BOTOX® Treatment in Pediatric Upper Limb Spasticity

BOTOX® Treatment in Pediatric Upper Limb Spasticity: Double-blind Study

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

Study Overview

• Status: Completed
• Conditions: Stroke; Cerebral Palsy; Muscle Spasticity; Pediatrics
• Intervention / Treatment: Biological: botulinum toxin Type A; Drug: Normal Saline (Placebo)

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 1R8
      • Holland Bloorview Kids Rehab
• Hungary
  • Debrecen, Hungary, 4032
    • Debrecen University Clinical Center, Orthopedic Clinic
• Korea, Republic of
  • Daegu, Korea, Republic of, 41199
    • Daegu Fatima Hospital
  • Goyang-si, Korea, Republic of, 10444
    • National Health Insurance Service Ilsan Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Philippines
  • Cavite
    • Dasmarinas, Cavite, Philippines, 4114
      • De La Salle University Medical Center
  • Quezon City
    • Bagong Pag-asa, Quezon City, Philippines, 1104
      • Philippine Children's Medical Center
• Poland
  • Gdansk, Poland, 80-219
    • Uni Centrum Kliniczne
  • Krakow, Poland, 30-359
    • Specjal. Gabinet Neurologiczny
  • Lodz, Poland, 93-271
    • Centrum Medyczne "POMOC"
  • Lublin, Poland, 20-058
    • INTERMED, Lublin
  • Lublin, Poland, 20-601
    • CRH ŻAGIEL MED, Lublin
  • Warsaw, Poland, 02-315
    • Neuro - Dzieci I Mlodziezy Aga
  • Warsaw, Poland, 05-462
    • NZOZ Mazowieckie Centrum
• Russian Federation
  • Kazan, Russian Federation, 420138
    • Childrens Republic Hospital
  • Smolensk, Russian Federation, 214018
    • Smolensk Regional Hospital- Regional Budget State Healthcare institution
  • Tyumen, Russian Federation, 625039
    • Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital, Mahidol University
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital, Khon Kaen University
• Turkey
  • Ankara, Turkey, 6110
    • Ankara Diskapi Yildrim Beyazit
  • Kocaeli, Turkey, 41380
    • Kocaeli Üniversitesi
• United States
  • California
    • Pasadena, California, United States, 91106
      • AMS Neurology
    • Pomona, California, United States, 91766
      • Harrison Clinical Management
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado Dept. of PM&R
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern CT, P.C.
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • NW FL Clinical Research Group, LLC
    • Loxahatchee Groves, Florida, United States, 33470
      • Axcess Medical Research, LLC
    • Orlando, Florida, United States, 32891
      • Pediatric Neurology, PA
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta Children's Rehabilitation Associates
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Gillette Children's Specialty Healthcare
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Clinical Research Center Of New Jersey
  • New York
    • New York, New York, United States, 10003
      • NYU Hospital for Joint Diseases
    • New York, New York, United States, 10032
      • Columbia University Medical Center Dept. of Rehab. & Regenerative Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Onsite Clinical Solutions, LLC
    • Charlotte, North Carolina, United States, 28203
      • PMG Research if Charlotte, LLC
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Texas Children's Hospital
    • San Antonio, Texas, United States, 78258
      • Road Runner Research
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Minimum weight of 10 kg/22 lb
• Upper limb spasticity due to cerebral palsy or stroke

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
• Previous surgical treatment of the study limb (except tendon lengthening), or planned surgery of the study 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 lower limb during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BOTOX® 3 U/kg; Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 units (U) per kilogram (kg) of body weight (3 U/kg) into specified muscles of the upper limb on Day 1. Participants received weekly occupational therapy (OT).	Biological: botulinum toxin Type A; Intramuscular injections of botulinum toxin Type A into specified muscles of the upper limb on Day 1.; Other Names: BOTOX®; onabotulinumtoxinA
Experimental: BOTOX® 6 U/kg; Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 6 U per kg of body weight (6 U/kg) into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Biological: botulinum toxin Type A; Intramuscular injections of botulinum toxin Type A into specified muscles of the upper limb on Day 1.; Other Names: BOTOX®; onabotulinumtoxinA
Placebo Comparator: Placebo; Participants received intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1. Participants received weekly OT.	Drug: Normal Saline (Placebo); Intramuscular injections of normal saline (placebo) into specified muscles of the upper limb on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Score of the Principal Muscle Group 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 MMRM model was used for analysis.	Weeks 4 and 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change From Baseline in MAS-B Score of the Finger Flexor Muscle Group at Weeks 4 and 6	The MAS-B was used to evaluate spasticity based on grading the resistance encountered in the finger flexor muscle group 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. An Analysis of Covariance (ANCOVA) model was used for analysis. A negative change from Baseline indicates improvement.	Baseline (Day 1) to Weeks 4 and 6
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 ANCOVA model was used for analysis.	Week 8 and 12
Change From Baseline in Severity of Spasticity of the Principal Muscle Group (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 a fast velocity passive stretch determining the dynamic component of the muscle contracture for the joint. At each visit, 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 slow (R2) and fast (R1) range of motion and respective change from baseline to each posttreatment office visit on the MTS was derived.	Baseline (Day 1) to Week 6

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2012
• Primary Completion (Actual): June 29, 2017
• Study Completion (Actual): July 6, 2017

Study Registration Dates

• First Submitted: May 21, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimate): May 22, 2012

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Cerebral Palsy; Muscle Spasticity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 191622-101; 2012-000062-38 (EudraCT Number)