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

Primary Purpose

Cerebral Palsy, Dyskinetic

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

TEV-50717

Placebo

About this trial

This is an interventional treatment trial for Cerebral Palsy, Dyskinetic focused on measuring DCP

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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 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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TEV-50717

Placebo

Arm Description

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

Matching placebo

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

The MD-CRS part I evaluates the impact of dyskinesia in cerebral palsy (DCP) on the activities of the participant and provides a general assessment of the movement disorder of motor function (7 items), oral/verbal function (3 items), self-care (3 items), and attention/alertness (2 items) on a scale of 0 (present) to 4 (absent). All items were scored by the rater in the clinic and were centrally read based on video recording. The total score was obtained by summing the individual items scores and ranges from 0 (marked/prolonged disorder) to 60 (absent of a disorder), with higher scores indicating lesser disorder.

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

The CaGI-I is single item questionnaire to assess the caregiver's impression of improvement in dyskinesia symptoms after initiating therapy. The scale is a caregiver-reported outcome that aims to evaluate all aspects of participants' health and determine if there has been an overall improvement or not in dyskinesia symptoms. The caregiver selected the 1 response from the response options that gave the most accurate description of change in dyskinesia symptoms of the participant they cared for from the beginning of the study: 1=very much improved (since the initiation of treatment); 2=much improved; 3=minimally improved; 4=no change from baseline (symptoms remain essentially unchanged); 5=minimally worse; 6=much worse; 7=very much worse (since the initiation of treatment).

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

CGI-I is a clinician-reported outcome that uses a 7-point Likert scale that allows the clinician to compare participant's condition at the visit to the baseline condition as follows: 1=very much improved since initiation of treatment (nearly all better; good level of functioning; minimal symptoms; represents a very substantial change); 2=much improved (notably better with significant reduction of symptoms; increase in the level of functioning but some symptoms remain); 3=minimally improved (slightly better with little or no clinically meaningful reduction of symptoms; represents very little change in basic clinical status, level of care, or functional capacity); 4=no change from baseline (symptoms remain unchanged); 5=minimally worse (slightly worse but may not be clinically meaningful); 6=much worse (clinically significant increase in symptoms and diminished functioning); 7=very much worse since the initiation of treatment (severe exacerbation of symptoms and loss of functioning).

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

The UHDRS-TMC is part of the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS) assessment and assesses the severity of chorea in the 7 body parts: face, mouth, trunk, and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). The central rating was done for all participants, based on the videos collected for the central rating of MD-CRS. The TMC score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 28 (marked/prolonged), with higher scores indicating the worse symptoms.

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

The UHDRS-TMD is part of the UHDRS-TMS assessment and assesses the severity of dystonia in the 5 body parts: trunk and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). The central rating was done for all participants, based on the videos collected for the central rating of MD-CRS. The TMD score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 20 (marked/prolonged), with higher scores indicating the worse symptoms.

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

The MD-CRS part I evaluates the impact of DCP on the activities of the participant and provides a general assessment of the movement disorder of motor function (7 items), oral/verbal function (3 items), self-care (3 items), and attention/alertness (2 items) on a scale of 0 (present) to 4 (absent). All items were scored by the investigational center physician. The total score was obtained by summing the individual items scores and ranges from 0 (marked/prolonged movement disorder) to 60 (absent of a movement disorder), with higher scores indicating lesser movement disorder.

Change From Baseline in the MD-CRS Part II Total Score (General Assessment, Physician Rated) at Week 15

The MD-CRS part II evaluates the severity of the movement disorder in a scale of 0 to 4 in 7 body regions, all areas in which dyskinesia can be seen in participants with CP. All items were scored by the investigational center physician. In rating the movement disorder of the 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. The 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.

Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Physician Rated) at Week 15

The MD-CRS Global Index is a global measure of the MD-CRS that consolidates the information from parts I and II using the method of weighted means of the 2 normalized indexes obtained from each part. The standardized/normalized score for each item of MD-CRS parts I and II with value X is calculated using the formula: Xst = X - Xmin divided by Xmax - Xmin, where Xmax is the maximum value for the score, and Xmin is the minimum value for the score, or 4 and 0 respectively. The normalized index for the scale, MD-CRS parts I or II, Index I or II, is calculated as the mean value of Xst. The MD-CRS Global Index is the weighted mean of the normalized indexes for centrally read MD-CRS parts I and II using the formula: Global index = n1 * index 1 + n2 * index 2 divided by n1 + n2, where n1 and n2 are the numbers of items in MD-CRS parts I and II respectively. The minimum score is 0 (better) and the maximum score is 1 (worse). The higher score indicates more severe movement disorder.

Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Centrally Read) at Week 15

Change From Baseline in UHDRS-TMS Score (Physician Rated) at Week 15

The UHDRS comprises a broad assessment of features associated with Huntington's disease (HD). It is a research tool that has been developed to provide a uniform assessment of the clinical features and course of HD. The Total Motor Score assessment of the UHDRS (UHDRS-TMS) comprises 15 items and assesses eye movements, speech, alternating hand movements, dystonia, chorea, and gait. The UHDRS-TMS was calculated as the sum of the 31 motor assessments; each of which ranged between 0 (absent) to 4 (worst). All items were scored by the investigational center physician. TMS score is a sum of individual scores ranging from 0 (normal motor function) to 124 (severely impaired motor function), with lower scores indicating better motor function.

Change From Baseline in UHDRS-TMC Score (Physician Rated) at Week 15

The UHDRS-TMC is part of the UHDRS-TMS assessment and assesses the severity of chorea in the 7 body parts: face, mouth, trunk, and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). All items were scored by the investigational center physician. The TMC score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 28 (marked/prolonged), with higher scores indicating the worse symptoms.

Change From Baseline in UHDRS-TMD Score (Physician Rated) at Week 15

The UHDRS-TMD is part of the UHDRS-TMS assessment and assesses the severity of dystonia in the 5 body parts: trunk and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). All items were scored by the investigational center physician. The TMD score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 20 (marked/prolonged), with higher scores indicating the worse symptoms.

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

The PEDI-CAT measures function in 4 domains: (1) Daily Activities; (2) Mobility; (3) Social/Cognitive, and (4) Responsibility. The content balanced version presents a balance of items from each of the Daily Activities domain's content areas (Getting Dressed, Keeping Clean, Home Tasks, and Eating and Mealtime). A total of approximately 30 items were administered. PEDI-CAT software utilizes Item Response Theory statistical models to estimate a child's abilities from a minimal number of the most relevant items or from a set number of items within each domain. The CAT program then displays the results: normative standard scores, scaled scores and SE. Scaled score is reported in this endpoint. Scaled scores are based on an estimate of the placement of an individual child along the hierarchical scale within each domain. PEDI-CAT scaled scores are currently on a 20 (lesser improvement) to 80 (more improvement) scale metric. Higher scores indicate greater improvement in functional skills.

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

The 35-item PedsQL 3.0 CP module encompasses 7 scales: Daily Activities (9 items); School Activities (4 items); Movement and Balance (5 items); Pain and Hurt (4 items); Fatigue (4 items); Eating Activities (5 items); and Speech and Communication (4 items). For children ages 6 and 7 years and 8 to 12 years, a child self-report and a parent proxy report are completed. For children ages 13 to 18 years, no parent proxy report is required. A 5-point response scale is utilized across child self-report and parent proxy report: 0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem. Items are reverse scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better quality of life (fewer problems). Total score was computed as the sum of 35 items divided by the number of items answered. Change from baseline scores can range from -100 to 100.

Patient Global Impression of Improvement (PGI-I) Scale Score (Global, Participant/Caregiver) at Week 15

The PGI-I is single item questionnaire to assess the participant's impression of improvement in dyskinesia symptoms after initiating therapy. The scale is a participant-reported outcome that aims to evaluate all aspects of participants' health and determine if there has been an overall improvement or not in dyskinesia symptoms. The participant selected the 1 response from the visual response options ("emojis") that gave the most accurate description of his/her state of health and overall status: 1=much improved (since the initiation of treatment); 2=somewhat improved; 3=no change; 4=somewhat worse; 5=much worse (since the initiation of treatment).

