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
Cerebral Palsy · Spasticity
Bottom Line
View on ClinicalTrials.gov: NCT02002884 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- IncobotulinumtoxinA (8 Units per kg body weight) (Drug); IncobotulinumtoxinA (6 Units per kg body weight) (Drug); IncobotulinumtoxinA (2 Units per kg body weight) (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Merz Pharmaceuticals GmbH
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4 |
-0.93; -1.15; -0.96; -1.02 | = 0.017 sig |
| PRIMARY Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4 |
1.55; 1.64; 1.57; 1.44 | = 0.34 |
| SECONDARY MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4 |
-1.03; -1.13; -1.08; -1.22 | — |
| SECONDARY MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4 |
-0.53; -1.00; -0.070; -1.04 | — |
| SECONDARY MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4 |
-0.99; -1.18; -1.01; -1.17; -0.96; -1.08 | — |
| SECONDARY MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)' |
-0.42; -0.75; -0.39; -0.67; -0.52; -0.64 | — |
| SECONDARY MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4 |
1.51; 1.63; 1.53; 1.48; 1.41; 1.60 | — |
| SECONDARY Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle |
21; 13; 42; 114; 21; 13 | — |
| SECONDARY Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle |
1; 1; 1; 5; 1; 1 | — |
| SECONDARY Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle |
2; 1; 2; 16; 2; 1 | — |
| SECONDARY Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle |
0; 0; 3; 5; 0; 0 | — |
| SECONDARY Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle |
15; 10; 33; 62; 6; 2 | — |
| SECONDARY Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle |
0; 0; 3; 5; 21; 13 | — |
| SECONDARY Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle |
18; 10; 39; 96; 1; 0 | — |
| SECONDARY Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle |
0; 1; 1; 5; 0; 1 | — |
Summary
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:
- Flexed elbow: AS≥2 in elbow flexors (at least unilaterally). and/or
- 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:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- 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:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- 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:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- 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:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- 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:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- 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 clinical
Data sourced from ClinicalTrials.gov (NCT02002884). 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.