Overview

This trial is active, not recruiting.

Condition lower limb and combined lower limb and upper limb spasticity due to cerebral palsy
Treatment incobotulinumtoxina (16-20 units per kg body weight)
Phase phase 3
Sponsor Merz Pharmaceuticals GmbH
Start date August 2013
End date January 2017
Trial size 370 participants
Trial identifier NCT01905683, 2012-005055-17, MRZ60201_3071_1

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
incobotulinumtoxina (16-20 units per kg body weight) Xeomin
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.

Primary Outcomes

Measure
Occurrence of treatment emergent adverse events [TEAEs], AEs of special interest [TEAESIs], and serious AEs [TESAEs], overall and per injection cycle
time frame: Baseline up to week 56

Secondary Outcomes

Measure
Investigator's Global Assessment of Tolerability at Injection Visits and at End of Study Visit at day 99 (week 14) for the respective past injection cycle.
time frame: Week 14 up to week 56
Changes in the AS score of plantar flexors from baseline (Day 1) to all other visits and from Day 1 of each injection cycle to Control Visit at Day 29 (Week 4), Day 57 (Week 8, only 1st cycle), and Day 99 (Week 14) of the respective injection cycle
time frame: Baseline up to week 56
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.
time frame: Week 4 up to week 46
Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale [GICS-PF] at Day 29 (Week 4) of each respective injection cycle.
time frame: Week 4 up to week 46
Changes from baseline (Day 1) 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.
time frame: Baseline up to week 56
Changes from baseline in scores of pain intensity and frequency assessed with Questionnaire on Pain caused by Spasticity [QPS] to all post baseline visits of the respective injection cycle
time frame: Baseline up to week 56
Changes in GMFM-66 score from the 1st Injection Visit (Day 1) to all injection visits of the subsequent injection cycles and to the End of Study Visit.
time frame: Baseline up to week 56

Eligibility Criteria

Male or female participants from 2 years up to 17 years old.

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.

Additional Information

Official title Open-label, Non-controlled, Multicenter Long-term Study to Investigate the Safety and Efficacy of Xeomin® (Incobotulinumtoxin A, NT 201) for the Treatment of Spasticity of the Lower Limb(s) or of Combined Spasticity of Upper and Lower Limb in Children and Adolescents (Age 2 - 17 Years) With Cerebral Palsy
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Merz Pharmaceuticals GmbH.