CompletedNCT02002884XARAUpdated Aug 5, 2021Results posted

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

A Phase 3 interventional study of IncobotulinumtoxinA (8 Units per kg body weight) and IncobotulinumtoxinA (6 Units per kg body weight) in Cerebral Palsy and Spasticity, sponsored by Merz Pharmaceuticals GmbH. Completed at 32 sites in 6 countries. Open to participants aged 2 Years to 17 Years. Per ClinicalTrials.gov, last updated 2021-08-05.

Sponsored by Merz Pharmaceuticals GmbH · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 351
Allocation: Randomized
Ages: 2 Years to 17 Years
Sex: All

Study summary

The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of one or both arms alone or in combination with injections into one or both legs are effective and safe in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.

Conditions studied

Cerebral Palsy
Spasticity

Browse trials for

Keywords

Upper limb spasticity
lower limb spasticity
combined upper and lower limb spasticity

In context

Muscle Spasticity

704 studies on the registry are indexed under Muscle Spasticity; 149 are open to participants now.

This study's enrollment of 351 is above the median of 36 across 525 interventional studies indexed under Muscle Spasticity.

Browse Muscle Spasticity studies →

Lead sponsor

Merz Pharmaceuticals GmbH is the lead sponsor of 60 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 2 Years to 17 Years
Sexes eligible: All
Accepts healthy volunteers: No

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:
1. Flexed elbow: AS≥2 in elbow flexors (at least unilaterally). and/or
2. 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.

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 clinically needed.

E. Bilateral UL treatment and bilateral LL treatment (GMFCS I-III)

E1) 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.

plus

E2) Bilateral treatment of LL spasticity with 4 U/kg BW (maximum of 100 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.

Exclusion criteria

Exclusion Criteria:

Pre-treated (non-naïve) subjects must not have received BoNT treatment within the last 14 weeks prior to Screening Visit (V1) in any indication.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 351 participants (actual)

Study arms

Experimental
8 Units per kg body weight incobotulinumtoxinA (Xeomin)
8 Units per kg body weight (maximum of 200 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 300 Units per injection cycle. Overall maximum dose per injection cycle: 500 Units.
Drug: IncobotulinumtoxinA (8 Units per kg body weight)
Experimental
6 Units per kg body weight incobotulinumtoxinA (Xeomin)
6 Units per kg body weight (maximum of 150 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 225 Units per injection cycle. Overall maximum dose per injection cycle: 375 Units.
Drug: IncobotulinumtoxinA (6 Units per kg body weight)
Experimental
2 Units per kg body weight incobotulinumtoxinA (Xeomin)
2 Units per kg body weight (maximum of 50 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 75 Units per injection cycle. Overall maximum dose per injection cycle: 125 Units.
Drug: IncobotulinumtoxinA (2 Units per kg body weight)

Interventions

DrugIncobotulinumtoxinA (8 Units per kg body weight)
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); Mode of administration: intramuscular injection into spastic muscles.
Also known as: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
DrugIncobotulinumtoxinA (6 Units per kg body weight)
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); Mode of administration: intramuscular injection into spastic muscles.
Also known as: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
DrugIncobotulinumtoxinA (2 Units per kg body weight)
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); Mode of administration: intramuscular injection into spastic muscles.
Also known as: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins

What researchers measure

Primary outcomes

MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4
The AS categorizes severity of spasticity by judging resistance to passive movement. Spasticity was assessed by using the 5-point AS with:0 (no increase in tone); 1 (slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2 (more marked increase in tone, but limb easily flexed); 3 (considerable increase in tone -passive movements difficult); 4 (limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and Week 4 resulting from Mixed Model Repeated Measurement (MMRM) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline and Week 4
Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4
The GICS was used to measure independently the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Week 4

Secondary outcomes

MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline and Week 4
MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline and Week 4
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Baseline up to Week 4
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)'
Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with QPS. The QPS Total Score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS Total Score for the observed pain frequency ranges from 0 (Never) to 4 (Always). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. P/C = Parent/Caregiver.
Time frame: Baseline, Weeks 4, 8, and 14
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
The GICS was used to measure independently the child's/adolescent's, and parent's or caregiver's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from: +3(very much improved); +2(much improved); +1(minimally improved); 0(no change); -1(minimally worse); -2(much worse); -3(very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Time frame: Week 4
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Time frame: Baseline up to Week 66

Results

Posted Aug 3, 2020

Participant flow

The study was conducted at 28 investigative sites in Mexico, Argentina, Russian federation, Ukraine, United States and Poland.

