Long-term Open-label Study of Botulinumtoxin Type A to Treat Spasticity of Leg(s) or Leg(s) and Arm in Cerebral Palsy
Condition: Lower Limb and Combined Lower Limb and Upper Limb Spasticity Due to Cerebral Palsy
MeSH terms: Muscle Spasticity; Cerebral Palsy
Intervention: IncobotulinumtoxinA (16-20 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); Total dose per injection cycle: up to 500 units; 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 370.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether injections of Botulinum toxin type A into
      muscles of the leg(s) or of leg(s) and one arm are safe in treating children/adolescents (age
      2-17 years) long-term with increased muscle tension/uncontrollable muscle stiffness
      (spasticity) due to cerebral palsy.
    

Eligibility criteria:

        Inclusion Criteria:

        Main clinical inclusion criteria for completers of study MRZ60201_3070_1:

          -  Subject with lower limb [LL] spasticity who completed lead-in study MRZ60201_3070_1 in
             any of the three dose groups with duration of both injection cycles between 12 and 16
             weeks.

          -  Ashworth scale [AS] score ≥2 in plantar flexors (at least unilaterally). For subjects
             with an AS score of 1, the investigator has to decide on the clinical need for
             reinjection.

          -  Clinical need for spasticity treatment with NT 201 according to the clinical judgment
             of the investigator for:

        Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes
        equinus and need for additional 8 U/kg BW NT 201 (maximum of 200 U) for treatment of
        clinical pattern flexed knee or adducted thigh (ipsilateral) or bilateral treatment of LL
        spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus on each side.

        No treatment of other clinical patterns is allowed.

        Main clinical inclusion criteria for subjects who did not participate in MRZ60201_3070_1:

          -  Female or male subject of 2 to 17 years age (inclusive).

          -  Uni- or bilateral CP with clinical need for BoNT injection to treat limb spasticity.

          -  AS score ≥ 2 in plantar flexors (at least unilaterally).

          -  Clinical need according to the clinical judgment of the investigator in one out of
             four treatment combinations:

               1. For LL(s) treatment only (Gross Motor Function Classification System [GMFCS]
                  levels IV): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum
                  of 200 U) into pes equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed
                  knee or adducted thigh or bilateral treatment of LL spasticity with 8 U/kg BW NT
                  201 (maximum of 200 U) into each pes equinus (AS score ≥ 2 on both sides).

               2. For combined unilateral UL and unilateral LL, (GMFCS levels I-III): Unilateral
                  treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes
                  equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed knee or adducted
                  thigh plus Unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum
                  of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or
                  pronated forearm.

               3. For combined unilateral UL and unilateral LL (GMFCS level IV-V): Unilateral
                  treatment of LL spasticity with 8 U/kg BW NT 201 (maximum 200 U) into pes
                  equinus, and 4 U/kg BW NT201 (maximum 100 U) into flexed knee or adducted thigh
                  plus unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100
                  U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated
                  forearm.

               4. For combined unilateral UL and bilateral LL (GMFCS levels I-III): Bilateral
                  treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into each pes
                  equinus (AS score ≥ 2 on both sides) plus unilateral treatment of UL spasticity
                  with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist,
                  clenched fist, thumb in palm and/or pronated forearm.

        Exclusion Criteria:

        Exclusion Criteria for subjects who completed MRZ60201_3070_1:

          -  Infection and/or inflammation in the area of the planned injection points.

          -  Pregnancy for female with history of menarche.

          -  Clinically relevant pathological findings indicating active disease of vital organs.

        Exclusion Criteria for subjects who did not participate in MRZ60201_3070_1:

          -  Fixed contracture defined as severe restriction of the range of joint movement on
             passive stretch in the target clinical pattern(s) or predominant forms of muscle
             hypertonia other than spasticity (e.g., dystonia) in the target limb(s).

          -  Surgery in the pes equinus on side(s) intended to treat with BoNT injections within 12
             months prior to Screening Visit (V1), within the screening period or planned for the
             time of participation in this study.

          -  Hip flexion requiring BoNT injection.

          -  Limitation of hip abduction to less than 40° or pre-diagnosed migrational percentage
             greater than 30.

          -  Vaccination within 2 weeks prior to Screening Visit (V1) and/or within the screening
             period.

          -  Non-resolved fractures of the treated limb.

          -  Ventilator dependency.

          -  Severe neurological diagnosis and comorbidity outside the spectrum of cerebral palsy.

          -  Pure dyskinetic CP or mixed CP with predominantly dyskinetic movements.

          -  Treatment with BoNT (other than study drug in this study) for any body region within
             14 weeks prior to Screening Visit (V1), within the screening period and/or intended to
             be administered during the study period.

          -  Treatment with phenol or alcohol of any muscle within 6 months prior to Screening
             Visit (V1), within the screening period, and/or intended to be administered during the
             study period.

          -  Treatment with

               -  drugs acting as peripheral muscle relaxants

               -  intrathecal baclofen, or

               -  oral anticoagulants administered within 2 weeks prior to Screening Visit (V1),
                  within the screening period, and/or intended to be administered during the study
                  period.