Lower limb and combined lower limb and upper limb spasticity due to cerebral palsy MedDRA version: 18.0 Level: LLT Classification code 10058977 Term: Spastic paresis System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Xeomin
Product Name: NT 201
Product Code: NT 201
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: n.a
Current Sponsor code: NT 101
Other descriptive name: CLOSTR
Sponsors
Merz Pharmaceuticals GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main clinical inclusion criteria for completers of study MRZ60201_3070_1: • Subject with 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 (GMFCS levels I V): 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. Are the trial subjects under 18? yes Number of subjects for this age range: 360 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 IP 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: n.a;Primary end point(s): Occurrence of treatment emergent adverse events [TEAEs], AEs of special interest [TEAESIs], and serious AEs [TESAEs], overall and per injection cycle. ;Timepoint(s) of evaluation of this end point: Overall and per injection cycle 1-4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Investigator’s Global Assessment of Tolerability at Injection Visits (V5, V7, and V9) and at End of Study Visit (V11) at Day 99 (Week 14) of each injection cycle. • Changes in the AS score of plantar flexors from baseline (Day 1, V2) to all other visits and from Day 1 of each injection cycle to Control [Ctrl.] Visit at Day 29 (Week 4), Day 57 (Week 8, only 1st cycle), and Day 99 (Week 14) of the respective injection cycle. • Investigator’s, Child’s/Adolescent’s and Parent’s/Caregiver’s Global Impression of Change Scale [GICS] at Day 29 (Week 4) of all injection cycles. • Investigator’s Global Impression of Change of Planter Flexor Spasticity Scale [GICS PF] at Day 29 (Week 4) of each respective injection cycle. • Changes from baseline (Day 1, V2) of modified Tardieu Scale [MTS] of plantar flexors to all other visits and from Day 1 of each injection cycle to Day 29 (Week 4), Day 57 (Week 8, only 1st cycle), and Day 99 (Week 14) of the respective injection cycle. • Changes from baseline (Day 1, V2) in scores of pain intensity (from subject) and pain frequency (from parent/caregiver) assessed with Questionnaire on Pain caused by Spasticity for subjects with CP [QPS] to all other visits and from Day 1 of each injection cycle to Day 29 (Week 4), Day 57 (Week 8, only 1st cycle), and Day 99 (Week 14) of the respective injection cycle. • Changes in GMFM-66 score from the 1st Injection Visit (Day 1, V2) to all injection visits of the subsequent injection cycles (V5, V7 and V9) and to the End of Study Visit V11.;Timepoint(s) of evaluation of this end point: Between week4 and week 14 of each injection cycle | — |
Countries
Australia, Austria, Czech Republic, Estonia, Germany, Israel, Korea, Republic of, New Zealand, Poland, Romania, Russian Federation, Slovakia, Spain, Turkey, Ukraine
Outcome results
None listed