Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome

• Sponsor: Neurocrine Biosciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03444038
• Collaborator: (none)
• Enrollment: 85
• Locations: 37
• Arm: 1
• Actual Duration (Months): 17.1
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 2b, multicenter, open-label study to evaluate the safety and tolerability of optimized doses of NBI-98854 administered once daily for 24 weeks in pediatric subjects with Tourette Syndrome.

Condition or Disease	Intervention/Treatment	Phase
Tourette Syndrome	Drug: Valbenazine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Safety and Tolerability Study of Optimized Doses of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
• Actual Study Start Date: Feb 8, 2018
• Actual Primary Completion Date: Jul 12, 2019
• Actual Study Completion Date: Jul 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valbenazine Valbenazine administered once daily for up to 24 weeks	Drug: Valbenazine; vesicular monoamine transporter 2 (VMAT2) inhibitor; Other Names: NBI-98854

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Baseline through Week 24]

   A TEAE is an adverse event not present prior to the initiation of study drug dosing, or is an already present event that worsens either in intensity or frequency following the initiation of study drug dosing. All qualifying TEAE are reported regardless of threshold.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Have participated in and completed Study NBI-98854-TS2003

2. Have a clinical diagnosis of Tourette Syndrome (TS)

3. 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

4. Be in good general health

5. Adolescent subjects (12 to 18 years of age) must have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids and a negative alcohol screen

6. 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 vesicular monoamine transporter 2 (VMAT2) inhibitors

6. Have a blood loss ≥250 mL or donated blood within 56 days prior to baseline

7. Have a known history of substance (drug) dependence, or substance or alcohol abuse

8. Have a significant risk of suicidal or violent behavior

9. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurocrine Clinical Site	Sun City	Arizona	United States	85351
2	Neurocrine Clinical Site	Anaheim	California	United States	92805
3	Neurocrine Clinical Site	San Diego	California	United States	92108
4	Neurocrine Clinical Site	Santa Ana	California	United States	92705
5	Neurocrine Clinical Site	Santa Clarita	California	United States	91321
6	Neurocrine Clinical Site	New Haven	Connecticut	United States	06510
7	Neurocrine Clinical Site	Boca Raton	Florida	United States	33431
8	Neurocrine Clinical Site	Gulf Breeze	Florida	United States	32561
9	Neurocrine Clinical Site	Hialeah	Florida	United States	33013
10	Neurocrine Clinical Site	Orlando	Florida	United States	32801
11	Neurocrine Clinical Site	Orlando	Florida	United States	32803
12	Neurocrine Clinical Site	Saint Petersburg	Florida	United States	33701
13	Neurocrine Clinical Site	Tampa	Florida	United States	33614
14	Neurocrine Clinical Site	Chicago	Illinois	United States	60634
15	Neurocrine Clinical Site	Naperville	Illinois	United States	60563
16	Neurocrine Clinical Site	Iowa City	Iowa	United States	52242
17	Neurocrine Clinical Site	Leawood	Kansas	United States	66206
18	Neurocrine Clinical Site	Ann Arbor	Michigan	United States	48105
19	Neurocrine Clinical Site	Bloomfield Hills	Michigan	United States	48371
20	Neurocrine Clinical Site	Saint Louis	Missouri	United States	63110
21	Neurocrine Clinical Site	Lincoln	Nebraska	United States	68526
22	Neurocrine Clinical Site	Nashua	New Hampshire	United States	03060
23	Neurocrine Clinical Site	Mount Arlington	New Jersey	United States	07856
24	Neurocrine Clinical Site	Voorhees	New Jersey	United States	08043
25	Neurocrine Clinical Site	Bronx	New York	United States	10467
26	Neurocrine Clinical Site	New York	New York	United States	10036
27	Neurocrine Clinical Site	Durham	North Carolina	United States	27705
28	Neurocrine Clinical Site	Mason	Ohio	United States	45040
29	Neurocrine Clinical Site	Oklahoma City	Oklahoma	United States	73112
30	Neurocrine Clinical Site	Charleston	South Carolina	United States	29414
31	Neurocrine Clinical Site	Dallas	Texas	United States	75243
32	Neurocrine Clinical Site	Houston	Texas	United States	77030
33	Neurocrine Clinical Site	Houston	Texas	United States	77058
34	Neurocrine Clinical Site	San Antonio	Texas	United States	78249
35	Neurocrine Clinical Site	Everett	Washington	United States	98201
36	Neurocrine Clinical Site	Tacoma	Washington	United States	98405
37	Neurocrine Clinical Site	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• Neurocrine Biosciences

