Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Neurocrine Clinical Site
  • Kansas
    • Leawood, Kansas, United States, 66206
      • Neurocrine Clinical Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Neurocrine Clinical Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Neurocrine Clinical Site
  • New Hampshire
    • Nashua, New Hampshire, United States, 03060
      • Neurocrine Clinical Site
  • New Jersey
    • Mount Arlington, New Jersey, United States, 07856
      • Neurocrine Clinical Site
    • Voorhees, New Jersey, United States, 08043
      • Neurocrine Clinical Site
  • New York
    • Bronx, New York, United States, 10467
      • Neurocrine Clinical Site
    • New York, New York, United States, 10036
      • Neurocrine Clinical Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Neurocrine Clinical Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Neurocrine Clinical Site
  • Texas
    • Dallas, Texas, United States, 75243
      • Neurocrine Clinical Site
    • Houston, Texas, United States, 77058
      • Neurocrine Clinical Site
    • Irving, Texas, United States, 75062
      • Neurocrine Clinical Site
  • Washington
    • Everett, Washington, United States, 98201
      • Neurocrine Clinical Site
    • Seattle, Washington, United States, 98105
      • Neurocrine Clinical Site
    • Spokane, Washington, United States, 99204
      • Neurocrine Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have a clinical diagnosis of Tourette Syndrome (TS)
2. Have at least moderate tic severity
3. Have TS symptoms that impair school, occupational, and/or social function
4. 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
5. Be in good general health
6. 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
7. 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:

1. Have an active, clinically significant unstable medical condition within 1 month prior to screening
2. Have a known history of long QT syndrome or cardiac arrhythmia
3. Have a known history of neuroleptic malignant syndrome
4. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed)
5. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors
6. Have a blood loss ≥250 mL or donated blood within 30 days prior to screening
7. Have a known history of substance dependence, substance (drug) or alcohol abuse
8. Have a significant risk of suicidal or violent behavior
9. Have initiated Comprehensive Behavioral Intervention for Tics (CBIT) during the screening period or at baseline or plan to initiate CBIT during the study
10. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2017
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 16, 2018

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Actual): June 28, 2021
• Last Update Submitted That Met QC Criteria: June 4, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: NBI-98854-TS2003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No