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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000042-35 | EudraCT Number |
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This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with lower limb spasticity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BOTOX® 4 U/kg | Experimental | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT). |
|
| BOTOX® 8 U/kg | Experimental | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. |
|
| Normal Saline (Placebo) | Placebo Comparator | Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1. Participants received weekly PT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| botulinum toxin Type A | Biological | Participants received intramuscular injections of botulinum toxin Type A into specified muscles of the lower limb on Day 1. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6 | The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the principal muscle group (elbow and wrist) by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. A negative change from Baseline indicates improvement. | Baseline (Day 1) to Weeks 4 and 6 |
| Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6 | The CGI of overall change (improvement or worsening) was assessed by the physician considering the participant's clinical condition and severity of side effects using a 9-point scale where: -4=very marked worsening to +4=very marked improvement. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. | Weeks 4 and 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Two functional goals, one active and one passive, were selected by the participant and family in consultation with the physician investigator and/or treating physical therapist relative to the lower limb impairment due to spasticity. The physician assessed the achievement of the goals using a 6-point scale: where -3=worse than start to +2=much more than expected: improvements clearly exceed the defined therapeutic goal. An Analysis of Covariance (ANCOVA) model was used for analysis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rozalina Dimitrova | Allergan | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AMS Neurology | Pasadena | California | 91106 | United States | ||
| Harrison Clinical Management |
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| Label | URL |
|---|---|
| Additional information on study locations near you may be found at AllerganClinicalTrials.com. For any study not on AllerganClinicalTrials.com, please contact IR-CTRegistration@Allergan.com for assistance. | View source |
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Pediatric participants with lower limb spasticity were randomized 1:1:1 to one of three treatment groups: BOTOX® 4 or 8 U/kg (unit per kilogram) or placebo.
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| ID | Title | Description |
|---|---|---|
| FG000 | BOTOX® 8 U/kg | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 units (U) per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT). |
| FG001 | BOTOX® 4 U/kg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 16, 2017 | Jun 12, 2018 |
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|
| Normal Saline (Placebo) | Drug | Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1. |
|
| Weeks 8 and 12 |
| Change From Baseline in Severity of Spasticity of the Ankle With Knee Extended and Knee Flexed (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | The MTS measured the difference between slow and fast range of motion (R2-R1) and respective change from baseline to each posttreatment office visit. The MTS of the ankle was used to determine the passive range of movement at different movement velocities, V1 (as slow as possible) and V3 (as fast as possible) with the relative difference between a slow and fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. The investigator measured 2 joint angles by goniometer: the R1 angle which is the angle of catch after a fast velocity (V3) stretch and the R2 angle defined as the passive joint range of movement following a slow velocity (V1) stretch. The R2-R1 value indicated the level of the dynamic component of spasticity in the joint. The difference between R2 and R1 range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived. An Analysis of Covariance (ANCOVA) model was used for analysis. | Baseline (Day 1) to Weeks 2, 4, 6, 8 and 12 |
| Pomona |
| California |
| 91767 |
| United States |
| Children's Hospital Colorado Dept. of PM&R | Aurora | Colorado | 80045 | United States |
| Associated Neurologists of Southern CT, P.C. | Fairfield | Connecticut | 06824 | United States |
| New England Center for Clinical Research | Stamford | Connecticut | 06905 | United States |
| NW FL Clinical Research Group, LLC | Gulf Breeze | Florida | 32561 | United States |
| Axcess Medical Research, LLC | Loxahatchee Groves | Florida | 33470 | United States |
