BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01603615
• Collaborator: (none)
• Enrollment: 220
• Locations: 48
• Arm: 1
• Actual Duration (Months): 70.1
• Patients Per Site: 4.6
• 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 upper limb spasticity.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 220 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BOTOX® Treatment in Pediatric Upper Limb Spasticity: Open-label Study
• Actual Study Start Date: Oct 30, 2012
• Actual Primary Completion Date: Sep 3, 2018
• Actual Study Completion Date: Sep 3, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: BOTOX® Participants received a maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into upper limb and/or lower limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment, de novo participants received at least 6 U/kg of body weight or a maximum of 8 U/kg of body weight (not to exceed 300 U). Rollover participants received up to a maximum of 8 U/kg of body weight (not to exceed 300 U) for treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Rolled over participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 or 6 U/kg into upper limb in previous study or were de novo participants who were not enrolled in previous study.

Biological: Botulinum Toxin Type A; Participants received intramuscular injections of botulinum Toxin Type A in the upper and/or lower 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. Safety population included all treated participants.

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)

• 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 3 months

• History of surgical intervention of the upper limb 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 Dept. of PM&R	Aurora	Colorado	United States	80045
5	Associated Neurologists of Southern Connecticut, P.C.	Fairfield	Connecticut	United States	06824
6	New England Center 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, PA	Orlando	Florida	United States	32891
10	Children's Healthcare of Atlanta Children's Rehabilitation Associates	Atlanta	Georgia	United States	30342
11	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota	United States	55101
12	The Children's Mercy Hospital & Clinics	Kansas City	Missouri	United States	64108
13	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
14	Clinical Research Center of New Jersey	Voorhees	New Jersey	United States	08043
15	NYU Hospital for Joint Diseases	New York	New York	United States	10003
16	Columbia University Pediatric Physical Medicine & Rehabilitation, Dept. of Rehabilitation & Regenerative Medicine Harkness	New York	New York	United States	10032
17	OnSite Clinical Solutions, LLC	Charlotte	North Carolina	United States	28203
18	PMG Research of Charlotte, LLC	Charlotte	North Carolina	United States	28203
19	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
20	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235
21	Baylor College of Medicine Texas Children's Hospital	Houston	Texas	United States	77030
22	Road Runner Research	San Antonio	Texas	United States	78249
23	Seattle Children's Hospital	Seattle	Washington	United States	98105
24	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
25	Holland Bloorview Kids Rehab	Toronto	Ontario	Canada	M4G 1R8
26	Debrecen University Clinical Center, Orthopedic Clinic	Debrecen		Hungary	4032
27	Daegu Fatima Hospital	Daegu		Korea, Republic of	41199
28	National Health Insurance Service Ilsan Hospital	Gyeonggi-do		Korea, Republic of	10444
29	Seoul National University Hospital	Seoul		Korea, Republic of	03080
30	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
31	Asan Medical Center	Seoul		Korea, Republic of	05505
32	Samsung Medical Center	Seoul		Korea, Republic of	06351
33	De La Salle Health Sciences Institute	Cavite		Philippines	4114
34	Philippine Children's Medical Center	Quezon City		Philippines	1104
35	Uni Centrum Kliniczne	Gdansk		Poland	80-219
36	Specjal. Gabinet Neurologiczny	Krakow		Poland	30-539
37	Centrum Medyczne "POMOC"	Lodz		Poland	93-271
38	INTERMED, Lublin	Lublin		Poland	20-058
39	CRH ŻAGIEL MED, Lublin	Lublin		Poland	20-601
40	Centrum Profilatyki I Terapii	Warsaw		Poland	02-383
41	NZOZ Mazowieckie Centrum	Warsaw		Poland	05-462
42	Childrens Republic Hospital	Kazan		Russian Federation	420138
43	Smolensk Regional Hospital- Regional Budget State Healthcare institution	Smolensk		Russian Federation	214018
44	Tyumen Regional Hospital #2 - State Budget Healthcare Institution of Tyumen region	Tyumen		Russian Federation	625039
45	Siriraj Hospital Dept of Rehabilitation Medicine, Faculty of Medicine	Bangkok		Thailand	10700
46	Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University	Chiang Mai		Thailand	50200
47	Srinagarind Hospital, Khon Kaen University	Khon Kaen		Thailand	40002
48	Kocaeli Üniversitesi	Kocaeli		Turkey	41050

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Emily McCusker, Allergan

Study Documents (Full-Text)

• Study Protocol - Aug 1, 2016
• Statistical Analysis Plan - Jan 14, 2019

More Information

Additional Information:

• More information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT01603615
• Other Study ID Numbers: 191622-105; 2012-000043-27
• 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 Upper Limb Spasticity who were previously treated with BOTOX® in study 191622-101 [NCT01603602] and de novo participants received up to 5 BOTOX® treatments in this study.

