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

• ClinicalTrials.gov Identifier: NCT02188277
• Recruitment Status: Completed
• First Posted: July 11, 2014
• Last Update Posted: January 26, 2017
• Sponsor: Merz Pharmaceuticals GmbH
• Collaborator: LLC Merz Pharma, Russia
• Information provided by (Responsible Party): Merz Pharmaceuticals GmbH

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cerebral Palsy; Spastic Paraplegia and Hemiparesis; Equine and Equinovarus Foot Deformation	Drug: Xeomin; Drug: Botox®	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: July 2014
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: December 2016

Arms and Interventions

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: IncobotulinumtoxinA; NT 201; Botulinum toxin type A (150 kiloDalton), free from complexing proteins
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 Name: OnabotulinumtoxinA

Outcome Measures

Primary Outcome Measures :

1. Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale (AS) [ Time Frame: From baseline to day 30 ]
   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).

Secondary Outcome Measures :

1. Changes from baseline in patient percentage in groups by the degree of gastrocnemius spasticity according to modified Ashworth scale [ Time Frame: From baseline up to day 90 ]
2. Percentage of decrease in M-response magnitude and area recorded from the lateral and medial gastrocnemius heads, from baseline values [ Time Frame: From baseline up to day 90 ]
   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.
3. Changes from baseline in the ratio of M-response recorded from the lateral and medial gastrocnemius heads and from tibialis anterior [ Time Frame: From baseline up to day 90 ]
4. Changes from baseline in angles and angle ratio of ankle joints at passive and voluntary extension [ Time Frame: From baseline up to day 90 ]
5. Changes from baseline in motor activity according to Gross Motor Function Classification Systems (GMFCS) criteria [ Time Frame: From baseline up to day 90 ]
   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.
6. Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale [ Time Frame: Baseline up to day 90 ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Russian Federation

State Budget Institution of Health in Moscow "Scientific and Practical Center of Pediatric psychoneurology Moscow Health Department"

Moscow, Russian Federation, 119602

Federal State Autonomous Institution "Scientific Center of Children's Health" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation, 119991

Federal State Budget Educational Institution of Higher Professional Learning "Stavropol State Medical University" of the Ministry of Health of the Russian Federation

Stavropol, Russian Federation, 355017

Sponsors and Collaborators

Merz Pharmaceuticals GmbH

LLC Merz Pharma, Russia

Investigators

• Study Director: Merz Medical Expert; LLC Merz Pharma, Russia

More Information

• Responsible Party: Merz Pharmaceuticals GmbH
• ClinicalTrials.gov Identifier: NCT02188277
• Other Study ID Numbers: MRZ-R-201212_01001_N_2
• First Posted: July 11, 2014
• Last Update Posted: January 26, 2017
• Last Verified: January 2017

Additional relevant MeSH terms:

Muscle Spasticity; Clubfoot; Talipes; Equinus Deformity; Cerebral Palsy; Paresis; Paraplegia; Paralysis; Neurologic Manifestations; Nervous System Diseases; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Foot Deformities, Acquired; Foot Deformities; Foot Deformities, Congenital; Lower Extremity Deformities, Congenital; Limb Deformities, Congenital; Musculoskeletal Abnormalities; Congenital Abnormalities; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; incobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators