Back to resultsSafety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome
Primary Purpose
Tourette Syndrome
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Valbenazine
Placebo oral capsule
Sponsored by
About this trial
This is an interventional treatment trial for Tourette Syndrome
Eligibility Criteria
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
Sites / Locations
- Neuricrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
- Neurocrine Clinical Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Pre-randomization Valbenazine
Randomized Placebo
Randomized Valbenazine
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03530293
Brief Title
Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Terminated
Why Stopped
Futility
Study Start Date
April 17, 2018 (Actual)
Primary Completion Date
July 16, 2019 (Actual)
Study Completion Date
July 16, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurocrine Biosciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tourette Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
open-label study drug treatment period followed by blinded randomization into treatment arm or placebo arm
Allocation
Randomized
Enrollment
81 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pre-randomization Valbenazine
Arm Type
Experimental
Arm Description
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.
Arm Title
Randomized Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Randomized Valbenazine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Valbenazine
Other Intervention Name(s)
NBI-98854
Intervention Description
vesicular monoamine transporter 2 (VMAT2) inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
non-active dosage form
Primary Outcome Measure Information:
Title
Time to Loss of Treatment Response
Description
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.
Time Frame
Randomization (Week 8, 10 or 12) through Week 36
Secondary Outcome Measure Information:
Title
Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the YGTSS TTS
Description
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.
Time Frame
Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization
Title
Change From Randomization Baseline to the Week 36 Visit in the YGTSS TTS
Description
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.
Time Frame
Randomization Baseline (Week 8, 10 or 12); Week 36
Title
Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the CGI-Tics-Severity Score
Description
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.
Time Frame
Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization
Title
Change From Randomization Baseline to the Week 36 Visit in the CGI-Tics-Severity Score
Description
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.
Time Frame
Randomization Baseline (Week 8, 10 or 12); Week 36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Development Lead
Organizational Affiliation
Neurocrine Biosciences
Official's Role
Study Director
Facility Information:
Facility Name
Neuricrine Clinical Site
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
Neurocrine Clinical Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Neurocrine Clinical Site
City
Rogers
State/Province
Arkansas
ZIP/Postal Code
72758
Country
United States
Facility Name
Neurocrine Clinical Site
City
Anaheim
State/Province
California
ZIP/Postal Code
92805
Country
United States
Facility Name
Neurocrine Clinical Site
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
Neurocrine Clinical Site
City
San Diego
State/Province
California
ZIP/Postal Code
92108
Country
United States
Facility Name
Neurocrine Clinical Site
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Neurocrine Clinical Site
City
Pueblo
State/Province
Colorado
ZIP/Postal Code
81003
Country
United States
Facility Name
Neurocrine Clinical Site
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06905
Country
United States
Facility Name
Neurocrine Clinical Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
22207
Country
United States
Facility Name
Neurocrine Clinical Site
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Neurocrine Clinical Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Neurocrine Clinical Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Neurocrine Clinical Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Neurocrine Clinical Site
City
North Miami
State/Province
Florida
ZIP/Postal Code
33161
Country
United States
Facility Name
Neurocrine Clinical Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Neurocrine Clinical Site
City
Palmetto Bay
State/Province
Florida
ZIP/Postal Code
33157
Country
United States
Facility Name
Neurocrine Clinical Site
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Neurocrine Clinical Site
City
Spring Hill
State/Province
Florida
ZIP/Postal Code
34609
Country
United States
Facility Name
Neurocrine Clinical Site
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
Neurocrine Clinical Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30338
Country
United States
Facility Name
Neurocrine Clinical Site
City
Fayetteville
State/Province
Georgia
ZIP/Postal Code
30214
Country
United States
Facility Name
Neurocrine Clinical Site
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31406
Country
United States
Facility Name
Neurocrine Clinical Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60634
Country
United States
Facility Name
Neurocrine Clinical Site
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46617
Country
United States
Facility Name
Neurocrine Clinical Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Neurocrine Clinical Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48015
Country
United States
Facility Name
Neurocrine Clinical Site
City
Bloomfield Hills
State/Province
Michigan
ZIP/Postal Code
48302
Country
United States
Facility Name
Neurocrine Clinical Site
City
West Bloomfield
State/Province
Michigan
ZIP/Postal Code
48322
Country
United States
Facility Name
Neurocrine Clinical Site
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68526
Country
United States
Facility Name
Neurocrine Clinical Site
City
Nashua
State/Province
New Hampshire
ZIP/Postal Code
03060
Country
United States
Facility Name
Neurocrine Clinical Site
City
Cherry Hill
State/Province
New Jersey
ZIP/Postal Code
08002
Country
United States
Facility Name
Neurocrine Clinical Site
City
Mount Arlington
State/Province
New Jersey
ZIP/Postal Code
07856
Country
United States
Facility Name
Neurocrine Clinical Site
City
New York
State/Province
New York
ZIP/Postal Code
10036
Country
United States
Facility Name
Neurocrine Clinical Site
City
S. Setauket
State/Province
New York
ZIP/Postal Code
11720
Country
United States
Facility Name
Neurocrine Clinical Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
29141
Country
United States
Facility Name
Neurocrine Clinical Site
City
Mason
State/Province
Ohio
ZIP/Postal Code
45040
Country
United States
Facility Name
Neurocrine Clinical Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Neurocrine Clinical Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75243
Country
United States
Facility Name
Neurocrine Clinical Site
City
DeSoto
State/Province
Texas
ZIP/Postal Code
75115
Country
United States
Facility Name
Neurocrine Clinical Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Neurocrine Clinical Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77058
Country
United States
Facility Name
Neurocrine Clinical Site
City
Irving
State/Province
Texas
ZIP/Postal Code
75062
Country
United States
Facility Name
Neurocrine Clinical Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78249
Country
United States
Facility Name
Neurocrine Clinical Site
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Neurocrine Clinical Site
City
Bothell
State/Province
Washington
ZIP/Postal Code
98011
Country
United States
Facility Name
Neurocrine Clinical Site
City
Everett
State/Province
Washington
ZIP/Postal Code
98201
Country
United States
Facility Name
Neurocrine Clinical Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
Neurocrine Clinical Site
City
San Juan
ZIP/Postal Code
00926
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome
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