Clinical trial NCT01893411: Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Leg(s) in Cerebral Palsy
Official title: Prospective, Multicenter, Randomized, Double-blind, Parallel-group, Dose-response Study of Three Doses Xeomin® (incobotulinumtoxinA, NT 201) for the Treatment of Lower Limb Spasticity in Children and Adolescents (Age 2 - 17 Years) With Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lower Limb Spasticity Due to Cerebral Palsy
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2013-07-09
Enrollment: 311
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) are effective in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.


Eligibility criteria: Inclusion Criteria:

* Female or male subject of 2 to 17 years of age (inclusive).
* Uni- or bilateral cerebral palsy with clinical need for uni- or bilateral LL injections with BoNT for the treatment of spasticity.
* Ashworth Scale \[AS\] score ≥2 in plantar flexors (at least unilaterally).
* Clinical need for a total dose of 16 U/kg BW NT 201 (maximum of 400 U) for the treatment of LL spasticity according to the clinical judgment of the investigator.

Exclusion Criteria:

* Fixed contracture defined as severe restriction of the range of joint movement on passive stretch or predominant forms of muscle hypertonia other than spasticity (e.g., dystonia) in the target limb(s).
* Surgery on pes equinus on side(s) intended to be treated with BoNT injections in this study within 12 months prior to Screening Visit (V1), in the screening period or planned for the time of participation in this study.
* Hip flexion requiring BoNT injection.