Change From Baseline in Clinical Global Impression of Severity (CGI-S) Scale Score (Global, Physician Rated) at Week 15

The CGI-S uses a 7-point Likert scale to assess dyskinesia severity as follows (with anchor points for choosing the most appropriate severity level caused by DCP): 1=normal (not at all ill, symptoms of disorder not present past 7 days); 2=borderline (subtle or suspected pathology); 3=mild (clearly established symptoms with minimal, if any, distress or difficulty in social and/or occupational function); 4=moderate (overt symptoms causing noticeable, but modest, functional impairment or distress; symptom level may warrant medication); 5=marked (intrusive symptoms that distinctly impair social/occupational function or cause intrusive levels of distress); 6=severe (disruptive symptoms, behavior and function are frequently influenced by symptoms, may require assistance from others); 7=extreme (symptoms drastically interferes in many life functions; may be hospitalized).

Number of Participants With CaGI-I Response

CaGI-I response was defined as participants who were described by the caregiver as "Much Improved" or "Very Much Improved" in the CaGI-I score. The CaGI-I is single item questionnaire to assess the caregiver's impression of improvement in dyskinesia symptoms after initiating therapy. The scale is a caregiver-reported outcome that aims to evaluate all aspects of participants' health and determine if there has been an overall improvement or not in dyskinesia symptoms. The caregiver selected the 1 response from the response options that gave the most accurate description of change in dyskinesia symptoms of the participant they cared for from the beginning of the study: 1=very much improved (since the initiation of treatment); 2=much improved; 3=minimally improved; 4=no change from baseline (symptoms remain essentially unchanged); 5=minimally worse; 6=much worse; 7=very much worse (since the initiation of treatment).

Number of Participants With CGI-I Response

CGI-I response was defined as participants who were described as "Much Improved" or "Very Much Improved" in the CGI-I score. CGI-I is a clinician-reported outcome that uses a 7-point Likert scale that allows the clinician to compare participant's condition at the visit to the baseline condition as follows: 1=very much improved since initiation of treatment (nearly all better; good level of functioning; minimal symptoms); 2=much improved (notably better with significant reduction of symptoms; increase in the level of functioning but some symptoms remain); 3=minimally improved (slightly better with little or no clinically meaningful reduction of symptoms); 4=no change from baseline (symptoms remain unchanged); 5=minimally worse (slightly worse but may not be clinically meaningful); 6=much worse (clinically significant increase in symptoms and diminished functioning); 7=very much worse since the initiation of treatment (severe exacerbation of symptoms and loss of functioning).

Number of Participants With CGI-S Response

CGI-S response was defined as participants who had a reduction of ≥1 point in the CGI-S score. The CGI-S uses a 7-point Likert scale to assess dyskinesia severity as follows (with anchor points for choosing the most appropriate severity level caused by DCP): 1=normal (not at all ill, symptoms of disorder not present past 7 days); 2=borderline (subtle or suspected pathology); 3=mild (clearly established symptoms with minimal, if any, distress or difficulty in social and/or occupational function); 4=moderate (overt symptoms causing noticeable, but modest, functional impairment or distress; symptom level may warrant medication); 5=marked (intrusive symptoms that distinctly impair social/occupational function or cause intrusive levels of distress); 6=severe (disruptive symptoms, behavior and function are frequently influenced by symptoms, may require assistance from others); 7=extreme (symptoms drastically interferes in many life functions; may be hospitalized).

Number of Participants With PGI-I Response

PGI-I response was defined as participants who were described as "Much Improved" or "Somewhat Improved" in the PGI-I score. The PGI-I is single item questionnaire to assess the participant's impression of improvement in dyskinesia symptoms after initiating therapy. The scale is a participant-reported outcome that aims to evaluate all aspects of participants' health and determine if there has been an overall improvement or not in dyskinesia symptoms. The participant selected the 1 response from the visual response options ("emojis") that gave the most accurate description of his/her state of health and overall status: 1=much improved (since the initiation of treatment); 2=somewhat improved; 3=no change; 4=somewhat worse; 5=much worse (since the initiation of treatment).

Number of Participants With Adverse Events (AEs)

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'.

