Trial record 5 of 63 for:    Open Studies | "Muscle Spasticity"

Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy (XARA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Merz Pharmaceuticals GmbH
Sponsor:
Information provided by (Responsible Party):
Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:
NCT02002884
First received: December 2, 2013
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of one or both arms alone or in combination with injections into one or both legs are effective and safe in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.


Condition Intervention Phase
Cerebral Palsy
Spasticity
Drug: IncobotulinumtoxinA (8 Units per kg body weight)
Drug: IncobotulinumtoxinA (6 Units per kg body weight)
Drug: IncobotulinumtoxinA (2 Units per kg body weight)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Multicenter, Randomized, Double-blind, Parallel-group, Dose-response Study of Three Doses Xeomin® (incobotulinumtoxinA, NT 201) for the Treatment of Upper Limb Spasticity Alone or Combined Upper and Lower Limb Spasticity in Children and Adolescents (Age 2 - 17 Years) With Cerebral Palsy

Resource links provided by NLM:


Further study details as provided by Merz Pharmaceuticals GmbH:

Primary Outcome Measures:
  • Change from baseline in Ashworth Scale (AS) in the primary clinical target pattern, i.e. elbow flexors or wrist flexors [ Time Frame: Baseline to week 4 ] [ Designated as safety issue: No ]
    Primary clinical target pattern is defined by the investigator. 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).

  • Investigator's Global Impression of Change Scale (GICS) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    This is a co-primary outcome measure. The GICS is used to measure the investigator's impression of change due to treatment. The response option is a common 7-point Likert scale that ranges from -3 = very much worse to +3 = very much improved.


Secondary Outcome Measures:
  • Change from baseline in AS score of the other treated main clinical target pattern (i.e. of elbow flexors or wrist flexors, if treated) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    This analysis will be performed in case two target patterns would qualify as main clinical target pattern for the main clinical target pattern not analyzed as primary efficacy variable.

  • Change from baseline in AS score of treated clinical target pattern clenched fist [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    In subjects treated in combination with flexed wrist.

  • Change from baseline in AS score for each treated clinical pattern (e.g., flexed elbow, flexed wrist, clenched fist, etc.) of the upper limb at all other post baseline visits of main period [ Time Frame: Baseline up to week 14 ] [ Designated as safety issue: No ]
  • Change from baseline in scores of pain intensity (from subjects) and pain frequency (from parent/caregiver) at all other post baseline visits of main period [ Time Frame: Baseline up to week 14 ] [ Designated as safety issue: No ]
    Assessed with 'Questionnaire on Pain caused by Spasticity (QPS)'.

  • Child's/Adolescent's GICS (if applicable) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Parent's/Caregiver's GICS [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

Estimated Enrollment: 344
Study Start Date: February 2014
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 8 Units per kg body weight incobotulinumtoxinA (Xeomin)
8 Units per kg body weight (maximum of 200 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 300 Units per injection cycle. Overall maximum dose per injection cycle: 500 Units.
Drug: IncobotulinumtoxinA (8 Units per kg body weight)
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); Mode of administration: intramuscular injection into spastic muscles.
Other Names:
  • Xeomin
  • NT 201
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Experimental: 6 Units per kg body weight incobotulinumtoxinA (Xeomin)
6 Units per kg body weight (maximum of 150 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 225 Units per injection cycle. Overall maximum dose per injection cycle: 375 Units.
Drug: IncobotulinumtoxinA (6 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% odium Chloride (NaCl); Mode of administration: intramuscular injection into spastic muscles.
Other Names:
  • Xeomin
  • NT 201
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Experimental: 2 Units per kg body weight incobotulinumtoxinA (Xeomin)
2 Units per kg body weight (maximum of 50 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 75 Units per injection cycle. Overall maximum dose per injection cycle: 125 Units.
Drug: IncobotulinumtoxinA (2 Units per kg body weight)
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); Mode of administration: intramuscular injection into spastic muscles.
Other Names:
  • Xeomin
  • NT 201
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female or male subject of 2 to 17 years of age (inclusive).
  • Uni- or bilateral Cerebral Palsy (CP) with clinical need for injections with NT 201 for the treatment of upper limb (UL) spasticity at least unilaterally.
  • Ashworth Scale (AS) score in the main clinical target patterns in this study:

    1. Flexed elbow: AS≥2 in elbow flexors (at least unilaterally). and/or
    2. Flexed Wrist: AS≥2 in wrist flexors (at least unilaterally).
  • Clinical need according to the judgment of the investigator in one out of five treatment combinations (A-E, as shown below). AS score must be ≥2 for each target pattern chosen for injection at the Baseline Injection Visit V2.

A. UL(s) treatment only (GMFCS I-V):

A1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:

  1. At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).

    and

  2. Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.

or

A2) Bilateral treatment of UL spasticity with equal doses of 8 U/kg BW NT 201 (maximum of 200 U) to each UL. Dose per UL must be distributed between:

  1. At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).

    and

  2. Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.

B. Unilateral UL and unilateral lower limb (LL) treatment (GMFCS I-V):

B1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:

  1. At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).

    and

  2. Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.

plus

B2) Ipsilateral unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U). Dose to LL must be distributed to at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe as clinically needed.

C. Unilateral UL and bilateral LL treatment (GMFCS I-III)

C1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:

  1. At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).

    and

  2. Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.

plus

C2) Bilateral treatment of LL spasticity with 12 U/kg BW (maximum of 300 U). Dose must be distributed into at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe, on each side. Dose distribution may vary between sides as clinically needed.

D. Unilateral UL and bilateral LL treatment (GMFCS IV and V)

D1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:

  1. At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).

    and

  2. Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.

plus

D2) Bilateral treatment of LL spasticity with 8 U/kg BW (maximum of 200 U). Dose must be distributed into at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe, on each side. Dose distribution may vary between sides as clinically needed.

E. Bilateral UL treatment and bilateral LL treatment (GMFCS I-III)

E1) Bilateral treatment of UL spasticity with equal doses of 8 U/kg BW NT 201 (maximum of 200 U) to each UL. Dose per UL must be distributed between

  1. at least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW) and
  2. additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.

plus

E2) Bilateral treatment of LL spasticity with 4 U/kg BW (maximum of 100 U). Dose must be distributed into at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe, on each side. Dose distribution may vary between sides as clinically needed.

Exclusion Criteria:

Pre-treated (non-naïve) subjects must not have received BoNT treatment within the last 16 weeks prior to study treatment at V2 in any indication.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02002884

Contacts
Contact: Public Disclosure Manager clinicaltrials@merz.de

Locations
United States, California
Merz Investigational Site #001281 Recruiting
San Diego, California, United States, 92123-4282
United States, Florida
Merz Investigational Site #001286 Recruiting
Gulf Breeze, Florida, United States, 32561
Merz Investgational Site #001284 Recruiting
Wellington, Florida, United States, 33414
United States, Georgia
Merz Investigational Site #001285 Recruiting
Savannah, Georgia, United States, 31405
United States, Illinois
Merz Investigational Site #001186 Recruiting
Chicago, Illinois, United States, 60611
United States, Michigan
Merz Investigational Site No. #001302 Recruiting
Royal Oak, Michigan, United States, 48073
United States, Missouri
Merz Investigational Site #001283 Recruiting
Columbia, Missouri, United States, 65212
Sponsors and Collaborators
Merz Pharmaceuticals GmbH
Investigators
Study Director: Merz Medical Expert Merz Pharmaceuticals GmbH
  More Information

No publications provided

Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT02002884     History of Changes
Other Study ID Numbers: MRZ60201_3072_1
Study First Received: December 2, 2013
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Federal Commission for Protection Against Health Risks

Keywords provided by Merz Pharmaceuticals GmbH:
Upper limb spasticity
lower limb spasticity
combined upper and lower limb spasticity

Additional relevant MeSH terms:
Muscle Spasticity
Cerebral Palsy
Brain Damage, Chronic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Botulinum Toxins
Botulinum Toxins, Type A
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014