Investigators

• Study Director: Clinical Development Lead, Neurocrine Biosciences

Study Documents (Full-Text)

• Study Protocol - Nov 6, 2017
• Statistical Analysis Plan - Feb 19, 2020

More Information

Publications

• Farber RH, Angelov A, Kim K, Carmack T, Thai-Cuarto D, Roberts E. Clinical development of valbenazine for tics associated with Tourette syndrome. Expert Rev Neurother. 2021 Apr;21(4):393-404. doi: 10.1080/14737175.2021.1898948. Epub 2021 Apr 1. Review.

• Responsible Party: Neurocrine Biosciences
• ClinicalTrials.gov Identifier: NCT03444038
• Other Study ID Numbers: NBI-98854-TS2004
• First Posted: Feb 23, 2018
• Last Update Posted: Feb 23, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tourette Syndrome; Syndrome

Study Results

Participant Flow

Recruitment Details	Up to 120 male and female pediatric participants, 6 to 18 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4th or 5th Editions (DSM-IV or -5) diagnosis of Tourette Syndrome, were planned to be enrolled. A total of 85 participants were enrolled and received at least 1 dose of study treatment.

Arm/Group Title	Valbenazine
Arm/Group Description	Participants received valbenazine once daily for up to 24 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 participants <50 kg and 80 mg for participants ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Period Title: Overall Study
STARTED	85
COMPLETED	56
NOT COMPLETED	29

Baseline Characteristics

Arm/Group Title	Valbenazine
Arm/Group Description	Participants received valbenazine once daily for up to 24 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 participants <50 kg and 80 mg for participants ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Overall Participants	85
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.6 (2.6)
Sex: Female, Male (Count of Participants)
Female	16 18.8%
Male	69 81.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	25 29.4%
Not Hispanic or Latino	60 70.6%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 3.5%
Native Hawaiian or Other Pacific Islander	1 1.2%
Black or African American	6 7.1%
White	72 84.7%
More than one race	0 0%
Other	3 3.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	A TEAE is an adverse event not present prior to the initiation of study drug dosing, or is an already present event that worsens either in intensity or frequency following the initiation of study drug dosing. All qualifying TEAE are reported regardless of threshold.
Time Frame	Baseline through Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valbenazine
Arm/Group Description	Participants received valbenazine once daily for up to 24 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 participants <50 kg and 80 mg for participants ≥50 kg to achieve an optimal dose of valbenazine for each participant.
Measure Participants	85
Count of Participants [Participants]	71 83.5%

Adverse Events

Time Frame	From baseline up to Week 28.
Arm/Group Title	Valbenazine
Arm/Group Description	Participants received valbenazine once daily for up to 24 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 participants <50 kg and 80 mg for participants ≥50 kg to achieve an optimal dose of valbenazine for each participant.
All Cause Mortality
	Valbenazine
	Affected / at Risk (%)	# Events
Total	0/85 (0%)
Serious Adverse Events
	Valbenazine
	Affected / at Risk (%)	# Events
Total	3/85 (3.5%)
Infections and infestations
Infected bites	1/85 (1.2%)
Nervous system disorders
Cognitive disorder	1/85 (1.2%)
Skin and subcutaneous tissue disorders
Henoch-Schonlein purpura	1/85 (1.2%)
Other (Not Including Serious) Adverse Events
	Valbenazine
	Affected / at Risk (%)	# Events
Total	50/85 (58.8%)
Gastrointestinal disorders
Abdominal pain upper	5/85 (5.9%)
Nausea	9/85 (10.6%)
General disorders
Fatigue	11/85 (12.9%)
Irritability	8/85 (9.4%)
Nervous system disorders
Headache	9/85 (10.6%)
Sedation	10/85 (11.8%)
Somnolence	17/85 (20%)
Psychiatric disorders
Depression	5/85 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Generally, the PI has the right to publish results provided such publication does not violate confidentiality or IP provisions within the contract with the Sponsor. Prior to submission for publication or presentation of results, the PI must provide the Sponsor time for review. The Sponsor can request the PI to withhold or remove information from all publications. For a multi-center study, any publication of results by the PI shall not be made before the first multi-center publication.