To view videos of the children at baseline and after onabotulinumtoxinA treatment please follow the links below

Girl Baseline httpsvimeocom2920639122e2f236b16

Girl Week 8 httpsvimeocom292064448c160a01b48

Boy Baseline httpsvimeocom2920646274df87f9ea7

Boy Week 8 httpsvimeocom2920647954ed44475de

Efficacy and Safety of OnabotulinumtoxinAfor the Treatment of Pediatric Lower Limb Spasticity Primary ResultsHeakyung Kim1 Jill Meilahn2 Chengcheng Liu3 Henry G Chambers4 Emily McCusker5Rozalina Dimitrova5

1Columbia University Medical CenterNew York Presbyterian Hospital New York NY USA 2Marshfield Clinic Marshfield WI USA 3Allergan plc Madison NJ USA 4Rady Childrenrsquos Specialists of San Diego San Diego CA USA 5Allergan plc Irvine CA USA

This study was sponsored by Allergan plc Dublin Ireland Writing and editorial assistance was provided to the authors by Karen Pemberton PhD of Evidence Scientifi c Solutions Inc and funded by Allergan plc All authors met the ICMJE authorship criteria Neither honoraria nor payments were made for authorship Financial arrangements of the authors with companies whose products may be related to the present report are listed below as declared by the authors

HK has received grantresearch support from Allergan plc and Ipsen JM and HGC have no fi nancial disclosures to report CL EM and RD are employees and shareholders of Allergan plc

References1 Shamsoddini A et al Iran J Pediatr 201424(4)345ndash3512 Koman LA et al Lancet 2004363(9421)1619ndash16313 BOTOXreg (onabotulinumtoxinA) for injection for intramuscular

intradetrusor or intradermal use Irvine CA Allergan 20164 Bohannon RW and Smith MB Phys Ther 198767(2)206ndash2075 Guy W ECDEU Assessment Manual Rockville MD US

Department of Health Education and Welfare 19766 Ansari NN et al Brain Inj 201327(5)605ndash6127 Borg J et al J Rehabil Med 201143(1)15ndash22

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EFFICACY AND SAFETY OF ONABOTULINUMTOXINA FOR THE TREATMENT OF PEDIATRIC LOWER LIMB SPASTICITYPRIMARY RESULTSHeakyung Kim1 Jill Meilahn2 Chengcheng Liu3 Henry G Chambers4

Emily McCusker5 Rozalina Dimitrova5

1Columbia University Medical CenterNew York Presbyterian Hospital New York NY USA 2Marshfi eld Clinic Marshfi eld WI USA 3Allergan plc Madison NJ USA 4Rady Childrens Specialists of San Diego San Diego CA USA 5Allergan plc Irvine CA USA

To obtain a PDF of this poster and to view videos of children at baseline and after onabotulinumtoxinA treatmentbull Scan the QR code

OR bull Visit wwwallergancongressposterscom550370Charges may apply No personal information is stored

Presented at TOXINS 2019 the 4th International Congress of the International Neurotoxin Association (INA) January 16ndash19 2019 Copenhagen Denmark

Backgroundbull Spasticity is a common

impairment in children with cerebral palsy impeding function worsening quality of life and causing pain12

bull The safety and effi cacy of onabotulinumtoxinA treatment have been established in adult patients with muscle spasticity3

Objectivebull To evaluate the safety and

effi cacy of onabotulinumtoxinA for lower limb spasticityhypertonia in children with cerebral palsy

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S Baseline Demographics and Disease Characteristics bull Baseline demographics and disease characteristics were generally balanced

across treatment groups (Table 2)

Table 2 Baseline demographics and disease characteristics

Study Designbull Phase 3 randomized double-blind placebo-controlled study

(Clinicaltrialsgov identifi er NCT01603628) (Table 1 Figure 1)

Assessmentsbull Primary outcome measure

Change from baseline in Modifi ed Ashworth Scale (MAS)4

ankle score at weeks 4 and 6 (average change from baseline)bull Secondary outcome measures

