A Study of TEV-50717 (Deutetrabenazine) for the Treatment of Dyskinesia in Cerebral Palsy in Children and Adolescents

NCT03813238 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: TV50717-CNS-300802018-003742-17
• Study Type: interventional
• Target: 63
• Locations: 12 countries
• Sites: 70

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.

Conditions

Cerebral Palsy, Dyskinetic

Keywords

DCP

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Movement Disorder-Childhood Rating Scale (MD-CRS) Part II Total Score (Movement Disorder Severity, Centrally Read) at Week 15

  MD-CRS part II evaluates the severity of movement disorder in a scale of 0 to 4 in 7 body regions, all areas in which dyskinesia can be seen. All items were scored by the rater in the clinic and were centrally read based on video recording. In rating the movement disorder of body part, 0 refers to absence of a movement disorder and 4 refers to a situation where movement disorder is present during all of the tasks for the region examined and/or involves 3 or more of the other regions, making completion impossible. The 7 body regions are (i) eye and periorbital region, (ii) face, (iii) tongue and perioral region, (iv) neck, (v) trunk, (vi) upper limb, and (vii) lower limb. Total score was obtained by summing the individual items scores and ranges from 0 (absent of a movement disorder) to 28 (marked/prolonged movement disorder), with higher scores indicating more movement disorder. Least square (LS) mean and standard error (SE) was calculated using a mixed-model repeated-measures (MMRM).

  Baseline, Week 15

Secondary Outcomes (28)

• Change From Baseline in the MD-CRS Part I Total Score (General Assessment, Centrally Read) at Week 15

  Baseline, Week 15

• Caregiver Global Impression of Improvement (CaGI-I) Scale Score (Global, Caregiver Rated) at Week 15

  Week 15

• Clinical Global Impression of Improvement (CGI-I) Scale Score (Global, Physician Rated) at Week 15

  Week 15

• Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC) Score (Centrally Read) at Week 15

  Baseline, Week 15

• Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Dystonia (UHDRS-TMD) Score (Centrally Read) at Week 15

  Baseline, Week 15

Study Arms (2)

TEV-50717

EXPERIMENTAL

administered as oral tablets at a starting dose of 6 mg once daily

Drug: TEV-50717

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

TEV-50717 DRUG

Dosage ranging from 6 mg to 48 mg.

Also known as: Deutetrabenazine, (previously SD-809)

TEV-50717

Placebo DRUG

Dosage ranging from 6 mg to 48 mg.

Placebo

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 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

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (70)

Teva Investigational Site 14137

Birmingham, Alabama, 35233, United States

Location

Teva Investigational Site 14224

Phoenix, Arizona, 85016, United States

Location

Teva Investigational Site 14227

Loma Linda, California, 92354, United States

Location

Teva Investigational Site 14295

San Diego, California, 92123, United States

Location

Teva Investigational Site 14293

Washington D.C., District of Columbia, 20010, United States

Location

Teva Investigational Site 14127

Miami, Florida, 33155, United States

Location

Teva Investigational Site 14125

Tampa, Florida, 33609, United States

Location

Teva Investigational Site 14136

Atlanta, Georgia, 30318, United States

Location

Teva Investigational Site 14291

Atlanta, Georgia, 30328, United States

Location

Teva Investigational Site 14130

Savannah, Georgia, 31406, United States

Location

Teva Investigational Site 14290

New Orleans, Louisiana, 70118-5720, United States

Location

Teva Investigational Site 14226

Saint Paul, Minnesota, 55101, United States

Location

Teva Investigational Site 14134

Lincoln, Nebraska, 68526, United States

Location

Teva Investigational Site 14122

Gibbsboro, New Jersey, 08026, United States

Location

Teva Investigational Site 14297

New Brunswick, New Jersey, 08901, United States

Location

Teva Investigational Site 14225

New York, New York, 10032, United States

Location

Teva Investigational Site 14123

Rochester, New York, 14642, United States

Location

Teva Investigational Site 14348

Portland, Oregon, 97239, 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 14228

