Phase 3
N=370
Long-term Open-label Study of Botulinumtoxin Type A to Treat Spasticity of Leg(s) or Leg(s) and Arm in Cerebral Palsy
Lower Limb and Combined Lower Limb and Upper Limb Spasticity Due to Cerebral Palsy
Bottom Line
View on ClinicalTrials.gov: NCT01905683 ↗Enrolled (actual)
370
Serious AEs
4.3%
Results posted
Oct 2017
Primary outcome: Primary: Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle — 53; 44; 26; 31 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- IncobotulinumtoxinA (16-20 Units per kg body weight) (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Merz Pharmaceuticals GmbH
- Primary completion
- Jan 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle |
53; 44; 26; 31; 109 | — |
| PRIMARY Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle |
1; 2; 1; 0; 3 | — |
| PRIMARY Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle |
6; 5; 5; 1; 16 | — |
| SECONDARY Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle |
203; 119; 23; 5; 225; 87 | — |
| SECONDARY Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle |
-0.8; -0.7; -0.2; -1.1; -0.3; -1.2 | — |
| SECONDARY Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle |
1.7; 1.8; 1.9; 2; 1.6; 1.7 | — |
| SECONDARY Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle |
1.7; 1.8; 1.9; 2; 1.7; 1.8 | — |
| SECONDARY Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle |
-1.4; -1.8; -1; -1; -1.7; -0.5 | — |
| SECONDARY Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection |
-0.6; -0.5; -0.5; -0.9; -0.7; -1.1 | — |
| SECONDARY Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study |
1.5; 2.6; 3.8; 4.8 | — |
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:
- 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).
- 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.
- 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.
- 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
Data sourced from ClinicalTrials.gov (NCT01905683). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.