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

NCT03530293 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: NBI-98854-TS2005
• Study Type: interventional
• Target: 81
• Locations: 2 countries
• Sites: 49

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.

Conditions

Tourette Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the YGTSS TTS

  Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization

• Change From Randomization Baseline to the Week 36 Visit in the YGTSS TTS

  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

  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

  Randomization Baseline (Week 8, 10 or 12); Week 36

Study Arms (3)

Pre-randomization Valbenazine

EXPERIMENTAL

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

Randomized Placebo

PLACEBO COMPARATOR

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

Randomized Valbenazine

EXPERIMENTAL

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

Interventions

Valbenazine DRUG

vesicular monoamine transporter 2 (VMAT2) inhibitor

Also known as: NBI-98854

Pre-randomization Valbenazine; Randomized Valbenazine

Placebo oral capsule DRUG

non-active dosage form

Randomized Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Neurocrine Biosciences: lead

Study Sites (49)

Neuricrine Clinical Site

Sun City, Arizona, 85351, United States

Location

Neurocrine Clinical Site

Little Rock, Arkansas, 72205, United States

Location

Neurocrine Clinical Site

Rogers, Arkansas, 72758, United States

Location

Neurocrine Clinical Site

Anaheim, California, 92805, United States

Location

Neurocrine Clinical Site

Fullerton, California, 92835, United States

Location

Neurocrine Clinical Site

San Diego, California, 92108, United States

Location

Neurocrine Clinical Site

Santa Ana, California, 92705, United States

Location

Neurocrine Clinical Site

Pueblo, Colorado, 81003, United States

Location

Neurocrine Clinical Site

Stamford, Connecticut, 06905, United States

Location

Neurocrine Clinical Site

Washington D.C., District of Columbia, 22207, United States

Location

Neurocrine Clinical Site

Gulf Breeze, Florida, 32561, United States

Location

Neurocrine Clinical Site

Hialeah, Florida, 33012, United States

Location

Neurocrine Clinical Site

Miami, Florida, 33125, United States

Location

Neurocrine Clinical Site

Miami, Florida, 33136, United States

Location

Neurocrine Clinical Site

North Miami, Florida, 33161, United States

Location

Neurocrine Clinical Site

Orlando, Florida, 32803, United States

Location

Neurocrine Clinical Site

Palmetto Bay, Florida, 33157, United States

Location

Neurocrine Clinical Site

Spring Hill, Florida, 34609, United States

Location

Neurocrine Clinical Site

St. Petersburg, Florida, 33701, United States

Location

Neurocrine Clinical Site

Tallahassee, Florida, 32308, United States

Location

Neurocrine Clinical Site

Atlanta, Georgia, 30338, United States

Location

Neurocrine Clinical Site

Fayetteville, Georgia, 30214, United States

Location

Neurocrine Clinical Site

Savannah, Georgia, 31406, United States

Location

Neurocrine Clinical Site

Chicago, Illinois, 60634, United States

Location

Neurocrine Clinical Site

South Bend, Indiana, 46617, United States

Location

Neurocrine Clinical Site

Boston, Massachusetts, 02114, United States

Location

Neurocrine Clinical Site

Ann Arbor, Michigan, 48015, United States

Location

Neurocrine Clinical Site

Bloomfield Hills, Michigan, 48302, United States

Location

Neurocrine Clinical Site

West Bloomfield, Michigan, 48322, United States

Location

Neurocrine Clinical Site

Lincoln, Nebraska, 68526, United States

Location

Neurocrine Clinical Site

Nashua, New Hampshire, 03060, United States

Location

Neurocrine Clinical Site

Cherry Hill, New Jersey, 08002, United States

Location

Neurocrine Clinical Site

Mount Arlington, New Jersey, 07856, United States

Location

Neurocrine Clinical Site

New York, New York, 10036, United States

Location

Neurocrine Clinical Site

South Setauket, New York, 11720, United States

Location

Neurocrine Clinical Site

Charlotte, North Carolina, 29141, United States

Location

Neurocrine Clinical Site

Mason, Ohio, 45040, United States

Location

Neurocrine Clinical Site

Oklahoma City, Oklahoma, 73112, United States

Location

Neurocrine Clinical Site

Dallas, Texas, 75243, United States

Location

Neurocrine Clinical Site

DeSoto, Texas, 75115, United States

Location

Neurocrine Clinical Site

Houston, Texas, 77030, United States

Location

Neurocrine Clinical Site

Houston, Texas, 77058, United States

Location

Neurocrine Clinical Site

Irving, Texas, 75062, United States

Location

Neurocrine Clinical Site

San Antonio, Texas, 78249, United States

Location

Neurocrine Clinical Site

Charlottesville, Virginia, 22903, United States

Location

Neurocrine Clinical Site

Bothell, Washington, 98011, United States

Location

Neurocrine Clinical Site

Everett, Washington, 98201, United States

Location

Neurocrine Clinical Site

Spokane, Washington, 99202, United States

Location

Neurocrine Clinical Site

San Juan, 00926, Puerto Rico

Location

MeSH Terms

Conditions

Tourette Syndrome

Interventions

valbenazine

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tic Disorders; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Neurocrine Medical Information
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Study Officials

• Clinical Development Lead

  Neurocrine Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: open-label study drug treatment period followed by blinded randomization into treatment arm or placebo arm
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: May 21, 2018
• Study Start: April 17, 2018
• Primary Completion: July 16, 2019
• Study Completion: July 16, 2019
• Last Updated: May 17, 2022
• Results First Posted: May 17, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (48)