Number of Participants With Shift From Baseline to Week 15 in Electrocardiogram (ECG) Findings

The number of participants with a difference (shift) from baseline in any of the following ECG parameters is reported by group: Heart rate, PR interval, QRS interval, RR interval, QT interval, and QT interval corrected using the Fridericia formula (QTcF). Shifts represented as Baseline - Week 15 value (last observed postbaseline value).

Change From Baseline in Child Behavior Checklist (CBCL) Competence Total Score at Week 15

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), was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior.

Change From Baseline in Child Behavior Checklist (CBCL) Syndrome Total Score at Week 15

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), was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior.

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale I Total Score at Week 15

The ESRS subscale I is a 7-item subjective questionnaire to evaluate parkinsonism, akathisia, dystonia and dyskinesia. The ESRS I is scored on 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.

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale II Total Score at Week 15

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 which from ranges from 0 (absent) to 102 (severe). Higher scores indicate greater severity of disorder.

Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 15

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 which ranges from 0 (never) to 24 (high chance of falling asleep). Higher scores indicate high chances of falling asleep.

Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Outcomes (Suicidal Ideation and Suicidal Behavior) at Week 15

Participants were placed into categories for suicidal ideation and suicidal behavior based on their responses to various questions. For suicidal ideation, 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; and Specific plan and intent. For suicidal behavior, following categories were used: None; Preparatory acts or behavior; Aborted attempt; Interrupted attempt; Actual attempt; and Suicide. Number of participants with suicidal ideation and/or suicidal behavior at Week 15 are reported.

Full Information

NCT ID

NCT03813238

First Posted

January 22, 2019

Last Updated

August 14, 2023

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03813238

Brief Title

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

Acronym

RECLAIM-DCP

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

August 6, 2019 (Actual)

Primary Completion Date

July 5, 2022 (Actual)

Study Completion Date

July 21, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cerebral Palsy, Dyskinetic

Keywords

DCP

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

63 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TEV-50717

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Matching placebo

Intervention Type

Drug

Intervention Name(s)

TEV-50717

Other Intervention Name(s)

Deutetrabenazine, (previously SD-809)

Intervention Description

Dosage ranging from 6 mg to 48 mg.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Dosage ranging from 6 mg to 48 mg.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline, Week 15

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline, Week 15

Title

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

Description

Time Frame

Week 15

Title

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

Description

Time Frame

Week 15

Title

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

Description

Time Frame

Baseline, Week 15

Title

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

Description

Time Frame

Baseline, Week 15

Title

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

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in the MD-CRS Part II Total Score (General Assessment, Physician Rated) at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Physician Rated) at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Centrally Read) at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in UHDRS-TMS Score (Physician Rated) at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in UHDRS-TMC Score (Physician Rated) at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in UHDRS-TMD Score (Physician Rated) at Week 15

Description

The UHDRS-TMD is part of the UHDRS-TMS assessment and assesses the severity of dystonia in the 5 body parts: trunk and the 4 extremities (right and left upper extremities, right and left lower extremities). Each part was rated from 0 (absent) to 4 (prolonged). All items were scored by the investigational center physician. The TMD score was obtained by adding up each of the separate scores and ranged from 0 (absent) to 20 (marked/prolonged), with higher scores indicating the worse symptoms.

Time Frame

Baseline, Week 15

Title

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

Description

Time Frame

Baseline, Week 15

Title

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

Description

Time Frame

Baseline, Week 15

Title

Patient Global Impression of Improvement (PGI-I) Scale Score (Global, Participant/Caregiver) at Week 15

Description

Time Frame

Week 15

Title

Change From Baseline in Clinical Global Impression of Severity (CGI-S) Scale Score (Global, Physician Rated) at Week 15

Description

Time Frame

Baseline, Week 15

Title

Number of Participants With CaGI-I Response

Description

Time Frame

Week 15

Title

Number of Participants With CGI-I Response

Description

Time Frame

Week 15

Title

Number of Participants With CGI-S Response

Description

Time Frame

Week 15

Title

Number of Participants With PGI-I Response

Description

Time Frame

Week 15

Title

Number of Participants With Adverse Events (AEs)

Description

Time Frame

Baseline up to Week 17

Title

Number of Participants With Shift From Baseline to Week 15 in Electrocardiogram (ECG) Findings

Description

Time Frame

Baseline to Week 15

Title

Change From Baseline in Child Behavior Checklist (CBCL) Competence Total Score at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in Child Behavior Checklist (CBCL) Syndrome Total Score at Week 15

Description

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), was calculated by adding individual score of each domain. Higher scores indicate greater problems in child behavior.