| Pediatric Neurology, PA | Orlando | Florida | 32819 | United States |
| Children's Healthcare of Atlanta Children's Rehabilitation Associates | Atlanta | Georgia | 30342 | United States |
| Rehab Institute of Chicago | Chicago | Illinois | 60611 | United States |
| The Children's Mercy Hospital & Clinics | Kansas City | Missouri | 64108 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Clinical Research Center of New Jersey | Voorhees Township | New Jersey | 08043 | United States |
| NYU Hospital for Joint Diseases | New York | New York | 10003 | United States |
| Columbia University Medical Center Dept. of Rehab. & Regenerative Medicine | New York | New York | 10032 | United States |
| OnSite Clinical Solutions, LLC | Charlotte | North Carolina | 28203 | United States |
| PMG Research of Charlotte, LLC | Charlotte | North Carolina | 28203 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75235 | United States |
| Baylor College of Medicine Texas Children's Hospital | Houston | Texas | 77030 | United States |
| Road Runner Research | San Antonio | Texas | 78258 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Marshfield Clinic | Marshfield | Wisconsin | 54449 | United States |
| Semmelweis Egyetem- Ortopédiai Klinika | Budapest | 1113 | Hungary |
| Debrecen University Clinical Center, Orthopedic Clinic | Debrecen | 4032 | Hungary |
| Istituto IRCCS G. Gaslini | Genoa | 16148 | Italy |
| Philippine Orthopedic Center | Quezon City | 1100 | Philippines |
| St. Luke's Medical Center-Quezon City | Quezon City | 1102 | Philippines |
| Philippine Children's Medical Center | Quezon City | 1104 | Philippines |
| Uniwersytecki Dzieciecy Szpita | Bialystok | 15-274 | Poland |
| Uni Centrum Kliniczne | Gdansk | 80-219 | Poland |
| Centrum Rehabilitacji Krok po Kroku | Gdansk | 80-389 | Poland |
| Specjal. Gabinet Neurologiczny | Krakow | 30-359 | Poland |
| INTERMED, Lublin | Lublin | 20-058 | Poland |
| CRH ŻAGIEL MED, Lublin | Lublin | 20-601 | Poland |
| Szpital Wojewódzki Nr 2 | Rzeszów | 35-301 | Poland |
| Neuro - Dzieci I Mlodziezy Aga | Warsaw | 02-315 | Poland |
| NZOZ Mazowieckie Centrum | Warsaw | 05-462 | Poland |
| Childrens Republic Hospital | Kazan' | 420138 | Russia |
| Smolensk Regional Hospital- Regional Budget State Healthcare institution | Smolensk | 214018 | Russia |
| Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region | Tyumen | 625039 | Russia |
| Daegu Fatima Hospital | Daegu | 41199 | South Korea |
| National Health Insurance Service Ilsan Hospital | Gyeonggi-do | 10444 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| Severance Hospital, Yonsei University Health System | Seoul | 120-752 | South Korea |
| Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University | Chiang Mai | 50200 | Thailand |
| Srinagarind Hospital, Khon Kaen University | Khon Kaen | 40002 | Thailand |
| Ankara Diskapi Yildrim Beyazit | Ankara | 6110 | Turkey (Türkiye) |
| Kocaeli Üniversitesi | Kocaeli | 41380 | Turkey (Türkiye) |
| Selçuk Üniversitesi | Konya | 42250 | Turkey (Türkiye) |
Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. |
| FG002 | Placebo | Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT. |
| Safety Population: Received Treatment |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
All randomized participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | BOTOX® 8 U/kg | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT). |
| BG001 | BOTOX® 4 U/kg | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. |
| BG002 | Placebo | Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||
| Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score with Knee Extended | The MAS-B evaluates spasticity, grading the resistance encountered in the principal muscle group (elbow and wrist) by passively moving a limb through its range of motion at a specified velocity. The resistance encountered to passive stretch was graded on a 6-point scale: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. | 2 participants in the Placebo arm are not included in the analysis. | Mean | Standard Deviation | score on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6 | The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the principal muscle group (elbow and wrist) by means of passively moving a limb through its range of motion at a study specified velocity. The resistance encountered to passive stretch was graded using a 6-point scale where: 0=no increase in muscle tone (best) to 4=affected part(s) rigid in flexion or extension (worst). For analysis purposes, the MAS-B was recoded as follows: 0=1, 1=1, 1+=2, 2=3, 3=4, 4=5. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. A negative change from Baseline indicates improvement. | Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Day 1) to Weeks 4 and 6 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6 | The CGI of overall change (improvement or worsening) was assessed by the physician considering the participant's clinical condition and severity of side effects using a 9-point scale where: -4=very marked worsening to +4=very marked improvement. The scores at Weeks 4 and 6 were averaged. A Mixed Model Repeated Measures (MMRM) model was used for analysis. | Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis. | Posted | Least Squares Mean | Standard Error | score on a scale | Weeks 4 and 6 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale | Two functional goals, one active and one passive, were selected by the participant and family in consultation with the physician investigator and/or treating physical therapist relative to the lower limb impairment due to spasticity. The physician assessed the achievement of the goals using a 6-point scale: where -3=worse than start to +2=much more than expected: improvements clearly exceed the defined therapeutic goal. An Analysis of Covariance (ANCOVA) model was used for analysis. | Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis at the given time-point. | Posted | Least Squares Mean | Standard Error | score on a scale | Weeks 8 and 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Severity of Spasticity of the Ankle With Knee Extended and Knee Flexed (R2-R1) Calculated Using the Modified Tardieu Scale (MTS) | The MTS measured the difference between slow and fast range of motion (R2-R1) and respective change from baseline to each posttreatment office visit. The MTS of the ankle was used to determine the passive range of movement at different movement velocities, V1 (as slow as possible) and V3 (as fast as possible) with the relative difference between a slow and fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. The investigator measured 2 joint angles by goniometer: the R1 angle which is the angle of catch after a fast velocity (V3) stretch and the R2 angle defined as the passive joint range of movement following a slow velocity (V1) stretch. The R2-R1 value indicated the level of the dynamic component of spasticity in the joint. The difference between R2 and R1 range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived. An Analysis of Covariance (ANCOVA) model was used for analysis. | Participants from the mITT population, all randomized participants with a valid MAS-B baseline ankle score with knee extended and at least one post-baseline measurement at Weeks 2, 4, or 6 for the MAS-B of the ankle score with knee extended and the CGI by physician, with data available for analysis at the given time-point. | Posted | Least Squares Mean | Standard Error | degrees | Baseline (Day 1) to Weeks 2, 4, 6, 8 and 12 |
|
Baseline (Day 1) to the end of study (Week 12)
The Safety Population, all treated participants based on the treatment received, was used to determine the number of participants at risk for Serious Adverse Events and Adverse Events.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BOTOX® 8 U/kg | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 8 U per kg of body weight (8 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly physical therapy (PT). | 0 | 128 | 0 | 128 | 24 | 128 |
| EG001 | BOTOX® 4 U/kg | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. | 0 | 126 | 3 | 126 | 26 | 126 |
| EG002 | Placebo | Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT. | 0 | 128 | 4 | 128 | 35 | 128 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Extrasystoles | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastoeneteritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Radicular Pain | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area Head | Allergan | 714-246-4500 | clinicaltrials@allergan.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Jul 25, 2016 | Jun 12, 2018 | Prot_001.pdf |
| ID | Term |
|---|---|
| D009128 | Muscle Spasticity |
| D002547 | Cerebral Palsy |
| ID | Term |
|---|---|
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009122 | Muscle Hypertonia |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001925 | Brain Damage, Chronic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
|
|
|
| Black |
|
|
| Asian |
|
|
| Hispanic |
|
|
| Other Not Specified |
|
|
|
| Mixed Model Repeated Measures |
| 0.033 |
MMRM including baseline MAS-B ankle score (knee extended) as a covariate and factors of age, treatment, visit, treatment-by-visit interaction, study center and previous botulinum toxin exposure where age is represented by stratification categories. |
| LS Mean Difference |
| -0.21 |
| 2-Sided |
| 95 |
| -0.405 |
| -0.018 |
| Superiority |
| Placebo |
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT. |
|
|
|
| OG002 | Placebo | Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT. |
|
|
|
| OG001 | BOTOX® 4 U/kg | Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 U per kg of body weight (4 U/kg) into specified muscles of the lower limb on Day 1. Participants received weekly PT. |
| OG002 | Placebo | Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb. Participants received weekly PT. |
|
|
|