<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02188277</url>
  </required_header>
  <id_info>
    <org_study_id>MRZ-R-201212_01001_N_2</org_study_id>
    <nct_id>NCT02188277</nct_id>
  </id_info>
  <brief_title>Treatment With Xeomin Versus Botox in Children With Spastic Equine and Equinovarus Foot Deformation in Pediatric Cerebral Palsy</brief_title>
  <acronym>XEBEC</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merz Pharmaceuticals GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>LLC Merz Pharma, Russia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Merz Pharmaceuticals GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      1. To assess the clinical and neurophysiological efficacy of Xeomin® vs. Botox® in children&#xD;
           with spastic equine and equinovarus foot deformation in pediatric cerebral palsy&#xD;
&#xD;
        2. To assess the safety of Xeomin® use as compared to Botox® in this patient population&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale (AS)</measure>
    <time_frame>From baseline to day 30</time_frame>
    <description>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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in patient percentage in groups by the degree of gastrocnemius spasticity according to modified Ashworth scale</measure>
    <time_frame>From baseline up to day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of decrease in M-response magnitude and area recorded from the lateral and medial gastrocnemius heads, from baseline values</measure>
    <time_frame>From baseline up to day 90</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in the ratio of M-response recorded from the lateral and medial gastrocnemius heads and from tibialis anterior</measure>
    <time_frame>From baseline up to day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in angles and angle ratio of ankle joints at passive and voluntary extension</measure>
    <time_frame>From baseline up to day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in motor activity according to Gross Motor Function Classification Systems (GMFCS) criteria</measure>
    <time_frame>From baseline up to day 90</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale</measure>
    <time_frame>Baseline up to day 90</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Cerebral Palsy</condition>
  <condition>Spastic Paraplegia and Hemiparesis</condition>
  <condition>Equine and Equinovarus Foot Deformation</condition>
  <arm_group>
    <arm_group_label>Xeomin®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4-8 Units per kg body weight. Single injection cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Botox®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4-6(8) Units per kg body weight. Single injection cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Xeomin</intervention_name>
    <description>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).&#xD;
Administration route is intramuscular injection into medial (two points) and lateral heads (two points) of gastrocnemius.</description>
    <arm_group_label>Xeomin®</arm_group_label>
    <other_name>IncobotulinumtoxinA</other_name>
    <other_name>NT 201</other_name>
    <other_name>Botulinum toxin type A (150 kiloDalton), free from complexing proteins</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Botox®</intervention_name>
    <description>Administration route is intramuscular injection into medial (two points) and lateral heads (two points) of gastrocnemius.</description>
    <arm_group_label>Botox®</arm_group_label>
    <other_name>OnabotulinumtoxinA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children from 2 through 12 years of age, of both sexes, suffering from spastic&#xD;
             paraplegia or hemiparesis in pediatric cerebral palsy.&#xD;
&#xD;
          -  Equine and equinovarus foot posture.&#xD;
&#xD;
          -  Gastrocnemius spasticity of 2 points and greater, by modified Ashworth scale.&#xD;
&#xD;
          -  Patient can walk unassisted or with a support.&#xD;
&#xD;
          -  Mental development of patients is normal or mildly retarded.&#xD;
&#xD;
          -  Previous course of spasticity treatment with BTA products was completed earlier than&#xD;
             at 6 months before this trial or never administered before.&#xD;
&#xD;
          -  Patient's parents have signed an informed consent, are able and wishing to adhere to&#xD;
             procedures described in the trial protocol and to the schedule of visits throughout&#xD;
             the entire period of treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fixed ankle joint contracture.&#xD;
&#xD;
          -  Previous denervation of spastic muscles by surgery, phenol or alcohol;&#xD;
&#xD;
          -  Athetosis and dystonia in the area of injected muscles.&#xD;
&#xD;
