BOTOX® Treatment in Pediatric Lower Limb Spasticity

Phase 3

Completed

• Conditions: Muscle Spasticity; Cerebral Palsy; Pediatrics
• Interventions: Biological: botulinum toxin Type A; Drug: Normal Saline (Placebo)

• Registration Number: NCT01603628
• Lead Sponsor: Allergan

Brief Summary

This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with lower limb spasticity.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-05-21
• Study First Submitted QC: 2012-05-21
• Study First Posted: 2012-05-22
• Study Start: 2012-09-11
• Primary Completion: 2017-06-28
• Study Completion: 2017-06-28
• Results First Submitted: 2018-06-12
• Status Verified: 2018-07
• Results First Submitted QC: 2018-07-16
• Last Update Submitted: 2018-07-16
• Results First Posted: 2018-08-14
• Last Update Posted: 2018-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 384

Inclusion Criteria

• Minimum weight of 10 kg/22 lb
• Cerebral palsy with dynamic muscle contracture /spasticity of the ankle

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Exclusion Criteria

• Muscular dystrophy, myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or mitochondrial disease
• Uncontrolled epilepsy
• Botulinum Toxin therapy of any serotype for any condition within the last 6 months
• History of surgical intervention of the lower study leg or planned surgery of any limb during the study
• Previous casting of the study limb for spasticity within 6 months or with a dynamic splint within 3 months, or planned casting or dynamic splinting for spasticity of the study limb or affected upper limb during the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BOTOX® 8 U/kg	botulinum toxin Type A	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)	Normal Saline (Placebo)	Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1. Participants received weekly PT.
BOTOX® 4 U/kg	botulinum toxin Type A	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).

Primary Outcome Measures

Name	Time	Method
Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6	Baseline (Day 1) to 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.
Average Clinical Global Impression (CGI) of Overall Change by Physician at Weeks 4 and 6	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.

Secondary Outcome Measures

Name	Time	Method
Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale	Weeks 8 and 12	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.
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)	Baseline (Day 1) to Weeks 2, 4, 6, 8 and 12	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.

Trial Locations

Locations (53)

Harrison Clinical Management; 🇺🇸 Pomona, California, United States

AMS Neurology; 🇺🇸 Pasadena, California, United States

Children's Healthcare of Atlanta Children's Rehabilitation Associates; 🇺🇸 Atlanta, Georgia, United States

The Children's Mercy Hospital & Clinics; 🇺🇸 Kansas City, Missouri, United States

NYU Hospital for Joint Diseases; 🇺🇸 New York, New York, United States

OnSite Clinical Solutions, LLC; 🇺🇸 Charlotte, North Carolina, United States

Columbia University Medical Center Dept. of Rehab. & Regenerative Medicine; 🇺🇸 New York, New York, United States

PMG Research of Charlotte, LLC; 🇺🇸 Charlotte, North Carolina, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Marshfield Clinic; 🇺🇸 Marshfield, Wisconsin, United States

Daegu Fatima Hospital; 🇰🇷 Daegu, Korea, Republic of

Philippine Orthopedic Center; 🇵🇭 Quezon City, Philippines

Specjal. Gabinet Neurologiczny; 🇵🇱 Krakow, Poland

INTERMED, Lublin; 🇵🇱 Lublin, Poland

Szpital Wojewódzki Nr 2; 🇵🇱 Rzeszów, Poland

Childrens Republic Hospital; 🇷🇺 Kazan, Russian Federation

NZOZ Mazowieckie Centrum; 🇵🇱 Warsaw, Poland

Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region; 🇷🇺 Tyumen, Russian Federation

Smolensk Regional Hospital- Regional Budget State Healthcare institution; 🇷🇺 Smolensk, Russian Federation

Srinagarind Hospital, Khon Kaen University; 🇹🇭 Khon Kaen, Thailand

Kocaeli Üniversitesi; 🇹🇷 Kocaeli, Turkey

Ankara Diskapi Yildrim Beyazit; 🇹🇷 Ankara, Turkey

Selçuk Üniversitesi; 🇹🇷 Konya, Turkey

Children's Hospital Colorado Dept. of PM&R; 🇺🇸 Aurora, Colorado, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Rehab Institute of Chicago; 🇺🇸 Chicago, Illinois, United States

Baylor College of Medicine Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Road Runner Research; 🇺🇸 San Antonio, Texas, United States

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Semmelweis Egyetem- Ortopédiai Klinika; 🇭🇺 Budapest, Hungary

National Health Insurance Service Ilsan Hospital; 🇰🇷 Gyeonggi-do, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

St. Luke's Medical Center-Quezon City; 🇵🇭 Quezon City, Philippines

Philippine Children's Medical Center; 🇵🇭 Quezon City, Philippines

Uni Centrum Kliniczne; 🇵🇱 Gdansk, Poland

Neuro - Dzieci I Mlodziezy Aga; 🇵🇱 Warsaw, Poland

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Pediatric Neurology, PA; 🇺🇸 Orlando, Florida, United States

Associated Neurologists of Southern CT, P.C.; 🇺🇸 Fairfield, Connecticut, United States

Uniwersytecki Dzieciecy Szpita; 🇵🇱 Białystok, Poland

Centrum Rehabilitacji Krok po Kroku; 🇵🇱 Gdansk, Poland

New England Center for Clinical Research; 🇺🇸 Stamford, Connecticut, United States

Debrecen University Clinical Center, Orthopedic Clinic; 🇭🇺 Debrecen, Hungary

Istituto IRCCS G. Gaslini; 🇮🇹 Genoa, Italy

CRH ŻAGIEL MED, Lublin; 🇵🇱 Lublin, Poland

Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University; 🇹🇭 Chiang Mai, Thailand

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Clinical Research Center of New Jersey; 🇺🇸 Voorhees, New Jersey, United States

Axcess Medical Research, LLC; 🇺🇸 Loxahatchee Groves, Florida, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

NW FL Clinical Research Group, LLC; 🇺🇸 Gulf Breeze, Florida, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States