Time Frame

Baseline, Week 15

Title

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale I Total Score at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale II Total Score at Week 15

Description

Time Frame

Baseline, Week 15

Title

Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 15

Description

Time Frame

Baseline, Week 15

Title

Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Outcomes (Suicidal Ideation and Suicidal Behavior) at Week 15

Description

Time Frame

Week 15

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Teva Medical Expert, MD

Organizational Affiliation

Teva Branded Pharmaceutical Products R&D, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Teva Investigational Site 14137

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35233

Country

United States

Facility Name

Teva Investigational Site 14224

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85016

Country

United States

Facility Name

Teva Investigational Site 14227

City

Loma Linda

State/Province

California

ZIP/Postal Code

92354

Country

United States

Facility Name

Teva Investigational Site 14295

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

Teva Investigational Site 14293

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Teva Investigational Site 14127

City

Miami

State/Province

Florida

ZIP/Postal Code

33155

Country

United States

Facility Name

Teva Investigational Site 14125

City

Tampa

State/Province

Florida

ZIP/Postal Code

33609

Country

United States

Facility Name

Teva Investigational Site 14136

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30318

Country

United States

Facility Name

Teva Investigational Site 14291

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30328

Country

United States

Facility Name

Teva Investigational Site 14130

City

Savannah

State/Province

Georgia

ZIP/Postal Code

31406

Country

United States

Facility Name

Teva Investigational Site 14290

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70118-5720

Country

United States

Facility Name

Teva Investigational Site 14226

City

Saint Paul

State/Province

Minnesota

ZIP/Postal Code

55101

Country

United States

Facility Name

Teva Investigational Site 14134

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68526

Country

United States

Facility Name

Teva Investigational Site 14122

City

Gibbsboro

State/Province

New Jersey

ZIP/Postal Code

08026

Country

United States

Facility Name

Teva Investigational Site 14297

City

New Brunswick

State/Province

New Jersey

ZIP/Postal Code

08901

Country

United States

Facility Name

Teva Investigational Site 14225

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Teva Investigational Site 14123

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

Teva Investigational Site 14348

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Teva Investigational Site 14299

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29414

Country

United States

Facility Name

Teva Investigational Site 14129

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Teva Investigational Site 14228

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Teva Investigational Site 14223

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

Facility Name

Teva Investigational Site 14135

City

Everett

State/Province

Washington

ZIP/Postal Code

98201

Country

United States

Facility Name

Teva Investigational Site 37100

City

Luxembourg City

ZIP/Postal Code

1210

Country

Belgium

Facility Name

Teva Investigational Site 37102

City

Woluwe-Saint-Lambert

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Teva Investigational Site 11165

City

Nepean

State/Province

Ontario

ZIP/Postal Code

K2G 1W2

Country

Canada

Facility Name

Teva Investigational Site 39058

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

Facility Name

Teva Investigational Site 80144

City

Jerusalem

ZIP/Postal Code

9103102

Country

Israel

Facility Name

Teva Investigational Site 80145

City

Safed

ZIP/Postal Code

13100

Country

Israel

Facility Name

Teva Investigational Site 80146

City

Tel-Aviv

ZIP/Postal Code

6423906

Country

Israel

Facility Name

Teva Investigational Site 80147

City

Zerifin

ZIP/Postal Code

70300

Country

Israel

Facility Name

Teva Investigational Site 30217

City

Firenze

ZIP/Postal Code

50139

Country

Italy

Facility Name

Teva Investigational Site 30214

City

Milan

ZIP/Postal Code

20133

Country

Italy

Facility Name

Teva Investigational Site 30213

City

Napoli

ZIP/Postal Code

80138 -

Country

Italy

Facility Name

Teva Investigational Site 30216

City

Pisa

ZIP/Postal Code

56018

Country

Italy

Facility Name

Teva Investigational Site 30215

City

Roma

ZIP/Postal Code

00168

Country

Italy

Facility Name

Teva Investigational Site 30212

City

Roma

ZIP/Postal Code

00185

Country

Italy

Facility Name

Teva Investigational Site 53434

City

Gdansk

ZIP/Postal Code

80-211

Country

Poland

Facility Name

Teva Investigational Site 53428

City

Gdansk

ZIP/Postal Code

80-389

Country

Poland

Facility Name

Teva Investigational Site 53427

City

Krakow

ZIP/Postal Code

30-539

Country

Poland

Facility Name

Teva Investigational Site 53431

City

Lublin

ZIP/Postal Code

20-828

Country

Poland

Facility Name

Teva Investigational Site 53432

City

Poznan

ZIP/Postal Code

60-693

Country

Poland

Facility Name

Teva Investigational Site 53433

City

Strzelin

ZIP/Postal Code

57100

Country

Poland

Facility Name

Teva Investigational Site 53430

City

Wiazowna

ZIP/Postal Code

05-462

Country

Poland

Facility Name

Teva Investigational Site 50477

City

Kazan

ZIP/Postal Code

420021

Country

Russian Federation

Facility Name

Teva Investigational Site 50475

City

Khabarovsk

ZIP/Postal Code

680013

Country

Russian Federation

Facility Name

Teva Investigational Site 50473

City

Moscow

ZIP/Postal Code

117513

Country

Russian Federation

Facility Name

Teva Investigational Site 50470

City

Moscow

ZIP/Postal Code

129110

Country

Russian Federation

Facility Name

Teva Investigational Site 50485

City

Nizhniy Novgorod

ZIP/Postal Code

603950

Country

Russian Federation

Facility Name

Teva Investigational Site 50468

City

Novosibirsk

ZIP/Postal Code

630091

Country

Russian Federation

Facility Name

Teva Investigational Site 50469

City

Smolensk

ZIP/Postal Code

214018

Country

Russian Federation

Facility Name

Teva Investigational Site 50478

City

Stavropol

ZIP/Postal Code

999999

Country

Russian Federation

Facility Name

Teva Investigational Site 50474

City

Tyumen

ZIP/Postal Code

625023

Country

Russian Federation

Facility Name

Teva Investigational Site 62054

City

Banska Bystrica

ZIP/Postal Code

974 04

Country

Slovakia

Facility Name

Teva Investigational Site 62053

City

Dubnica Nad Vahom

ZIP/Postal Code

01841

Country

Slovakia

Facility Name

Teva Investigational Site 31259

City

Cordoba

ZIP/Postal Code

14011

Country

Spain

Facility Name

Teva Investigational Site 31256

City

Granada

ZIP/Postal Code

18013

Country

Spain

Facility Name

Teva Investigational Site 31255

City

Madrid

ZIP/Postal Code

28009

Country

Spain

Facility Name

Teva Investigational Site 31257

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Teva Investigational Site 31258

City

Sevilla

ZIP/Postal Code

41015

Country

Spain

Facility Name

Teva Investigational Site 31254

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

Teva Investigational Site 58313

City

Dnipropetrovsk

ZIP/Postal Code

49027

Country

Ukraine

Facility Name

Teva Investigational Site 58312

City

Kharkiv

ZIP/Postal Code

61068

Country

Ukraine

Facility Name

Teva Investigational Site 58309

City

Kyiv

ZIP/Postal Code

04209

Country

Ukraine

Facility Name

Teva Investigational Site 58311

City

Odesa

ZIP/Postal Code

65012

Country

Ukraine

Facility Name

Teva Investigational Site 58310

City

Vinnytsya

ZIP/Postal Code

21037

Country

Ukraine

Facility Name

Teva Investigational Site 34246

City

Bristol

ZIP/Postal Code

BS2 8BJ

Country

United Kingdom

Facility Name

Teva Investigational Site 34245

City

Edinburgh

ZIP/Postal Code

EH9 1LF

Country

United Kingdom

Facility Name

Teva Investigational Site 34243

City

London

ZIP/Postal Code

SE1 7EH

Country

United Kingdom

Facility Name

Teva Investigational Site 34244

City

Sheffield

ZIP/Postal Code

S10 2TH

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.

Learn more about this trial

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

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

Cerebral Palsy, Dyskinetic

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial