Clinical trial NCT03813238: A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Dyskinesia in Cerebral Palsy in Children and Adolescents
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of TEV-50717 (Deutetrabenazine) for the Treatment of Dyskinesia in Cerebral Palsy in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cerebral Palsy, Dyskinetic
Keywords: DCP
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-23
Enrollment: 63
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: CP (cerebral palsy) refers to a group of neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination. CP is caused by damage to or abnormalities inside the developing brain that disrupt the brain's ability to control movement and maintain posture and balance. The signs of CP usually appear in the early months of life, although specific diagnosis may be delayed until the age of 2 years or older. TEV-50717 (deutetrabenazine, also known as SD-809) has already provided evidence for safe and effective use in 2 other hyperkinetic movement disorders, namely chorea in Huntington's disease (HD) and tardive dyskinesia (TD). Currently, there is no approved treatment available for Dyskinesia in cerebral palsy (DCP). The available treatment options address some of the manifestations of DCP. The study population will include pediatric and adolescent participants (6 through 18 years of age) with DCP with predominant choreiform movement disorder, who have had nonprogressive CP symptoms since infancy (≤2 years of age). Diagnosis of DCP is based on the Surveillance of Cerebral Palsy in Europe criteria.

This is a Phase 3 study that will evaluate the efficacy and safety of TEV-50717 administered as oral tablets at a starting dose of 6 mg once daily in participants (age 6 through 18 years, inclusive) with DCP with predominant choreiform movement disorder. The study will be conducted in multiple centers and will use 2 parallel treatment groups (ie, TEV-50717 and placebo) in which participants will be randomized in a 2:1 ratio.

"Predominant" in this instance indicates that the choreiform movement disorder is the main cause of impairment or distress.


Eligibility criteria: Inclusion Criteria:

* Participant is 6 through 18 years of age (inclusive) at baseline.
* Participant weighs at least 26 pounds (12 kg) at baseline.
* Participant has had CP symptoms since infancy (≤2 years)
* Choreiform is the prevalent movement disorder as assessed by the EAB at screening.
* Participant has a diagnosis of DCP
* Participant is able to swallow study medication whole.
* Females who are postmenarchal or ≥12 years of age whose male partners are potentially fertile (ie, no vasectomy) must use highly effective birth control methods for the duration of the study
* Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

* Participant has a predominant movement disorder other than dyskinesia.
* Participant's predominant motor symptoms are dystonic.
* Participant's predominant motor symptoms are spastic.
* Participant has choreiform movement disorder that has not been consistent throughout the life of the participant.
* Participant has clinically significant depression at screening or baseline.
* Note: Participants receiving antidepressant therapy may be enrolled if on a stable dose for at least 6 weeks before screening.
* Participant has a history of suicidal intent or related behaviors within 2 years of screening:
* Previous intent to act on suicidal ideation with a specific plan, irrespective of level of ambivalence, at the time of suicidal thought
* Previous suicidal preparatory acts or behavior
* Participant has a history of a previous actual, interrupted, or aborted suicide attempt.
* Participant has a first-degree relative who has completed suicide.
* Participant has received treatment with stem cells, deep brain stimulation, transmagnetic stimulation, or transcranial direct current stimulation for treatment of abnormal movements or CP within 6 months of the screening visit, or the participant is not in a stable clinical condition.
* Participant has recent surgical procedure or is anticipated to have a surgical procedure during the study that, in the opinion of the investigator, makes the Participant unsuitable for the study.
* Participant has a severe mental disability or an unstable or serious medical illness (eg, epilepsy) at screening or baseline that, in the opinion of the investigator, could jeopardize or would compromise the Participant's ability to participate in this study.
* Participant has a known allergy to any of the components of the investigational medicinal product (IMP).
* Participant is pregnant or breastfeeding.
* Participant has a history of or acknowledges alcohol or substance abuse in the 12 months before screening
* Participants with a history of torsade de pointes, congenital long QT syndrome, bradyarrhythmias, other cardiac arrhythmias, or uncompensated heart failure.
* Additional criteria apply, please contact the investigator for more information

Primary outcomes:
measure: Change From Baseline in the Movement Disorder-Childhood Rating Scale (MD-CRS) Part II Total Score (Movement Disorder Severity, Centrally Read) at Week 15
timeFrame: Baseline, Week 15
Secondary outcomes:
measure: Change From Baseline in the MD-CRS Part I Total Score (General Assessment, Centrally Read) at Week 15
timeFrame: Baseline, Week 15
measure: Caregiver Global Impression of Improvement (CaGI-I) Scale Score (Global, Caregiver Rated) at Week 15
timeFrame: Week 15
measure: Clinical Global Impression of Improvement (CGI-I) Scale Score (Global, Physician Rated) at Week 15
timeFrame: Week 15
measure: Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC) Score (Centrally Read) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Dystonia (UHDRS-TMD) Score (Centrally Read) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in the MD-CRS Part I Total Score (General Assessment, Physician Rated) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in the MD-CRS Part II Total Score (General Assessment, Physician Rated) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Physician Rated) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Centrally Read) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in UHDRS-TMS Score (Physician Rated) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in UHDRS-TMC Score (Physician Rated) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in UHDRS-TMD Score (Physician Rated) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in Pediatric Evaluation Disability Inventory-Computer Adapted Test (PEDI-CAT) Score (Activities of Daily Living [ADL], Caregiver Completed, Content-Balanced Version) at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in the CP Module of the Pediatric Quality of Life Inventory (PedsQL) Total Score (Quality of Life [QoL], Participant/Caregiver) at Week 15
timeFrame: Baseline, Week 15
measure: Patient Global Impression of Improvement (PGI-I) Scale Score (Global, Participant/Caregiver) at Week 15
timeFrame: Week 15
measure: Change From Baseline in Clinical Global Impression of Severity (CGI-S) Scale Score (Global, Physician Rated) at Week 15
timeFrame: Baseline, Week 15
measure: Number of Participants With CaGI-I Response
timeFrame: Week 15
measure: Number of Participants With CGI-I Response
timeFrame: Week 15
measure: Number of Participants With CGI-S Response
timeFrame: Week 15
measure: Number of Participants With PGI-I Response
timeFrame: Week 15
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Week 17
measure: Number of Participants With Shift From Baseline to Week 15 in Electrocardiogram (ECG) Findings
timeFrame: Baseline to Week 15
measure: Change From Baseline in Child Behavior Checklist (CBCL) Competence Total Score at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in Child Behavior Checklist (CBCL) Syndrome Total Score at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale I Total Score at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale II Total Score at Week 15
timeFrame: Baseline, Week 15
measure: Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 15
timeFrame: Baseline, Week 15
measure: Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Outcomes (Suicidal Ideation and Suicidal Behavior) at Week 15
timeFrame: Week 15
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 14137
state: Alabama
city: Phoenix
country: United States
facility: Teva Investigational Site 14224
state: Arizona
city: Loma Linda
country: United States
facility: Teva Investigational Site 14227
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 14295
state: California
city: Washington
country: United States
facility: Teva Investigational Site 14293
state: District of Columbia
city: Miami
country: United States
facility: Teva Investigational Site 14127
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 14125
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 14136
state: Georgia
city: Atlanta
country: United States
facility: Teva Investigational Site 14291
state: Georgia
city: Savannah
country: United States
facility: Teva Investigational Site 14130
state: Georgia
city: New Orleans
country: United States
facility: Teva Investigational Site 14290
state: Louisiana
city: Saint Paul
country: United States
facility: Teva Investigational Site 14226
state: Minnesota
city: Lincoln
country: United States
facility: Teva Investigational Site 14134
state: Nebraska
city: Gibbsboro
country: United States
