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
Condition: Cerebral Palsy; Spasticity
MeSH terms: Muscle Spasticity; Cerebral Palsy
Intervention: IncobotulinumtoxinA (8 Units per kg body weight); IncobotulinumtoxinA (6 Units per kg body weight); IncobotulinumtoxinA (2 Units per kg body weight)
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.; 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.; 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 MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; incobotulinumtoxinA
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 351.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Upper limb spasticity; lower limb spasticity; combined upper and lower limb spasticity

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.
    

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:

               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.