Primary outcomes:
measure: Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC)
timeFrame: Baseline, Week 4
measure: Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle
timeFrame: Baseline, Week 4
Secondary outcomes:
measure: Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC)
timeFrame: Baseline, Week 4 of 1st IC and Week 16-40 of 2nd IC
measure: Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle
timeFrame: Baseline to Week 4 of 2nd IC (Week 16-40)
measure: Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle
timeFrame: Baseline to Week 8 and 12 of 1st IC and 2nd IC (Week 20-44 and 24-48)
measure: Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle
timeFrame: Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40)
measure: Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle
timeFrame: Baseline to Week 4, 8, and 12 of 1st IC and 2nd IC (Week 16-40, 20-44 and 24-48)
measure: Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle
timeFrame: Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40)
measure: Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle
timeFrame: Baseline to Week 4 of 1st IC and 2nd IC (Week 16-40)
measure: Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit
timeFrame: Baseline to Week 12-36 of 1st IC and 2nd IC (End of study = Week 24-72)
measure: Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle
timeFrame: Baseline to Week 4, 8, and 12 of 1st IC and 2nd IC (Week 16-40, 20-44 and 24-48)
measure: Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle
timeFrame: Baseline up to Week 24-72
measure: Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
timeFrame: Up to End of study visit (Week 24-72)
measure: Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle
timeFrame: Up to End of study visit (Week 24-72)
measure: Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle
timeFrame: Up to End of study visit (Week 24-72)
measure: Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle
timeFrame: Up to End of study visit (Week 24-72)
measure: Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle
timeFrame: Up to End of study visit (Week 24-72)
measure: Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle
timeFrame: Up to End of study visit (Week 24-72)
measure: Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle
timeFrame: Up to End of study visit (Week 24-72)
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Merz Investigational Site #043037
city: Vienna
country: Austria
facility: Merz Investigational Site #043036
city: Brno
country: Czechia
facility: Merz Investigational Site #420029
city: Olomouc
country: Czechia
facility: Merz Investigational Site #420028
city: Tallinn
country: Estonia
facility: Merz Investigational Site #372001
city: Tartu
country: Estonia
facility: Merz Investigational Site #372002
city: Amiens
country: France
facility: Merz Investigational Site #033056
city: Bron
country: France
facility: Merz Investigational Site #033052
city: La Tronche
country: France
facility: Merz Investigational Site #033054
city: Palavas-les-Flots
country: France
facility: Merz Investigational Site #033055
city: Bochum
country: Germany
facility: Merz Investigational Site #049328
city: Marburg
country: Germany
facility: Merz Investigational Site #049330
city: Muenster
country: Germany
facility: Merz Investigational Site #049329
city: Munich
country: Germany
facility: Merz Investigational Site #049327
city: Vogtareuth
country: Germany
facility: Merz Investigational Site #049326
city: Jerusalem
country: Israel
facility: Merz Investigational Site #972003
city: Tel Aviv
country: Israel
facility: Merz Investigational Site #972001
city: Tel Aviv
country: Israel
facility: Merz Investigational Site #972002
city: Goyang
country: Korea, Republic of
facility: Merz Investigational Site #082019
city: Incheon
country: Korea, Republic of
facility: Merz Investigational Site #082021
city: Seongnam-si
country: Korea, Republic of
facility: Merz Investigational Site #082018
city: Seoul
country: Korea, Republic of
facility: Merz Investigational Site #082020
city: Bialystok
country: Poland
facility: Merz Investigational Site #048089
city: Gdansk
country: Poland
facility: Merz Investigational Site #048063
city: Kraków
country: Poland
facility: Merz Investigational Site #048059
city: Lublin
country: Poland
facility: Merz Investigational Site #048084
city: Lubon
country: Poland
facility: Merz Investigational Site #048072
city: Sandomierz
country: Poland
facility: Merz Investigational Site #048075
city: Warsaw
country: Poland
facility: Merz Investigational Site #048061
city: Bucharest
country: Romania
facility: Merz Investigational Site #040003
city: Bucharest
country: Romania
facility: Merz Investigational Site #040001
city: Iasi
country: Romania
facility: Merz Investigational Site #040002
city: Kazan
country: Russian Federation
facility: Merz Investigational Site #007014
city: Khabarovsk
country: Russian Federation
facility: Merz Investigational Site #007015
city: Novosibirsk
country: Russian Federation
facility: Merz Investigational Site #007018
city: Saint-Petersburg
country: Russian Federation
facility: Merz Investigational Site #007017
city: Smolensk
country: Russian Federation
facility: Merz Investigational Site #007013
city: Stavropol
country: Russian Federation
facility: Merz Investigational Site #007019
city: Banska Bystrica
country: Slovakia
facility: Merz Investigational Site #421003
city: Bratislava
country: Slovakia
facility: Merz Investigational Site #421008
city: Krompachy
country: Slovakia
facility: Merz Investigational Site #421006
city: Levoca
country: Slovakia
facility: Merz Investigational Site #421004
city: Granada
country: Spain
facility: Merz Investigational Site #034031
city: Manresa
country: Spain
facility: Merz Investigational Site #034032
city: Sevilla
country: Spain
facility: Merz Investigational Site #034030
city: Sevilla
country: Spain
facility: Merz Investigational Site #034026
city: Elazig
country: Turkey
facility: Merz Investigational Site #090005
city: Izmir
country: Turkey
facility: Merz Investigational Site #090003
city: Izmit
country: Turkey
facility: Merz Investigational Site #090002
city: Dnipropetrovsk
country: Ukraine
facility: Merz Investigational Site #380001
city: Kharkiv
country: Ukraine
facility: Merz Investigational Site #380005
city: Kiev
country: Ukraine
facility: Merz Investigational Site #380002
city: Odessa
country: Ukraine
facility: Merz Investigational Site #380003
Study officials:
affiliation: Merz Pharmaceuticals GmbH
name: Merz Medical Expert
role: STUDY_DIRECTOR
References:
citation: Heinen F, Kanovsky P, Schroeder AS, Chambers HG, Dabrowski E, Geister TL, Hanschmann A, Martinez-Torres FJ, Pulte I, Banach M, Gaebler-Spira D. IncobotulinumtoxinA for the treatment of lower-limb spasticity in children and adolescents with cerebral palsy: A phase 3 study. J Pediatr Rehabil Med. 2021;14(2):183-197. doi: 10.3233/PRM-210040.
citation: Berweck S, Banach M, Gaebler-Spira D, Chambers HG, Schroeder AS, Geister TL, Althaus M, Hanschmann A, Vacchelli M, Bonfert MV, Heinen F, Dabrowski E. Safety Profile and Lack of Immunogenicity of IncobotulinumtoxinA in Pediatric Spasticity and Sialorrhea: A Pooled Analysis. Toxins (Basel). 2022 Aug 25;14(9):585. doi: 10.3390/toxins14090585.