Arm/Group Title	BOTOX®
Arm/Group Description	Participants received a maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into upper limb and/or lower limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment, de novo participants received at least 6 U/kg of body weight or a maximum of 8 U/kg of body weight (not to exceed 300 U). Rollover participants received up to a maximum of 8 U/kg of body weight (not to exceed 300 U) for treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Rolled over participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 or 6 U/kg into upper limb in previous study or were de novo participants who were not enrolled in previous study.
Period Title: Overall Study
STARTED	220
Safety Population (Treated)	213
COMPLETED	186
NOT COMPLETED	34

Baseline Characteristics

Arm/Group Title	BOTOX®
Arm/Group Description	Participants received a maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into upper limb and/or lower limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment, de novo participants received at least 6 U/kg of body weight or a maximum of 8 U/kg of body weight (not to exceed 300 U). Rollover participants received up to a maximum of 8 U/kg of body weight (not to exceed 300 U) for treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Rolled over participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 or 6 U/kg into upper limb in previous study or were de novo participants who were not enrolled in previous study.
Overall Participants	213
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.3 (4.1)
Sex: Female, Male (Count of Participants)
Female	85 39.9%
Male	128 60.1%
Race/Ethnicity, Customized (Count of Participants)
White	130 61%
Black	9 4.2%
Asian	61 28.6%
Hispanic	10 4.7%
Other	3 1.4%

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. Safety population included all treated participants.
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 a maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into upper limb and/or lower limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment, de novo participants received at least 6 U/kg of body weight or a maximum of 8 U/kg of body weight (not to exceed 300 U). Rollover participants received up to a maximum of 8 U/kg of body weight (not to exceed 300 U) for treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Rolled over participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 or 6 U/kg into upper limb in previous study or were de novo participants who were not enrolled in previous study.
Measure Participants	213
Number [percentage of participants]	58.7 27.6%

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 a maximum of 5 treatments of intramuscular injections of BOTOX® (botulinum toxin Type A) into upper limb and/or lower limb muscles at a minimum of 12 weeks apart. Treatment dosing was according to investigator judgment, de novo participants received at least 6 U/kg of body weight or a maximum of 8 U/kg of body weight (not to exceed 300 U). Rollover participants received up to a maximum of 8 U/kg of body weight (not to exceed 300 U) for treatment Cycle 1. Dose could be increased to a maximum of 10 U/kg (not to exceed 340 U) in treatment Cycles 2-5. Rolled over participants received intramuscular injections of BOTOX® (botulinum toxin Type A) 3 or 6 U/kg into upper limb in previous study or were de novo participants who were not enrolled in previous study.
All Cause Mortality
	BOTOX®
	Affected / at Risk (%)	# Events
Total	0/213 (0%)
Serious Adverse Events
	BOTOX®
	Affected / at Risk (%)	# Events
Total	13/213 (6.1%)
Congenital, familial and genetic disorders
Cryptorchism	1/213 (0.5%)
Gastrointestinal disorders
Food poisoning	1/213 (0.5%)
Dental caries	1/213 (0.5%)
Infections and infestations
Gastroenteritis	1/213 (0.5%)
Pneumonia	1/213 (0.5%)
Respiratory tract infection viral	1/213 (0.5%)
Meningitis	1/213 (0.5%)
Metabolism and nutrition disorders
Dehydration	1/213 (0.5%)
Hypoglycaemia	1/213 (0.5%)
Musculoskeletal and connective tissue disorders
Joint contracture	1/213 (0.5%)
Juvenile idiopathic arthritis	1/213 (0.5%)
Nervous system disorders
Epilepsy	2/213 (0.9%)
Hemiplegia	1/213 (0.5%)
Seizure	1/213 (0.5%)
Status epilepticus	1/213 (0.5%)
Partial seizures	1/213 (0.5%)
Other (Not Including Serious) Adverse Events
	BOTOX®
	Affected / at Risk (%)	# Events
Total	57/213 (26.8%)
Infections and infestations
Upper respiratory tract infection	29/213 (13.6%)
Nasopharyngitis	22/213 (10.3%)
Respiratory, thoracic and mediastinal disorders
Cough	13/213 (6.1%)

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.