Main Period (MP)

Participant flow — Main Period (MP)
Milestone	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
Started	87	88	176
Treated	87	87	176
Completed	81	82	168
Not completed	6	6	8
Withdrew: Other	0	3	3
Withdrew: Adverse event	0	1	1
Withdrew: Withdrawal by subject	6	2	2
Withdrew: Lost to follow-up	0	0	2

Open-Label Extension Period (OLEX)

Participant flow — Open-Label Extension Period (OLEX)
Milestone	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Started	0	0	0	331
Completed	0	0	0	281
Not completed	0	0	0	50
Withdrew: Other	0	0	0	24
Withdrew: Physician decision	0	0	0	1
Withdrew: Adverse event	0	0	0	5
Withdrew: Withdrawal by subject	0	0	0	10
Withdrew: Lost to follow-up	0	0	0	10

Outcome measures

PrimaryMP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4

The AS categorizes severity of spasticity by judging resistance to passive movement. Spasticity was assessed by using the 5-point AS with:0 (no increase in tone); 1 (slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2 (more marked increase in tone, but limb easily flexed); 3 (considerable increase in tone -passive movements difficult); 4 (limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and Week 4 resulting from Mixed Model Repeated Measurement (MMRM) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.

Time frame:: Baseline and Week 4
Reported as:: Least squares mean · Unit on a scale

MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4
Unit on a scale	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
High versus low	-0.93 ± 0.078	—	-1.15 ± 0.056
Mid versus low	-0.96 ± 0.082	-1.02 ± 0.082	—

Statistical analysis

MP Low Dose Group vs MP High Dose Group · MMRM · p = = 0.017 · Ls mean difference: -0.22 · 95% CI -0.4 to -0.04
MP Low Dose Group vs MP Mid Dose Group · MMRM · p = = 0.546 · Ls-mean difference: -0.07 · 95% CI -0.29 to 0.15

PrimaryCo-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4

The GICS was used to measure independently the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.

Time frame:: Week 4
Reported as:: Least squares mean · Unit on a scale

Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4
Unit on a scale	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
High versus low	1.55 ± 0.083	—	1.64 ± 0.062
Mid versus low	1.57 ± 0.089	1.44 ± 0.092	—

Statistical analysis

MP Low Dose Group vs MP High Dose Group · ANCOVA · p = = 0.34 · Ls-mean difference: 0.09 · 95% CI -0.1 to 0.28
MP Low Dose Group vs MP Mid Dose Group · ANCOVA · p = = 0.297 · Ls-mean difference: -0.12 · 95% CI -0.36 to 0.11

SecondaryMP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4

The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.

Time frame:: Baseline and Week 4
Reported as:: Least squares mean · Unit on a scale

MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4
Unit on a scale	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
High versus low	-1.03 ± 0.083	—	-1.13 ± 0.061
Mid versus low	-1.08 ± 0.087	-1.22 ± 0.090	—

SecondaryMP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4

Time frame:: Baseline and Week 4
Reported as:: Least squares mean · Unit on a scale

MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4
Unit on a scale	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
High versus low	-0.53 ± 0.212	—	-1.00 ± 0.133
Mid versus low	-0.070 ± 0.202	-1.04 ± 0.176	—

SecondaryMP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4

Time frame:: Baseline up to Week 4
Reported as:: Least squares mean · Unit on a scale

MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Unit on a scale	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
Flexed elbow: High versus Low	-0.99 ± 0.076	—	-1.18 ± 0.056
Flexed elbow: Mid versus Low	-1.01 ± 0.081	-1.17 ± 0.082	—
Flexed wrist: High versus Low	-0.96 ± 0.085	—	-1.08 ± 0.061
Flexed wrist: Mid versus Low	-1.01 ± 0.087	-1.05 ± 0.087	—
Clenched fist: High versus Low	-0.64 ± 0.136	—	-1.09 ± 0.096
Clenched fist: Mid versus Low	-0.58 ± 0.145	-0.87 ± 0.141	—
Thumb in palm: High versus Low	-0.88 ± 0.116	—	-1.11 ± 0.083
Thumb in palm: Mid versus Low	-0.93 ± 0.131	-1.14 ± 0.123	—
Pronated forearm: High versus Low	-0.88 ± 0.080	—	-1.02 ± 0.058
Pronated forearm: Mid versus Low	-0.87 ± 0.086	-0.94 ± 0.088	—

SecondaryMP: 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)'

Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with QPS. The QPS Total Score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS Total Score for the observed pain frequency ranges from 0 (Never) to 4 (Always). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. P/C = Parent/Caregiver.

Time frame:: Baseline, Weeks 4, 8, and 14
Reported as:: Least squares mean · Unit on a scale

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)'
Unit on a scale	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
UL, Participant, Week 4 High versus low	-0.42 ± 0.217	—	-0.75 ± 0.199
UL, Participant, Week 4 Mid versus low	-0.39 ± 0.256	-0.67 ± 0.289	—
UL, Participant, Week 8 High versus low	-0.52 ± 0.206	—	-0.64 ± 0.188
UL, Participant, Week 8 Mid versus low	-0.63 ± 0.259	-0.55 ± 0.290	—
UL, Participant, Week 14 High versus low	-0.56 ± 0.217	—	-0.59 ± 0.202
UL, Participant, Week 14 Mid versus low	-0.66 ± 0.327	-0.59 ± 0.361	—
UL, P/C, Week 4 High versus low	-0.46 ± 0.102	—	-0.44 ± 0.076
UL, P/C, Week 4 Mid versus low	-0.43 ± 0.106	-0.28 ± 0.115	—
UL, P/C, Week 8 High versus low	-0.40 ± 0.095	—	-0.44 ± 0.070
UL, P/C, Week 8 Mid versus low	-0.43 ± 0.100	-0.34 ± 0.109	—
UL, P/C, Week 14 High versus Low	-0.23 ± 0.105	—	-0.24 ± 0.071
UL, P/C, Week 14 Mid versus Low	-0.31 ± 0.100	-0.25 ± 0.107	—
LL, Participant, Week 4 High versus Low	-0.74 ± 0.282	—	-0.62 ± 0.250
LL, Participant, Week 4 Mid versus Low	-0.46 ± 0.305	-0.55 ± 0.321	—
LL, Participant, Week 8 High versus Low	-1.04 ± 0.241	—	-0.69 ± 0.218
LL, Participant, Week 8 Mid versus Low	-0.90 ± 0.261	-0.81 ± 0.284	—
LL, Participant, Week 14 High versus Low	-0.71 ± 0.275	—	-0.57 ± 0.245
LL, Participant, Week 14 Mid versus Low	-0.67 ± 0.315	-0.63 ± 0.335	—
LL, P/C, Week 4 High versus Low	-0.50 ± 0.105	—	-0.52 ± 0.077
LL, P/C, Week 4 Mid versus Low	-0.46 ± 0.103	-0.42 ± 0.111	—
LL, P/C, Week 8 High versus Low	-0.56 ± 0.098	—	-0.51 ± 0.074
LL, P/C, Week 8 Mid versus Low	-0.52 ± 0.102	-0.36 ± 0.111	—
LL, P/C, Week 14 High versus Low	-0.33 ± 0.108	—	-0.32 ± 0.078
LL, P/C, Week 14 Mid versus Low	-0.37 ± 0.086	-0.31 ± 0.090	—

SecondaryMP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4

The GICS was used to measure independently the child's/adolescent's, and parent's or caregiver's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from: +3(very much improved); +2(much improved); +1(minimally improved); 0(no change); -1(minimally worse); -2(much worse); -3(very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.

Time frame:: Week 4
Reported as:: Least squares mean · Unit on a scale

MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
Unit on a scale	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group
Participant: High versus Low	1.51 ± 0.153	—	1.63 ± 0.139
Participant: Mid versus Low	1.53 ± 0.180	1.48 ± 0.190	—
Parent/Caregiver: High versus Low	1.41 ± 0.087	—	1.60 ± 0.065
Parent/Caregiver: Mid versus Low	1.36 ± 0.094	1.29 ± 0.097	—

SecondaryNumber of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall	21	13	42	114
First injection cycle (MP)	21	13	42	—
Second injection cycle (OLEX)	—	—	—	64
Third injection cycle (OLEX)	—	—	—	42
Fourth injection cycle (OLEX)	—	—	—	48

