A Study to Test if TEV-50717 is Safe and Effective in Relieving Abnormal Involuntary Movements in Cerebral Palsy

NCT04200352 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: TV50717-CNS-300812019-001807-19
• Study Type: interventional
• Target: 44
• Locations: 9 countries
• Sites: 30

Brief Summary

Study TV50717-CNS-30081 is a 55-week study in which participants who have successfully completed the parent study (Study TV50717-CNS-30080) may be eligible to enroll in this study. The primary objective of this study is to evaluate the safety and tolerability of long-term therapy with TEV-50717 in children and adolescents with DCP. The secondary objective of this study is to evaluate the efficacy of long-term therapy with TEV-50717 in reducing the severity of DCP.

Conditions

Cerebral Palsy, Dyskinetic

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Adverse Events (AEs)

  Adverse events can include any of the following: clinically significant vital signs, ECG parameters, or laboratory parameters. An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.

  Baseline up to Week 55

• Number of Participants (Aged ≥12 Years) With Columbia-Suicide Severity Rating Scale (C-SSRS) Outcomes (Worst Overall Finding)

  Participants were placed into categories for suicidal ideation or behavior and non-suicidal self-injurious behavior based on their responses to various questions. For suicidal ideation or behavior, the following categories were used: None; Wish to be dead; Non-specific active suicidal thoughts; Any methods (not plan) without intent to act; Some intent to act, without specific plan; Specific plan and intent; Preparatory acts or behavior; Aborted attempt; Interrupted attempt; Actual attempt; and Suicide. For non-suicidal self-injurious behavior, the following categories were used: No or yes. Number of participants with worst overall finding of suicidal ideation or suicidal behavior and non-suicidal self-injurious behavior from Baseline to Week 54 are reported.

  Baseline to Week 54

• Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale I Total Score at Week 54

  The ESRS subscale I is a 7-item subjective questionnaire to evaluate parkinsonism, akathisia, dystonia and dyskinesia. The ESRS I is scored on a 4-point scale (0=absent, 1=Mild, 2=Moderate, 3=Severe) for each item. The evaluation takes into account the verbal report of the participant on 1) the frequency and duration of the symptom during the day, 2) the number of days the symptom was present during the last week, and 3) the subjective evaluation of the intensity of the symptom by the participant. Total score was the sum of the 7 items which ranges from 0 (absent) to 28 (severe). Higher scores indicate greater severity of disorder.

  Baseline, Week 54

• Change From Baseline in ESRS Subscale II Total Score at Week 54

  The ESRS subscale II is a 17-item questionnaire to evaluate parkinsonism and akathisia. The ESRS II consists of the following parts: tremor (0 \[none\]-48 \[severe\]), gait and posture (0 \[none\]-6 \[severe\]), postural stability (0 \[none\]-6 \[severe\]), rigidity (0 \[none\]-24 \[severe\]), expressive automatic movements (0 \[none\]-6 \[severe\]), bradykinesia (0 \[none\]-6 \[severe\]), and akathisia (0 \[none\]-6 \[severe\]). Total score was the sum of the 17 items ranging from 0 (absent) to 102 (severe). Higher scores indicate greater severity of disorder.

  Baseline, Week 54

• Change From Baseline in Child Behavior Checklist (CBCL) Competence Total Score at Week 53

  The CBCL assesses behavioral and emotional status in children ages 6 through 18 years of age as reported by the caregiver. The full CBCL has two parts, a Competence Scale (Parts I to VII) and a Syndrome Scale (behavioral items). The Competence Scale (Parts I to VII) assesses various activities (for example, sports, hobbies, games, organizations, clubs, teams, groups, jobs, and chores), interpersonal relationships, and academic performance. The checklists having 120 questions consist of a number of statements about the child's behavior and responses which are recorded on a scale: 0 = Not True; 1 = Somewhat or Sometimes True; 2 = Very True or Often True. CBCL competence total score ranged from 0 (no problem) to 240 (lesser problem), which was calculated by adding individual scores of each domain. Higher scores indicate greater problems in child behavior.

  Baseline, Week 53

• Change From Baseline in CBCL Syndrome Total Score at Week 53

  The CBCL assesses behavioral and emotional status in children ages 6 through 18 years of age as reported by the caregiver. The full CBCL has two parts, a Competence Scale (Parts I to VII) and a Syndrome Scale (behavioral items). The Syndrome Scale comprises 113 questions related to problem behaviors. For each item, the responses are recorded on a scale: 0 = Not True; 1 = Somewhat or Sometimes True; 2 = Very True or Often True. The problem behaviors are scored on the following 8 empirically based syndromes: anxious/depressed, withdrawn/depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior, and aggressive behavior. CBCL syndrome total score ranged from 0 (no problem) to 226 (lesser problem), which was calculated by adding individual scores of each domain. Higher scores indicate greater problems in child behavior.

  Baseline, Week 53

• Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 54

  The ESS is a self-administered questionnaire composed of 8 questions that provide a measure of a participant's general level of daytime sleepiness. The ESS is composed of 8 items. The responders were asked to rate their chances of falling asleep while engaged at 8 different activities, on a 4-point scale: 0 = would never fall asleep; 1=slight chance of falling asleep; 2=moderate chance of falling asleep; 3=high chance of falling asleep. Total score was calculated as the sum of 8 item scores ranging from 0 (never) to 24 (high chance of falling asleep). Higher scores indicate high chances of falling asleep.

  Baseline, Week 54

Secondary Outcomes (16)

• Change From Baseline in the Movement Disorder-Childhood Rating Scale (MD-CRS) Part I Total Score (General Assessment, Centrally Read)

  Baseline, Week 53, Week 54

• Change From Baseline in the MD-CRS Part II Total Score (Movement Disorder Severity, Centrally Read)

  Baseline, Week 53, Week 54

• Change From Baseline in the MD-CRS Part I Total Score (General Assessment, Physician Rated)

  Baseline, Week 53, Week 54

• Change From Baseline in the MD-CRS Part II Total Score (General Assessment, Physician Rated)

  Baseline, Week 53, Week 54

• Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Physician Rated)

  Baseline, Week 53, Week 54

Study Arms (1)

TEV-50717

EXPERIMENTAL

The dose of the TEV-50717 should be increased on a weekly basis to reach a clinically meaningful reduction in dyskinesia, as indicated by a reduction in the Clinical Global Impression of Improvement;(CGI-I).

Drug: TEV-50717

Interventions

TEV-50717 DRUG

Oral tablets are 6, 9, and 12 mg.

Also known as: Deutetrabenazine, SD-809

TEV-50717

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant has completed parent Study TV50717-CNS-30080.
• Participant weighs at least 12 kg (26 lb) on day 1 of this study.
• Participant is able to swallow TEV-50717 whole. NOTE- Additional criteria apply, please contact the investigator for more information

You may not qualify if:

• Participant has clinically significant depression at screening or day 1 of this study. Note: Participants receiving antidepressant therapy may be enrolled if on a stable dose for at least 6 weeks before screening or day 1 (whichever comes first) and anticipated to remain stable (dose and frequency) within the study duration.
• Participant has a history of suicidal intent or related behaviors based on medical or psychiatric history or the C-SSRS at screening visit, if performed, or at the day 1 visit, as applicable according to the participant's age:
• intent to act on suicidal ideation with a specific plan, irrespective of level of ambivalence, at the time of suicidal thought
• 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.
• within 30 days: tetrabenazine or valbenazine
• within 21 days: reserpine
• within 14 days: levodopa, dopamine agonists, and monoamine oxidase inhibitors
• Participant has received treatment with stem cells, deep brain stimulation, transmagnetic stimulation, or transcranial direct current stimulation for treatment of abnormal movements or CP since the week 15 visit of Study TV50717-CNS-30080, or the participant is not in a stable clinical condition.
• Participants with a history of torsade de pointes, congenital long QT syndrome, bradyarrhythmias, other cardiac arrhythmias, or uncompensated heart failure.
• Participant has a known allergy to any of the components of TEV-50717.
• Participant has participated in an investigational drug or device study other than Study TV50717-CNS-30080 and received IMP/intervention within 30 days or 5 drug half-lives of day 1 of this study, whichever is longer.
• Participant is pregnant or breastfeeding. NOTE- Additional criteria apply, please contact the investigator for more information