facility: Teva Investigational Site 14122
state: New Jersey
city: New Brunswick
country: United States
facility: Teva Investigational Site 14297
state: New Jersey
city: New York
country: United States
facility: Teva Investigational Site 14225
state: New York
city: Rochester
country: United States
facility: Teva Investigational Site 14123
state: New York
city: Portland
country: United States
facility: Teva Investigational Site 14348
state: Oregon
city: Charleston
country: United States
facility: Teva Investigational Site 14299
state: South Carolina
city: Nashville
country: United States
facility: Teva Investigational Site 14129
state: Tennessee
city: Houston
country: United States
facility: Teva Investigational Site 14228
state: Texas
city: Richmond
country: United States
facility: Teva Investigational Site 14223
state: Virginia
city: Everett
country: United States
facility: Teva Investigational Site 14135
state: Washington
city: Luxembourg City
country: Belgium
facility: Teva Investigational Site 37100
city: Woluwe-Saint-Lambert
country: Belgium
facility: Teva Investigational Site 37102
city: Nepean
country: Canada
facility: Teva Investigational Site 11165
state: Ontario
city: Copenhagen
country: Denmark
facility: Teva Investigational Site 39058
city: Jerusalem
country: Israel
facility: Teva Investigational Site 80144
city: Safed
country: Israel
facility: Teva Investigational Site 80145
city: Tel-Aviv
country: Israel
facility: Teva Investigational Site 80146
city: Zerifin
country: Israel
facility: Teva Investigational Site 80147
city: Firenze
country: Italy
facility: Teva Investigational Site 30217
city: Milan
country: Italy
facility: Teva Investigational Site 30214
city: Napoli
country: Italy
facility: Teva Investigational Site 30213
city: Pisa
country: Italy
facility: Teva Investigational Site 30216
city: Roma
country: Italy
facility: Teva Investigational Site 30215
city: Roma
country: Italy
facility: Teva Investigational Site 30212
city: Gdansk
country: Poland
facility: Teva Investigational Site 53434
city: Gdansk
country: Poland
facility: Teva Investigational Site 53428
city: Krakow
country: Poland
facility: Teva Investigational Site 53427
city: Lublin
country: Poland
facility: Teva Investigational Site 53431
city: Poznan
country: Poland
facility: Teva Investigational Site 53432
city: Strzelin
country: Poland
facility: Teva Investigational Site 53433
city: Wiazowna
country: Poland
facility: Teva Investigational Site 53430
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 50477
city: Khabarovsk
country: Russian Federation
facility: Teva Investigational Site 50475
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50473
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50470
city: Nizhniy Novgorod
country: Russian Federation
facility: Teva Investigational Site 50485
city: Novosibirsk
country: Russian Federation
facility: Teva Investigational Site 50468
city: Smolensk
country: Russian Federation
facility: Teva Investigational Site 50469
city: Stavropol
country: Russian Federation
facility: Teva Investigational Site 50478
city: Tyumen
country: Russian Federation
facility: Teva Investigational Site 50474
city: Banska Bystrica
country: Slovakia
facility: Teva Investigational Site 62054
city: Dubnica Nad Vahom
country: Slovakia
facility: Teva Investigational Site 62053
city: Cordoba
country: Spain
facility: Teva Investigational Site 31259
city: Granada
country: Spain
facility: Teva Investigational Site 31256
city: Madrid
country: Spain
facility: Teva Investigational Site 31255
city: Madrid
country: Spain
facility: Teva Investigational Site 31257
city: Sevilla
country: Spain
facility: Teva Investigational Site 31258
city: Valencia
country: Spain
facility: Teva Investigational Site 31254
city: Dnipropetrovsk
country: Ukraine
facility: Teva Investigational Site 58313
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 58312
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58309
city: Odesa
country: Ukraine
facility: Teva Investigational Site 58311
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 58310
city: Bristol
country: United Kingdom
facility: Teva Investigational Site 34246
city: Edinburgh
country: United Kingdom
facility: Teva Investigational Site 34245
city: London
country: United Kingdom
facility: Teva Investigational Site 34243
city: Sheffield
country: United Kingdom
facility: Teva Investigational Site 34244
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: