BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01603641
• Collaborator: (none)
• Enrollment: 370
• Locations: 56
• Arm: 1
• Actual Duration (Months): 69.6
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the long-term safety of BOTOX® (botulinum toxin Type A) for the treatment of pediatric lower limb spasticity.

Condition or Disease	Intervention/Treatment	Phase
Pediatrics; Muscle Spasticity; Cerebral Palsy	Biological: Botulinum Toxin Type A	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 370 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BOTOX® Treatment in Pediatric Lower Limb Spasticity: Open-label Study
• Actual Study Start Date: Nov 5, 2012
• Actual Primary Completion Date: Aug 25, 2018
• Actual Study Completion Date: Aug 25, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: BOTOX® Participants received maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into a single lower limb muscles or divided between both lower limb muscles or into the lower limb muscles and/or upper limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment not to exceed a maximum of 8 unit per kilogram (U/kg) of body weight (not to exceed 300 U) in treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 or 8 U/kg into the lower limb in the previous study or were de novo participants who were not enrolled in the previous study.

Biological: Botulinum Toxin Type A; Participants received intramuscular injections of botulinum toxin Type A into the lower limb muscles and/or upper limb muscles at a minimum of 12 weeks apart for a maximum of 5 treatments.; Other Names: BOTOX® OnabotulinumtoxinA

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) [From first dose of study drug up to 12 weeks post last dose (Up to 60 weeks)]

   An adverse event (AE) was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A TEAE was an AE that occurred after receiving the first dose of investigational product or an AE present prior to first dose but increased in severity during the Treatment Period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Minimum weight of 10 kilograms (kg)/22 pounds (lb)

• Cerebral palsy with dynamic muscle contracture of the ankle

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 3 months

• History of surgical intervention of the lower study leg within 1 year, or planned surgery of any limb during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ABS Health, LLC	Pasadena	California	United States	91106
2	Harrison Clinical Management	Pomona	California	United States	91767
3	Rady Children's Hospital San Diego	San Diego	California	United States	92123
4	Children's Hospital Colorado	Aurora	Colorado	United States	80045
5	Associated Neurologists of Southern Connecticut, P.C.	Fairfield	Connecticut	United States	06824
6	New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
7	NW FL Clinical Research Group, LLC	Gulf Breeze	Florida	United States	32561
8	Axcess Medical Research, LLC	Loxahatchee Groves	Florida	United States	33470
9	Pediatric Neurology, P.A.	Orlando	Florida	United States	32819
10	Children's Healthcare of Atlanta Children's Rehabilitation Associates	Atlanta	Georgia	United States	30342
11	Shirley Ryan Ability Lab	Chicago	Illinois	United States	60611
12	Beaumont Children's Hospital Pediatric Research	Royal Oak	Michigan	United States	48073
13	The Children's Mercy Hospital	Kansas City	Missouri	United States	64108
14	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
15	Clinical Research Center of New Jersey	Voorhees	New Jersey	United States	08043
16	NYU Hospital for Joint Diseases	New York	New York	United States	10003
17	Columbia University Dept. of Rehab. & Regenerative Medicine	New York	New York	United States	10032
18	OnSite Clinical Solutions, LLC	Charlotte	North Carolina	United States	28203
19	PMG Research of Charlotte, LLC	Charlotte	North Carolina	United States	28203
20	Hasbro Children's Hospital	Providence	Rhode Island	United States	02903
21	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
22	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
23	Baylor College of Medicine Texas Children's Hospital	Houston	Texas	United States	77030
24	Road Runner Research	San Antonio	Texas	United States	78249
25	Seattle Children's Hospital	Seattle	Washington	United States	98105
26	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
27	Semmelweis Egyetem- Ortopédiai Klinika Karolina út 27	Budapest		Hungary	1113
28	Debrecen University Clinical Center, Orthopedic Clinic	Debrecen		Hungary	4032
29	Istituto IRCCS G. Salini	Genoa		Italy	16148
30	Daegu Fatima Hospital	Daegu		Korea, Republic of	41199
31	National Health Insurance Service Ilsan Hospital	Gyeonggi-do		Korea, Republic of	10444
32	Seoul National University Hospital	Seoul		Korea, Republic of	03080
33	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
34	Asan Medical Center	Seoul		Korea, Republic of	05505
35	Samsung Medical Center	Seoul		Korea, Republic of	06351
36	Philippine Orthopedic Center	Quezon City		Philippines	1100
37	St. Luke's Medical Center	Quezon City		Philippines	1102
38	Philippine Children's Medical Center	Quezon City		Philippines	1104
39	Uniwersytecki Dzieciecy Szpita	Białystok		Poland	15-274
40	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-219
41	Centrum Rehabilitacji Krok po Kroku	Gdansk		Poland	80-389
42	Specjalistyczny Gabinet Neurologiczny	Krakow		Poland	30-539
43	Centrum Medyczne "POMOC"	Lodz		Poland	93-271
44	INTERMED, Lublin	Lublin		Poland	20-058
45	CRH ŻAGIEL MED, Lublin	Lublin		Poland	20-601
46	Szpital Wojewodzki Nr 2	Rzeszow		Poland	35-301
47	Poradnia Rehab - Neurologiczneij dla Dzieci I Mlodziezy Aga	Warsaw		Poland	02-315
48	NZOZ Mazowieckie Centrum	Warsaw		Poland	05-462
49	Childrens Republic Hospital	Kazan		Russian Federation	420138
50	Smolensk Regional Hospital- Regional Budget State Healthcare institution	Smolensk		Russian Federation	214018
51	Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region	Tyumen		Russian Federation	625039
52	Maharaj Nakorn ChiangMai Hospital	ChiangMai		Thailand	50200
53	Srinagarind Hospital, Khon Kaen University	Khon Kaen		Thailand	40002
54	Ankara Diskapi Yildrim Beyazit	Ankara		Turkey	6110
55	Kocaeli Üniversitesi	Kocaeli		Turkey	41050
56	Selçuk Üniversitesi	Konya		Turkey	42250

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Emily McCusker, Allergan

Study Documents (Full-Text)

• Study Protocol - Jan 28, 2014
• Statistical Analysis Plan - Oct 2, 2018

More Information

Additional Information:

• More information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01603641
• Other Study ID Numbers: 191622-112; 2012-000084-24
• First Posted: May 22, 2012
• Last Update Posted: Aug 21, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Muscle Spasticity; Cerebral Palsy; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Pre-assignment Detail	Pediatric participants with lower limb spasticity who were previously treated with BOTOX® in study 191622-111 [NCT01603628] and de novo participants received up to 5 BOTOX® treatments in this study.

Arm/Group Title	BOTOX®
Arm/Group Description	Participants received maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into a single lower limb muscles or divided between both lower limb muscles or into the lower limb muscles and/or upper limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment not to exceed a maximum of 8 unit per kilogram (U/kg) of body weight (not to exceed 300 U) in treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 or 8 U/kg into the lower limb in the previous study or were de novo participants who were not enrolled in the previous study.
Period Title: Overall Study
STARTED	370
Safety Population (Treated)	367
Modified Intent-to-treat Population	366
COMPLETED	335
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	BOTOX®
Arm/Group Description	Participants received maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into a single lower limb muscles or divided between both lower limb muscles or into the lower limb muscles and/or upper limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment not to exceed a maximum of 8 unit per kilogram (U/kg) of body weight (not to exceed 300 U) in treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 or 8 U/kg into the lower limb in the previous study or were de novo participants who were not enrolled in the previous study.
Overall Participants	367
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.9 (3.8)
Sex: Female, Male (Count of Participants)
Female	167 45.5%
Male	200 54.5%
Race/Ethnicity, Customized (Count of Participants)
White	224 61%
Black	9 2.5%
Asian	109 29.7%
Hispanic	21 5.7%
Other	4 1.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
Description	An adverse event (AE) was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A TEAE was an AE that occurred after receiving the first dose of investigational product or an AE present prior to first dose but increased in severity during the Treatment Period.
Time Frame	From first dose of study drug up to 12 weeks post last dose (Up to 60 weeks)

Outcome Measure Data

Analysis Population Description

Safety population included all treated participants.

Arm/Group Title	BOTOX®
Arm/Group Description	Participants received maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into a single lower limb muscles or divided between both lower limb muscles or into the lower limb muscles and/or upper limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment not to exceed a maximum of 8 unit per kilogram (U/kg) of body weight (not to exceed 300 U) in treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 or 8 U/kg into the lower limb in the previous study or were de novo participants who were not enrolled in the previous study.
Measure Participants	367
Number [percentage of participants]	65.4 17.8%

Adverse Events

Time Frame	From first dose of study drug up to 12 weeks post last dose (Up to 60 weeks)
Adverse Event Reporting Description	Safety Population included all treated participants.
Arm/Group Title	BOTOX®
Arm/Group Description	Participants received maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into a single lower limb muscles or divided between both lower limb muscles or into the lower limb muscles and/or upper limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment not to exceed a maximum of 8 unit per kilogram (U/kg) of body weight (not to exceed 300 U) in treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 4 or 8 U/kg into the lower limb in the previous study or were de novo participants who were not enrolled in the previous study.
All Cause Mortality
	BOTOX®
	Affected / at Risk (%)	# Events
Total	0/367 (0%)
Serious Adverse Events
	BOTOX®
	Affected / at Risk (%)	# Events
Total	24/367 (6.5%)
Cardiac disorders
Arrhythmia	1/367 (0.3%)
Eye disorders
Entropion	1/367 (0.3%)
Strabismus	1/367 (0.3%)
Cataract	1/367 (0.3%)
Infections and infestations
Pharyngitis	4/367 (1.1%)
Pneumonia	4/367 (1.1%)
Laryngitis	1/367 (0.3%)
Tonsillitis	1/367 (0.3%)
Bronchitis	2/367 (0.5%)
Investigations
Aspartate aminotransferase increased	1/367 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer	1/367 (0.3%)
Nervous system disorders
Febrile convulsion	4/367 (1.1%)
Hemiplegia	2/367 (0.5%)
Seizure	2/367 (0.5%)
Status epilepticus	2/367 (0.5%)
Epilepsy	1/367 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/367 (0.3%)
Other (Not Including Serious) Adverse Events
	BOTOX®
	Affected / at Risk (%)	# Events
Total	145/367 (39.5%)
General disorders
Pyrexia	27/367 (7.4%)
Infections and infestations
Upper respiratory tract infection	67/367 (18.3%)
Nasopharyngitis	65/367 (17.7%)
Bronchitis	21/367 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.