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (30)

Teva Investigational Site 14137

Birmingham, Alabama, 35233, United States

Location

Teva Investigational Site 14295

San Diego, California, 92123, United States

Location

Teva Investigational Site 14122

Voorhees Township, New Jersey, 08043, United States

Location

Teva Investigational Site 14299

Charleston, South Carolina, 29414, United States

Location

Teva Investigational Site 14129

Nashville, Tennessee, 37232, United States

Location

Teva Investigational Site 39058

Blegdamsvej 9, 2100, Denmark

Location

Teva Investigational Site 80146

Tel-Aviv, Tel-Aviv District, 64239, Israel

Location

Teva Investigational Site 80147

Zerifin, Central District, 70300, Israel

Location

Teva Investigational Site 30214

Milan, 20133, Italy

Location

Teva Investigational Site 30216

Pisa, 56018, Italy

Location

Teva Investigational Site 53434

Gdansk, 80-952, Poland

Location

Teva Investigational Site 53428

Gdansk, Pomerania Province, 80-389, Poland

Location

Teva Investigational Site 53427

Krakow, 30-534, Poland

Location

Teva Investigational Site 53430

Wiazowna, Mazovia Province, 05-462, Poland

Location

Teva Investigational Site 50477

Kazan', 420021, Russia

Location

Teva Investigational Site 50475

Khabarovsk, Khabarovsk Krai Region, 680013, Russia

Location

Teva Investigational Site 50470

Moscow, Moscow Region, 129110, Russia

Location

Teva Investigational Site 50485

Nizhniy Novgorod, Nizhny Novgorod Region, 603126, Russia

Location

Teva Investigational Site 50468

Novosibirsk, Novosibirsk Region, 630047, Russia

Location

Teva Investigational Site 50469

Smolensk, Smolensk Region, 214018, Russia

Location

Teva Investigational Site 50478

Stavropol, Stavropol Krai Region, 355000, Russia

Location

Teva Investigational Site 50474

Tyumen, Tyumen Region, 625023, Russia

Location

Teva Investigational Site 31254

Valencia, 46026, Spain

Location

Teva Investigational Site 58313

Dnipro, Dnipropetrovsk Province, 49101, Ukraine

Location

Teva Investigational Site 58309

Kyiv, Kyiv Province, 04209, Ukraine

Location

Teva Investigational Site 58311

Odessa, Odessa Province, 65012, Ukraine

Location

Teva Investigational Site 58310

Vinnytsya, Vinnytsia Province, 21005, Ukraine

Location

Teva Investigational Site 34245

Edinburgh, Edinburgh, EH16 4TJ, United Kingdom

Location

Teva Investigational Site 34243

London, Greater London, SE1 7EH, United Kingdom

Location

Teva Investigational Site 34244

Sheffield, South Yorkshire, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

Cerebral Palsy

Interventions

deutetrabenazine

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

The study was terminated early due to failure of TV50717-CNS-30080 (parent study) to meet the primary efficacy endpoint.

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

USMedInfo@tevapharm.com

888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 16, 2019
• Study Start: February 4, 2020
• Primary Completion: February 14, 2023
• Study Completion: February 14, 2023
• Last Updated: April 22, 2024
• Results First Posted: April 22, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (5); PL (4); IT (2); UA (4); IL (2); DK (1); GB (3); ES (1); RU (8)