          -  Inflammation at the planned injection site.&#xD;
&#xD;
          -  Elevated body temperature and acute (infectious and non-infectious) diseases at the&#xD;
             time of injection.&#xD;
&#xD;
          -  Neuromuscular transmission disorders (myasthenia gravis, Lambert-Eaton syndrome,&#xD;
             etc.).&#xD;
&#xD;
          -  Decompensated physical diseases potentially affecting the trial findings.&#xD;
&#xD;
          -  Acute fever, infection or surgery within 1 month before the trial.&#xD;
&#xD;
          -  Use of aminoglycosides or spectinomycin within 1 month before starting the trial.&#xD;
&#xD;
          -  Hypersensitivity to any of product ingredients.&#xD;
&#xD;
          -  Positive history for allergies (especially with regard to protein-containing&#xD;
             products).&#xD;
&#xD;
          -  Patient's parents are unable or unwilling to adhere to the trial protocol requirements&#xD;
             including signing the informed consent and conforming to the schedule of visits.&#xD;
&#xD;
          -  Participation in other clinical trials in the last 4 weeks before inclusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Merz Medical Expert</last_name>
    <role>Study Director</role>
    <affiliation>LLC Merz Pharma, Russia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>State Budget Institution of Health in Moscow &quot;Scientific and Practical Center of Pediatric psychoneurology Moscow Health Department&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>119602</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Autonomous Institution &quot;Scientific Center of Children's Health&quot; of the Ministry of Health of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <zip>119991</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budget Educational Institution of Higher Professional Learning &quot;Stavropol State Medical University&quot; of the Ministry of Health of the Russian Federation</name>
      <address>
        <city>Stavropol</city>
        <zip>355017</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>January 25, 2017</last_update_submitted>
  <last_update_submitted_qc>January 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
    <mesh_term>Clubfoot</mesh_term>
    <mesh_term>Talipes</mesh_term>
    <mesh_term>Equinus Deformity</mesh_term>
    <mesh_term>Cerebral Palsy</mesh_term>
    <mesh_term>Paresis</mesh_term>
    <mesh_term>Paraplegia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
    <mesh_term>incobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02188277
org study id: MRZ-R-201212_01001_N_2
nct id: NCT02188277
lead sponsor: 
collaborator: 
has dmc: No
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale (AS)
time frame: From baseline to day 30
description: 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).
measure: 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
measure: 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
description: 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.
measure: 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
measure: Changes from baseline in angles and angle ratio of ankle joints at passive and voluntary extension
time frame: From baseline up to day 90
measure: Changes from baseline in motor activity according to Gross Motor Function Classification Systems (GMFCS) criteria
time frame: From baseline up to day 90
description: 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.
measure: Changes from baseline in the degree of spasticity in gastrocnemius according to modified Ashworth scale
time frame: Baseline up to day 90
arm group label: Xeomin®
arm group type: Experimental
description: 4-8 Units per kg body weight. Single injection cycle.
arm group label: Botox®
arm group type: Active Comparator
description: 4-6(8) Units per kg body weight. Single injection cycle.
intervention type: Drug
intervention name: Xeomin
description: 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.
arm group label: Xeomin®
other name: IncobotulinumtoxinA
other name: NT 201
other name: Botulinum toxin type A (150 kiloDalton), free from complexing proteins
intervention type: Drug
intervention name: Botox®
description: Administration route is intramuscular injection into medial (two points) and lateral heads (two points) of gastrocnemius.
arm group label: Botox®
other name: OnabotulinumtoxinA
criteria: 
gender: All
minimum age: 2 Years
maximum age: 12 Years
healthy volunteers: No
last name: Merz Medical Expert
role: Study Director
affiliation: LLC Merz Pharma, Russia
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Muscle Spasticity
mesh term: Clubfoot
mesh term: Talipes
mesh term: Equinus Deformity
mesh term: Cerebral Palsy
mesh term: Paresis
mesh term: Paraplegia
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
mesh term: incobotulinumtoxinA