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)
Cerebral Palsy, Spasticity
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
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.
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
Experimental
Experimental
Experimental
8 Units per kg body weight incobotulinumtoxinA (Xeomin)
6 Units per kg body weight incobotulinumtoxinA (Xeomin)
2 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.
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.