Clinical Global Impression of Change (CGI)5

Change in Modifi ed Tardieu Scale6

Goal Attainment Score7

bull Other measures Edinburgh Visual Gait Score

bull Safety and tolerability of treatments were also assessed

Table 1 General overview of lower limb pediatric study

12 Weeks9631 2 4 5 7 8 10 11

Primary endpointAverage of

weeks 4 and 6

Randomization and treatment

Screening MAS ge2 of ankleOnabotulinumtoxinA 8 Ukg + PT

OnabotulinumtoxinA 4 Ukg + PT

Placebo + PT

MAS = Modifi ed Ashworth Scale PT = physical therapy

Figure 1 Study design

OnabotulinumtoxinA in conjunction with standardized physical therapy

was safe and effective in treating lower limb spasticity in pediatric patients

with cerebral palsy

Statistically signifi cant improvement in the primary and secondary outcomes was observed with

onabotulinumtoxinA over standardized physical therapy alone

The safety profi le of onabotulinumtoxinA was

similar to that with placebo and no new safety signals

were identifi ed

Patientsindication Spasticity in ankle

Medically stable monoplegic or hemiplegic children

Aged 2ndashlt17 years with spasticity due to cerebral palsy

Duration Double-blind 12-week trial

InterventionsOnabotulinumtoxinA 4 UkgOnabotulinumtoxinA 8 Ukg + Standardized physical therapyPlacebo

Muscle injection required

GastrocnemiusSoleusTibialis posterior

GastrocnemiusCalfmuscles

Soleus

Achilles tendon

OnabotA 8 Ukg(n=127)

OnabotA 4 Ukg(n=125)

Placebo (n=129)

Total (N=381)

Mean (SD) age y 67 (39) 64 (36) 67 (39) 66 (38)le6 n () 74 (583) 73 (584) 74 (574) 221 (580)gt6 n () 53 (417) 52 (416) 55 (426) 160 (420)

Male n () 70 (551) 67 (536) 69 (535) 206 (541)Race n ()

White 76 (598) 76 (608) 79 (612) 231 (606)Asian 42 (331) 35 (280) 37 (287) 114 (299)Other 9 (71) 14 (112) 13 (101) 36 (94)

Hemiplegia n ()a 110 (866) 109 (872) 110 (853) 329 (864)Mean (SD) MAS ankle derived score knee extendedb

35 (052) 35 (053) 35 (050)

GMFCS ndash E and R n ()Level 1 69 (539) 65 (516) 65 (508) 199 (518)Level 2 54 (422) 51 (405) 56 (438) 163 (422)Levels 3 and 4 5 (39) 10 (80) 7 (55) 22 (57)

aAll others had monoplegia bMAS scale was converted from a 0ndash4 to 1ndash5 scaleGMFCS ndash E and R = Gross Motor Function Classifi cation System ndash Expanded and Revised MAS = Modifi ed Ashworth Scale OnabotA = OnabotulinumtoxinA SD = standard deviation

Effi cacy Outcomesbull OnabotulinumtoxinA 8 Ukg and 4 Ukg reduced (improved) average MAS-ankle

scores at weeks 4 and 6 compared with baseline Compared with the placebo group the change in MAS-ankle scores from

baseline were signifi cantly improved for both onabotulinumtoxinA treatment groups (Figure 2)

bull OnabotulinumtoxinA 8 Ukg and 4 Ukg increased (improved) average CGI scores at weeks 4 and 6

The increase with the 8-Ukg dose was statistically signifi cant (Figure 3)

Figure 2 OnabotulinumtoxinA reduces spasticity over the standard of care physical therapy

Figure 3 OnabotulinumtoxinA improves CGI over the standard of care physical therapy

Statistically signifi cant vs placeboMAS = Modifi ed Ashworth Scale OnabotA = onabotulinumtoxinA

Statistically signifi cant vs placeboCGI = Clinical Global Impression of Change OnabotA = onabotulinumtoxinA

Impr

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MA

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exte

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OnabotA8 Ukg

OnabotA4 Ukg Placebo

P=010

P=033

Impr

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08

12

10

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OnabotA8 Ukg

OnabotA4 Ukg

Placebo

P=023 P=229

bull Both doses of onabotulinumtoxinA demonstrated signifi cant reduction in muscle tone (MAS scores) from baseline throughout the course of the study compared with placebo (Figure 4A)

bull A greater treatment response (CGI as determined by the physician) was observed at weeks 2 4 and 6 with onabotulinumtoxinA compared with placebo (Figure 4B)

Figure 4 OnabotulinumtoxinA demonstrates sustained improvement in (A) MAS and (B) CGI

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OnabotA 8 UkgOnabotA 4 UkgPlacebo

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OnabotA 8 UkgOnabotA 4 UkgPlacebo

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Safety and Tolerabilitybull The incidence of adverse events with onabotulinumtoxinA was

similar to that with placebo (Table 3)bull No new safety signals were identifi ed

Table 3 Safety and tolerability

AEs n ()OnabotA 8 Ukg

(n=128)OnabotA 4 Ukg

(n=126)All OnabotA

(n=254)Placebo (n=128)

Treatment-emergent AEs 56 (438) 54 (429) 110 (433) 63 (492)

SAEs 0 3 (24)a 3 (12) 4 (31)b

Treatment-related AEs 4 (31) 3 (24) 7 (28) 2 (16)

Treatment-related SAEs 0 0 0 0

Discontinued owing to AE 0 0 0 0

Deaths 0 0 0 0aSAEs included cardiac disorders (extrasystole and tachycardia) seizure and tonsillar hypertrophy bSAEs included gastroenteritis seizure (n=2) and radicular painAE = adverse event OnabotA = OnabotulinumtoxinA SAE = serious adverse event

bull With the knee extended both doses of onabotulinumtoxinA signifi cantly improved the dynamic component of spasticity (Figure 6)

Both doses of onabotulinumtoxinA improved fast motion angle (R1) and slow motion angle (R2) measures

bull Similar results were observed when the knee was fl exedbull In a subset of patients who completed the assessment

onabotulinumtoxinA 8 Ukg demonstrated statistically signifi cant improvement in Edinburgh Visual Gait Total Score at week 8 (Figure 7)

bull The photographs in Figure 8 show representative examples of the improvement in gait seen with onabotulintoxinA

Figure 6 OnabotulinumtoxinA reduces dynamic tone (MTS)

Figure 5 OnabotulinumtoxinA improves active and passivefunctional goal attainment

Statistically signifi cant vs placeboMTS = Modifi ed Tardieu Scale OnabotA = onabotulinumtoxinA R2-R1 = difference between slow motion angle (R2) and fast motion angle (R1)

Statistically signifi cant vs placeboOnabotA = onabotulinumtoxinA

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12 8 12 Week

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Meetsexpectation

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P=005P=047

P=001

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OnabotA 8 UkgOnabotA 4 UkgPlacebo

Goa

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P=02

P=006

OnabotA 8 UkgOnabotA 4 UkgPlacebo

Figure 7 OnabotulinumtoxinA improves gait more than physical therapy alone

Figure 8 Photos representative of the improvements seen ingait following treatment with OnabotulinumtoxinA

Statistically signifi cant vs placeboOnabotA = onabotulinumtoxinA

MAS = Modifi ed Ashworth Scale OnabotA = onabotulinumtoxinA

-40

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8 12Week

Impr

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P=018

OnabotA 8 Ukg (n=26)OnabotA 4 Ukg (n=20)Placebo (n=17)

A 2-year-old male MASbaseline=3 MASweek 8=1OnabotA 8 Ukg

Week 8BaselinePlease scan QR code below to view videos of these children

B 2-year-old female MASbaseline=3 MASweek 8=2OnabotA 4 Ukg

Week 8BaselinePlease scan QR code below to view videos of these children

bull OnabotulinumtoxinA 8 Ukg and 4 Ukg both demonstrated greater active (eg walking speed endurance balance improved gait) and passive (eg pain tolerance of orthotic devices reduction in care needs) goal achievements than placebo (Figure 5)

Statistically signifi cant vs placeboCGI = Clinical Global Impression of Change MAS = Modifi ed Ashworth Scale OnabotA = onabotulinumtoxinA

SUM

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