Treatment With Xeomin Versus Botox in Children With Spastic Equine and Equinovarus Foot Deformation in Pediatric Cerebral Palsy (XEBEC)

Multi-center Open Comparative Randomized Trial of Clinical and Neurophysiological Efficacy and Safety of Xeomin (Botulinum Toxin Type A) vs. Botox (Complex of Botulinum Toxin Type A and Hemagglutinin) in Children With Spastic Equine and Equinovarus Foot Deformation in Pediatric Cerebral Palsy

1. To assess the clinical and neurophysiological efficacy of Xeomin® vs. Botox® in children with spastic equine and equinovarus foot deformation in pediatric cerebral palsy
2. To assess the safety of Xeomin® use as compared to Botox® in this patient population

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy; Spastic Paraplegia and Hemiparesis; Equine and Equinovarus Foot Deformation
• Intervention / Treatment: Drug: Xeomin; Drug: Botox®

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119602
    • State Budget Institution of Health in Moscow "Scientific and Practical Center of Pediatric psychoneurology Moscow Health Department"
  • Moscow, Russian Federation, 119991
    • Federal State Autonomous Institution "Scientific Center of Children's Health" of the Ministry of Health of the Russian Federation
  • Stavropol, Russian Federation, 355017
    • Federal State Budget Educational Institution of Higher Professional Learning "Stavropol State Medical University" of the Ministry of Health of the Russian Federation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children from 2 through 12 years of age, of both sexes, suffering from spastic paraplegia or hemiparesis in pediatric cerebral palsy.
• Equine and equinovarus foot posture.
• Gastrocnemius spasticity of 2 points and greater, by modified Ashworth scale.
• Patient can walk unassisted or with a support.
• Mental development of patients is normal or mildly retarded.
• Previous course of spasticity treatment with BTA products was completed earlier than at 6 months before this trial or never administered before.
• Patient's parents have signed an informed consent, are able and wishing to adhere to procedures described in the trial protocol and to the schedule of visits throughout the entire period of treatment.

Exclusion Criteria:

• Fixed ankle joint contracture.
• Previous denervation of spastic muscles by surgery, phenol or alcohol;
• Athetosis and dystonia in the area of injected muscles.
• Inflammation at the planned injection site.
• Elevated body temperature and acute (infectious and non-infectious) diseases at the time of injection.
• Neuromuscular transmission disorders (myasthenia gravis, Lambert-Eaton syndrome, etc.).
• Decompensated physical diseases potentially affecting the trial findings.
• Acute fever, infection or surgery within 1 month before the trial.
• Use of aminoglycosides or spectinomycin within 1 month before starting the trial.
• Hypersensitivity to any of product ingredients.
• Positive history for allergies (especially with regard to protein-containing products).
• Patient's parents are unable or unwilling to adhere to the trial protocol requirements including signing the informed consent and conforming to the schedule of visits.
• Participation in other clinical trials in the last 4 weeks before inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Xeomin®; 4-8 Units per kg body weight. Single injection cycle.	Drug: Xeomin; Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl). Administration route is intramuscular injection into medial (two points) and lateral heads (two points) of gastrocnemius.; Other Names: NT 201; Botulinum toxin type A (150 kiloDalton), free from complexing proteins; IncobotulinumtoxinA
ACTIVE_COMPARATOR: Botox®; 4-6(8) Units per kg body weight. Single injection cycle.	Drug: Botox®; Administration route is intramuscular injection into medial (two points) and lateral heads (two points) of gastrocnemius.; Other Names: OnabotulinumtoxinA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale (AS)	The AS is a well known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).	From baseline to day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in patient percentage in groups by the degree of gastrocnemius spasticity according to modified Ashworth scale		From baseline up to day 90
Percentage of decrease in M-response magnitude and area recorded from the lateral and medial gastrocnemius heads, from baseline values	Electromyography: The amplitude of a compound muscle action potential (M-wave) is recorded. An electrical stimulation is considered supramaximal when the M-wave amplitude no longer increases while increasing the stimulus. The measurements include the M-wave amplitude and the negative peak area of the M-wave.	From baseline up to day 90
Changes from baseline in the ratio of M-response recorded from the lateral and medial gastrocnemius heads and from tibialis anterior		From baseline up to day 90
Changes from baseline in angles and angle ratio of ankle joints at passive and voluntary extension		From baseline up to day 90
Changes from baseline in motor activity according to Gross Motor Function Classification Systems (GMFCS) criteria	GMFCS is a 5-level classification system that is a standardized observational instrument for children with CP developed to measure change in gross motor function over time.	From baseline up to day 90
Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale		Baseline up to day 90

Collaborators and Investigators

• Sponsor: Merz Pharmaceuticals GmbH
• Collaborators: LLC Merz Pharma, Russia
• Investigators: Study Director: Merz Medical Expert, LLC Merz Pharma, Russia

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: July 10, 2014
• First Submitted That Met QC Criteria: July 10, 2014
• First Posted (ESTIMATE): July 11, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): January 26, 2017
• Last Update Submitted That Met QC Criteria: January 25, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Brain Damage, Chronic; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Musculoskeletal Abnormalities; Paralysis; Muscle Hypertonia; Limb Deformities, Congenital; Foot Deformities; Foot Deformities, Acquired; Foot Deformities, Congenital; Lower Extremity Deformities, Congenital; Cerebral Palsy; Muscle Spasticity; Paresis; Clubfoot; Talipes; Equinus Deformity; Paraplegia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; incobotulinumtoxinA
• Other Study ID Numbers: MRZ-R-201212_01001_N_2