search
Back to results

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)

Primary Purpose

Cerebral Palsy, Spasticity

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
IncobotulinumtoxinA (8 Units per kg body weight)
IncobotulinumtoxinA (6 Units per kg body weight)
IncobotulinumtoxinA (2 Units per kg body weight)
Sponsored by
Merz Pharmaceuticals GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cerebral Palsy focused on measuring Upper limb spasticity, lower limb spasticity, combined upper and lower limb spasticity

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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 14 weeks prior to Screening Visit (V1) in any indication.

Sites / Locations

  • Merz Investigational Site #001286
  • Merz Investigational Site #001284
  • Merz Investigational Site #001285
  • Merz Investigational Site #001186
  • Merz Investigational Site No. #001302
  • Merz Investigational Site #001283
  • Merz Investigational Site #054010
  • Merz Investigational Site #054005
  • Merz Investigational Site #052023
  • Merz Investigational Site #052003
  • Merz Investigational Site #052024
  • Merz Investigational Site #052022
  • Merz Investigational Site #052027
  • Merz Investigational Site #052028
  • Merz Investigational Site #052026
  • Merz Investigational Site #048089
  • Merz Investigational Site #048063
  • Merz Investigational Site #048059
  • Merz Investigational Site #048084
  • Merz Investigational Site #048094
  • Merz Investigational Site #048075
  • Merz Investigational Site #048060
  • Merz Investigational Site #007014
  • Merz Investigational Site #007015
  • Merz Investigational Site #007018
  • Merz Investigational Site #007298
  • Merz Investigational Site #007013
  • Merz Investigational Site #007019
  • Merz Investigational Site #380001
  • Merz Investigational Site #380005
  • Merz Investigational Site #380002
  • Merz Investigational Site #380003

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

8 Units per kg body weight incobotulinumtoxinA (Xeomin)

6 Units per kg body weight incobotulinumtoxinA (Xeomin)

2 Units per kg body weight incobotulinumtoxinA (Xeomin)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4
The AS categorizes severity of spasticity by judging resistance to passive movement. Spasticity was assessed by using the 5-point AS with:0 (no increase in tone); 1 (slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2 (more marked increase in tone, but limb easily flexed); 3 (considerable increase in tone -passive movements difficult); 4 (limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and Week 4 resulting from Mixed Model Repeated Measurement (MMRM) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4
The GICS was used to measure independently the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.

Secondary Outcome Measures

MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with QPS. The QPS Total Score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS Total Score for the observed pain frequency ranges from 0 (Never) to 4 (Always). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. P/C = Parent/Caregiver.
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
The GICS was used to measure independently the child's/adolescent's, and parent's or caregiver's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from: +3(very much improved); +2(much improved); +1(minimally improved); 0(no change); -1(minimally worse); -2(much worse); -3(very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle

Full Information

First Posted
December 2, 2013
Last Updated
August 3, 2021
Sponsor
Merz Pharmaceuticals GmbH
search

1. Study Identification

Unique Protocol Identification Number
NCT02002884
Brief Title
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
Acronym
XARA
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
March 28, 2014 (Actual)
Primary Completion Date
July 4, 2017 (Actual)
Study Completion Date
August 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merz Pharmaceuticals GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Palsy, Spasticity
Keywords
Upper limb spasticity, lower limb spasticity, combined upper and lower limb spasticity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
351 (Actual)

8. Arms, Groups, and Interventions

Arm Title
8 Units per kg body weight incobotulinumtoxinA (Xeomin)
Arm Type
Experimental
Arm Description
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.
Arm Title
6 Units per kg body weight incobotulinumtoxinA (Xeomin)
Arm Type
Experimental
Arm Description
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.
Arm Title
2 Units per kg body weight incobotulinumtoxinA (Xeomin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IncobotulinumtoxinA (8 Units per kg body weight)
Other Intervention Name(s)
Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Intervention 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); Mode of administration: intramuscular injection into spastic muscles.
Intervention Type
Drug
Intervention Name(s)
IncobotulinumtoxinA (6 Units per kg body weight)
Other Intervention Name(s)
Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Intervention 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); Mode of administration: intramuscular injection into spastic muscles.
Intervention Type
Drug
Intervention Name(s)
IncobotulinumtoxinA (2 Units per kg body weight)
Other Intervention Name(s)
Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Intervention 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); Mode of administration: intramuscular injection into spastic muscles.
Primary Outcome Measure Information:
Title
MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4
Description
The AS categorizes severity of spasticity by judging resistance to passive movement. Spasticity was assessed by using the 5-point AS with:0 (no increase in tone); 1 (slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2 (more marked increase in tone, but limb easily flexed); 3 (considerable increase in tone -passive movements difficult); 4 (limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and Week 4 resulting from Mixed Model Repeated Measurement (MMRM) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time Frame
Baseline and Week 4
Title
Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4
Description
The GICS was used to measure independently the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4
Description
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time Frame
Baseline and Week 4
Title
MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4
Description
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time Frame
Baseline and Week 4
Title
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Description
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time Frame
Baseline up to Week 4
Title
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
Description
Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with QPS. The QPS Total Score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS Total Score for the observed pain frequency ranges from 0 (Never) to 4 (Always). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. P/C = Parent/Caregiver.
Time Frame
Baseline, Weeks 4, 8, and 14
Title
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
Description
The GICS was used to measure independently the child's/adolescent's, and parent's or caregiver's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from: +3(very much improved); +2(much improved); +1(minimally improved); 0(no change); -1(minimally worse); -2(much worse); -3(very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time Frame
Week 4
Title
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66
Title
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66
Title
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66
Title
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66
Title
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66
Title
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66
Title
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66
Title
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Time Frame
Baseline up to Week 66

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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: Flexed elbow: AS≥2 in elbow flexors (at least unilaterally). and/or 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: At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW). and 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: At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW). and 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: At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW). and 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: At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW). and 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: At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW). and 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 At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW) and 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 14 weeks prior to Screening Visit (V1) in any indication.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merz Medical Expert
Organizational Affiliation
Merz Pharmaceuticals GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Merz Investigational Site #001286
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Merz Investigational Site #001284
City
Loxahatchee Groves
State/Province
Florida
ZIP/Postal Code
33470
Country
United States
Facility Name
Merz Investigational Site #001285
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31405
Country
United States
Facility Name
Merz Investigational Site #001186
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Merz Investigational Site No. #001302
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Merz Investigational Site #001283
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Merz Investigational Site #054010
City
Godoy Cruz
State/Province
Provincia De Mendoza
ZIP/Postal Code
M5501
Country
Argentina
Facility Name
Merz Investigational Site #054005
City
Caba
ZIP/Postal Code
CP 1428
Country
Argentina
Facility Name
Merz Investigational Site #052023
City
Aguascalientes
ZIP/Postal Code
20127
Country
Mexico
Facility Name
Merz Investigational Site #052003
City
Guadalajara
ZIP/Postal Code
44280
Country
Mexico
Facility Name
Merz Investigational Site #052024
City
Mexico City
ZIP/Postal Code
04530
Country
Mexico
Facility Name
Merz Investigational Site #052022
City
Mexico City
ZIP/Postal Code
06700
Country
Mexico
Facility Name
Merz Investigational Site #052027
City
Monterrey
ZIP/Postal Code
64060
Country
Mexico
Facility Name
Merz Investigational Site #052028
City
Monterrey
ZIP/Postal Code
64710
Country
Mexico
Facility Name
Merz Investigational Site #052026
City
Zapopan
ZIP/Postal Code
45030
Country
Mexico
Facility Name
Merz Investigational Site #048089
City
Bialystok
ZIP/Postal Code
15-274
Country
Poland
Facility Name
Merz Investigational Site #048063
City
Gdansk
ZIP/Postal Code
80-389
Country
Poland
Facility Name
Merz Investigational Site #048059
City
Krakow
ZIP/Postal Code
30-539
Country
Poland
Facility Name
Merz Investigational Site #048084
City
Lublin
ZIP/Postal Code
20-828
Country
Poland
Facility Name
Merz Investigational Site #048094
City
Poznan
ZIP/Postal Code
60-480
Country
Poland
Facility Name
Merz Investigational Site #048075
City
Sandomierz
ZIP/Postal Code
27-600
Country
Poland
Facility Name
Merz Investigational Site #048060
City
Wiazowna
ZIP/Postal Code
05-462
Country
Poland
Facility Name
Merz Investigational Site #007014
City
Kazan
ZIP/Postal Code
420097
Country
Russian Federation
Facility Name
Merz Investigational Site #007015
City
Khabarovsk
ZIP/Postal Code
680038
Country
Russian Federation
Facility Name
Merz Investigational Site #007018
City
Novosibirsk
ZIP/Postal Code
630091
Country
Russian Federation
Facility Name
Merz Investigational Site #007298
City
Saint Petersburg
ZIP/Postal Code
192148
Country
Russian Federation
Facility Name
Merz Investigational Site #007013
City
Smolensk
ZIP/Postal Code
214019
Country
Russian Federation
Facility Name
Merz Investigational Site #007019
City
Stavropol
ZIP/Postal Code
355029
Country
Russian Federation
Facility Name
Merz Investigational Site #380001
City
Dnipropetrovsk
ZIP/Postal Code
49000
Country
Ukraine
Facility Name
Merz Investigational Site #380005
City
Kharkiv
ZIP/Postal Code
61068
Country
Ukraine
Facility Name
Merz Investigational Site #380002
City
Kyiv
ZIP/Postal Code
04209
Country
Ukraine
Facility Name
Merz Investigational Site #380003
City
Odessa
ZIP/Postal Code
65012
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34339951
Citation
Dabrowski E, Chambers HG, Gaebler-Spira D, Banach M, Kanovsky P, Dersch H, Althaus M, Geister TL, Heinen F. IncobotulinumtoxinA Efficacy/Safety in Upper-Limb Spasticity in Pediatric Cerebral Palsy: Randomized Controlled Trial. Pediatr Neurol. 2021 Oct;123:10-20. doi: 10.1016/j.pediatrneurol.2021.05.014. Epub 2021 May 21.
Results Reference
result
PubMed Identifier
36136523
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs