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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 81
• 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
      • Neuricrine Clinical Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Neurocrine Clinical Site
    • Rogers, Arkansas, United States, 72758
      • Neurocrine Clinical Site
  • California
    • Anaheim, California, United States, 92805
      • Neurocrine Clinical Site
    • Fullerton, California, United States, 92835
      • Neurocrine Clinical Site
    • San Diego, California, United States, 92108
      • Neurocrine Clinical Site
    • Santa Ana, California, United States, 92705
      • Neurocrine Clinical Site
  • Colorado
    • Pueblo, Colorado, United States, 81003
      • Neurocrine Clinical Site
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Neurocrine Clinical Site
  • District of Columbia
    • Washington, District of Columbia, United States, 22207
      • Neurocrine Clinical Site
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Neurocrine Clinical Site
    • Hialeah, Florida, United States, 33012
      • Neurocrine Clinical Site
    • Miami, Florida, United States, 33136
      • Neurocrine Clinical Site
    • Miami, Florida, United States, 33125
      • Neurocrine Clinical Site
    • North Miami, Florida, United States, 33161
      • Neurocrine Clinical Site
    • Orlando, Florida, United States, 32803
      • Neurocrine Clinical Site
    • Palmetto Bay, Florida, United States, 33157
      • Neurocrine Clinical Site
    • Saint Petersburg, Florida, United States, 33701
      • Neurocrine Clinical Site
    • Spring Hill, Florida, United States, 34609
      • Neurocrine Clinical Site
    • Tallahassee, Florida, United States, 32308
      • Neurocrine Clinical Site
  • Georgia
    • Atlanta, Georgia, United States, 30338
      • Neurocrine Clinical Site
    • Fayetteville, Georgia, United States, 30214
      • Neurocrine Clinical Site
    • Savannah, Georgia, United States, 31406
      • Neurocrine Clinical Site
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Neurocrine Clinical Site
  • Indiana
    • South Bend, Indiana, United States, 46617
      • Neurocrine Clinical Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Neurocrine Clinical Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48015
      • Neurocrine Clinical Site
    • Bloomfield Hills, Michigan, United States, 48302
      • Neurocrine Clinical Site
    • West Bloomfield, Michigan, United States, 48322
      • 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
    • Cherry Hill, New Jersey, United States, 08002
      • Neurocrine Clinical Site
    • Mount Arlington, New Jersey, United States, 07856
      • Neurocrine Clinical Site
  • New York
    • New York, New York, United States, 10036
      • Neurocrine Clinical Site
    • S. Setauket, New York, United States, 11720
      • Neurocrine Clinical Site
  • North Carolina
    • Charlotte, North Carolina, United States, 29141
      • Neurocrine Clinical Site
  • Ohio
    • Mason, Ohio, United States, 45040
      • Neurocrine Clinical Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Neurocrine Clinical Site
  • Texas
    • Dallas, Texas, United States, 75243
      • Neurocrine Clinical Site
    • DeSoto, Texas, United States, 75115
      • Neurocrine Clinical Site
    • Houston, Texas, United States, 77030
      • Neurocrine Clinical Site
    • Houston, Texas, United States, 77058
      • Neurocrine Clinical Site
    • Irving, Texas, United States, 75062
      • Neurocrine Clinical Site
    • San Antonio, Texas, United States, 78249
      • Neurocrine Clinical Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Neurocrine Clinical Site
  • Washington
    • Bothell, Washington, United States, 98011
      • Neurocrine Clinical Site
    • Everett, Washington, United States, 98201
      • Neurocrine Clinical Site
    • Spokane, Washington, United States, 99202
      • 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
11. Have previously participated in an NBI-98854 clinical study, except for NBI-98854-1403 or NBI-98854-1501.
12. Have HIV, hepatitis B, or hepatitis C

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-randomization Valbenazine; 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; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: NBI-98854
Placebo Comparator: Randomized Placebo; 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; non-active dosage form
Experimental: Randomized Valbenazine; 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; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: NBI-98854

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2018
• Primary Completion (Actual): July 16, 2019
• Study Completion (Actual): July 16, 2019

Study Registration Dates

• First Submitted: May 8, 2018
• First Submitted That Met QC Criteria: May 8, 2018
• First Posted (Actual): May 21, 2018

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: April 26, 2022
• Last Verified: April 1, 2022

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-TS2005

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