PediatricsPhase 3NCT01603628
BOTOX® Treatment in Pediatric Lower Limb Spasticity
A Phase 3 study testing botulinum toxin Type A in people with Pediatrics and Muscle Spasticity, run by Allergan at 53 sites in 9 countries.
Trial summary
This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with lower limb spasticity. Read more about this study
- Who is it for?
- Ages 2 to 16 years
- Conditions the study is for
- Pediatrics, Muscle Spasticity, Cerebral Palsy
- What is being tested?
- botulinum toxin Type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 384 participants
- Where
- 53 sitesin 9 countries
- Study dates
- 11 Sep 2012to 28 Jun 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Minimum weight of 10 kg/22 lb
- Cerebral palsy with dynamic muscle contracture /spasticity of the ankle
Who cannot join
- 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
Trial locations and contacts
53 sites in 9 countries.
53 sites in 9 countries
United States24 sites
Children's Healthcare of Atlanta Children's Rehabilitation Associates
Atlanta, Georgia, 30342
Children's Hospital Colorado Dept. of PM&R
Aurora, Colorado, 80045
OnSite Clinical Solutions, LLC
Charlotte, North Carolina, 28203
PMG Research of Charlotte, LLC
Charlotte, North Carolina, 28203
Rehab Institute of Chicago
Chicago, Illinois, 60611
University of Texas Southwestern Medical Center
Dallas, Texas, 75235
Associated Neurologists of Southern CT, P.C.
Fairfield, Connecticut, 06824
NW FL Clinical Research Group, LLC
Gulf Breeze, Florida, 32561
Baylor College of Medicine Texas Children's Hospital
Houston, Texas, 77030
The Children's Mercy Hospital & Clinics
Kansas City, Missouri, 64108
Axcess Medical Research, LLC
Loxahatchee Groves, Florida, 33470
Marshfield Clinic
Marshfield, Wisconsin, 54449
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
NYU Hospital for Joint Diseases
New York, New York, 10003
Columbia University Medical Center Dept. of Rehab. & Regenerative Medicine
New York, New York, 10032
Pediatric Neurology, PA
Orlando, Florida, 32819
AMS Neurology
Pasadena, California, 91106
Harrison Clinical Management
Pomona, California, 91767
Rhode Island Hospital
Providence, Rhode Island, 02903
Road Runner Research
San Antonio, Texas, 78258
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
New England Center for Clinical Research
Stamford, Connecticut, 06905
Clinical Research Center of New Jersey
Voorhees Township, New Jersey, 08043
Poland9 sites
Uniwersytecki Dzieciecy Szpita
Bialystok, 15-274
Uni Centrum Kliniczne
Gdansk, 80-219
Centrum Rehabilitacji Krok po Kroku
Gdansk, 80-389
Specjal. Gabinet Neurologiczny
Krakow, 30-359
INTERMED, Lublin
Lublin, 20-058
CRH ŻAGIEL MED, Lublin
Lublin, 20-601
Szpital Wojewódzki Nr 2
Rzeszów, 35-301
Neuro - Dzieci I Mlodziezy Aga
Warsaw, 02-315
NZOZ Mazowieckie Centrum
Warsaw, 05-462
South Korea6 sites
Daegu Fatima Hospital
Daegu, 41199
National Health Insurance Service Ilsan Hospital
Gyeonggi-do, 10444
Seoul National University Hospital
Seoul, 03080
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Severance Hospital, Yonsei University Health System
Seoul, 120-752
Philippines3 sites
Philippine Orthopedic Center
Quezon City, 1100
St. Luke's Medical Center-Quezon City
Quezon City, 1102
Philippine Children's Medical Center
Quezon City, 1104
Russia3 sites
Childrens Republic Hospital
Kazan', 420138
Smolensk Regional Hospital- Regional Budget State Healthcare institution
Smolensk, 214018
Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region
Tyumen, 625039
Turkey (Türkiye)3 sites
Ankara Diskapi Yildrim Beyazit
Ankara, 6110
Kocaeli Üniversitesi
Kocaeli, 41380
Selçuk Üniversitesi
Konya, 42250
Hungary2 sites
Semmelweis Egyetem- Ortopédiai Klinika
Budapest, 1113
Debrecen University Clinical Center, Orthopedic Clinic
Debrecen, 4032
Thailand2 sites
Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University
Chiang Mai, 50200
Srinagarind Hospital, Khon Kaen University
Khon Kaen, 40002
About this study
Official title: BOTOX® Treatment in Pediatric Lower Limb Spasticity: Double-blind Study
This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with lower limb spasticity.
- Conditions
- Pediatrics, Muscle Spasticity, Cerebral Palsy
- Being tested
- botulinum toxin Type A, Normal Saline (Placebo)
- Medical subject headings
- Muscle Spasticity, Cerebral Palsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
botulinum toxin Type ABiological
Also called BOTOX®
Participants received intramuscular injections of botulinum toxin Type A into specified muscles of the lower limb on Day 1.
Normal Saline (Placebo)Drug
Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Biological: botulinum toxin Type A |
| 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. Receives: Biological: botulinum toxin Type A |
| 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. Receives: Drug: Normal Saline (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Weeks 4 and 6
Secondary outcomes (2)
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.
Measured: 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.
Measured: Baseline (Day 1) to Weeks 2, 4, 6, 8 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2012 (estimated)
- Study start11 Sep 2012
- Primary completion28 Jun 2017
- Study completion28 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PediatricsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 384 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allergan
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rozalina Dimitrova, Study director, Allergan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01603628
- Sponsor's protocol ID
- 191622-111
- Other IDs
- 2012-000042-35
- Status last verified
- Jul 2018
- First submitted
- 21 May 2012
- Last updated
- 14 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BOTOX® Treatment in Pediatric Lower Limb Spasticity: Double-blind Study
- ClinicalTrials.gov ID
- NCT01603628
- Acronym / sponsor ID
- 191622-111
- Conditions
- Pediatrics, Muscle Spasticity, Cerebral Palsy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 384 participants (actual)
- Lead sponsor
- AllerganIndustry (pharma, biotech, devices)
- Study start
- 11 Sep 2012 (actual)
- Primary completion
- 28 Jun 2017 (actual)
- Study completion
- 28 Jun 2017 (actual)
- First posted
- 22 May 2012 (estimated)
- Results
- Posted 14 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and efficacy of BOTOX® (botulinum toxin Type A) in pediatric patients with lower limb spasticity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BOTOX® 4 U/kg | Experimental | Biological: botulinum toxin Type AParticipants 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 | Biological: botulinum toxin Type AParticipants 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 | Drug: 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. |
Who may qualify
- Ages
- 2 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Minimum weight of 10 kg/22 lb
- Cerebral palsy with dynamic muscle contracture /spasticity of the ankle
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| botulinum toxin Type AAlso: BOTOX®Participants received intramuscular injections of botulinum toxin Type A into specified muscles of the lower limb on Day 1. | Biological | BOTOX® 4 U/kg, BOTOX® 8 U/kg |
| Normal Saline (Placebo)Participants received intramuscular injections of normal saline (placebo) into specified muscles of the lower limb on Day 1. | Drug | Normal Saline (Placebo) |
Primary outcome
Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6
Time frame: 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
Time frame: 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.
2 secondary outcomes
Goal Attainment Score (GAS) as Assessed by Physician Using a 6-Point Scale
Time frame: 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)
Time frame: Baseline (Day 1) to Weeks 2, 4, 6, 8 and 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rozalina Dimitrova study director
Allergan
53 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing botulinum toxin Type A in people with Pediatrics and Muscle Spasticity, run by Allergan at 53 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, Poland, South Korea, Philippines, Russia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Change From Baseline in Modified Ashworth Scale-Bohannon (MAS-B) Ankle Score With Knee Extended at Weeks 4 and 6 (time frame: Baseline (Day 1) to Weeks 4 and 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2018.