Houston, Texas, 77030, United States

Location

Teva Investigational Site 14223

Richmond, Virginia, 23298, United States

Location

Teva Investigational Site 14135

Everett, Washington, 98201, United States

Location

Teva Investigational Site 37100

Luxembourg City, 1210, Belgium

Location

Teva Investigational Site 37102

Woluwe-Saint-Lambert, 1200, Belgium

Location

Teva Investigational Site 11165

Nepean, Ontario, K2G 1W2, Canada

Location

Teva Investigational Site 39058

Copenhagen, 2100, Denmark

Location

Teva Investigational Site 80144

Jerusalem, 9103102, Israel

Location

Teva Investigational Site 80145

Safed, 13100, Israel

Location

Teva Investigational Site 80146

Tel Aviv, 6423906, Israel

Location

Teva Investigational Site 80147

Ẕerifin, 70300, Israel

Location

Teva Investigational Site 30217

Florence, 50139, Italy

Location

Teva Investigational Site 30214

Milan, 20133, Italy

Location

Teva Investigational Site 30213

Napoli, 80138 -, Italy

Location

Teva Investigational Site 30216

Pisa, 56018, Italy

Location

Teva Investigational Site 30215

Roma, 00168, Italy

Location

Teva Investigational Site 30212

Roma, 00185, Italy

Location

Teva Investigational Site 53434

Gdansk, 80-211, Poland

Location

Teva Investigational Site 53428

Gdansk, 80-389, Poland

Location

Teva Investigational Site 53433

Gmina Strzelin, 57100, Poland

Location

Teva Investigational Site 53427

Krakow, 30-539, Poland

Location

Teva Investigational Site 53431

Lublin, 20-828, Poland

Location

Teva Investigational Site 53432

Poznan, 60-693, Poland

Location

Teva Investigational Site 53430

Wiązowna, 05-462, Poland

Location

Teva Investigational Site 50477

Kazan', 420021, Russia

Location

Teva Investigational Site 50475

Khabarovsk, 680013, Russia

Location

Teva Investigational Site 50473

Moscow, 117513, Russia

Location

Teva Investigational Site 50470

Moscow, 129110, Russia

Location

Teva Investigational Site 50485

Nizhny Novgorod, 603950, Russia

Location

Teva Investigational Site 50468

Novosibirsk, 630091, Russia

Location

Teva Investigational Site 50469

Smolensk, 214018, Russia

Location

Teva Investigational Site 50478

Stavropol, 999999, Russia

Location

Teva Investigational Site 50474

Tyumen, 625023, Russia

Location

Teva Investigational Site 62054

Banská Bystrica, 974 04, Slovakia

Location

Teva Investigational Site 62053

Dubnica nad Váhom, 01841, Slovakia

Location

Teva Investigational Site 31259

Córdoba, 14011, Spain

Location

Teva Investigational Site 31256

Granada, 18013, Spain

Location

Teva Investigational Site 31255

Madrid, 28009, Spain

Location

Teva Investigational Site 31257

Madrid, 28046, Spain

Location

Teva Investigational Site 31258

Seville, 41015, Spain

Location

Teva Investigational Site 31254

Valencia, 46026, Spain

Location

Teva Investigational Site 58313

Dnipropetrovsk, 49027, Ukraine

Location

Teva Investigational Site 58312

Kharkiv, 61068, Ukraine

Location

Teva Investigational Site 58309

Kyiv, 04209, Ukraine

Location

Teva Investigational Site 58311

Odesa, 65012, Ukraine

Location

Teva Investigational Site 58310

Vinnytsia, 21037, Ukraine

Location

Teva Investigational Site 34246

Bristol, BS2 8BJ, United Kingdom

Location

Teva Investigational Site 34245

Edinburgh, EH9 1LF, United Kingdom

Location

Teva Investigational Site 34243

London, SE1 7EH, United Kingdom

Location

Teva Investigational Site 34244

Sheffield, 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

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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: January 23, 2019
• Study Start: August 6, 2019
• Primary Completion: July 5, 2022
• Study Completion: July 21, 2022
• Last Updated: September 8, 2023
• Results First Posted: September 8, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

US (23); BE (2); PL (7); CA (1); SL (2); GB (4); IT (6); DK (1); RU (9); ES (6); UA (5); IL (4)