SecondaryNumber of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall	1	1	1	5
First injection cycle (MP)	1	1	1	—
Second injection cycle (OLEX)	—	—	—	2
Third injection cycle (OLEX)	—	—	—	3
Fourth injection cycle (OLEX)	—	—	—	1

SecondaryNumber of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall	2	1	2	16
First injection cycle (MP)	2	1	2	—
Second injection cycle (OLEX)	—	—	—	7
Third injection cycle (OLEX)	—	—	—	9
Fourth injection cycle (OLEX)	—	—	—	3

SecondaryNumber of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall	0	0	3	5
First injection cycle (MP)	0	0	3	—
Second injection cycle (OLEX)	—	—	—	2
Third injection cycle (OLEX)	—	—	—	2
Fourth injection cycle (OLEX)	—	—	—	1

SecondaryNumber of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall: Mild	15	10	33	62
Overall: Moderate	6	2	7	44
Overall: Severe	0	1	2	8
First injection cycle (MP): Mild	15	10	33	—
First injection cycle (MP): Moderate	6	2	7	—
First injection cycle (MP): Severe	0	1	2	—
Second injection cycle (OLEX): Mild	—	—	—	43
Second injection cycle (OLEX): Moderate	—	—	—	18
Second injection cycle (OLEX): Severe	—	—	—	3
Third injection cycle (OLEX): Mild	—	—	—	23
Third injection cycle (OLEX): Moderate	—	—	—	15
Third injection cycle (OLEX): Severe	—	—	—	4
Fourth injection cycle (OLEX): Mild	—	—	—	28
Fourth injection cycle (OLEX): Moderate	—	—	—	19
Fourth injection cycle (OLEX): Severe	—	—	—	1

SecondaryNumber of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall: Related	0	0	3	5
Overall: Not related	21	13	39	109
First injection cycle (MP): Related	0	0	3	—
First injection cycle (MP): Not related	21	13	39	—
Second injection cycle (OLEX): Related	—	—	—	2
Second injection cycle (OLEX): Not related	—	—	—	62
Third injection cycle (OLEX): Related	—	—	—	2
Third injection cycle (OLEX): Not related	—	—	—	40
Fourth injection cycle (OLEX): Related	—	—	—	1
Fourth injection cycle (OLEX): Not related	—	—	—	47

SecondaryNumber of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall: Resolved	18	10	39	96
Overall: Resolved with sequelae	1	0	0	1
Overall: Resolving	0	2	1	7
Overall: Not resolved	2	1	1	8
Overall: Unknown	0	0	1	2
Overall: Fatal	0	0	0	0
First injection cycle (MP): Resolved	18	10	39	—
First injection cycle (MP): Resolved with sequelae	1	0	0	—
First injection cycle (MP): Resolving	0	2	1	—
First injection cycle (MP): Not resolved	2	1	1	—
First injection cycle (MP): Unknown	0	0	1	—
First injection cycle (MP): Fatal	0	0	0	—
Second injection cycle (OLEX): Resolved	—	—	—	57
Secondinjection cycle(OLEX):Resolved with sequelae	—	—	—	0
Second injection cycle (OLEX): Resolving	—	—	—	3
Second injection cycle (OLEX): Not resolved	—	—	—	4
Second injection cycle (OLEX): Unknown	—	—	—	0
Second injection cycle (OLEX): Fatal	—	—	—	0
Third injection cycle (OLEX): Resolved	—	—	—	37
Third injection cycle(OLEX):Resolved with sequelae	—	—	—	0
Third injection cycle (OLEX): Resolving	—	—	—	0
Third injection cycle (OLEX): Not resolved	—	—	—	4
Third injection cycle (OLEX): Unknown	—	—	—	1
Third injection cycle (OLEX): Fatal	—	—	—	0
Fourth injection cycle (OLEX): Resolved	—	—	—	39
Fourthinjection cycle(OLEX):Resolved with sequelae	—	—	—	1
Fourth injection cycle (OLEX): Resolving	—	—	—	4
Fourth injection cycle (OLEX): Not resolved	—	—	—	2
Fourth injection cycle (OLEX): Unknown	—	—	—	2
Fourth injection cycle (OLEX): Fatal	—	—	—	0

SecondaryNumber of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle

Time frame:: Baseline up to Week 66
Reported as:: Count of participants · Participants

Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Participants	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
Overall	0	1	1	5
First injection cycle (MP)	0	1	1	—
Second injection cycle (OLEX)	—	—	—	3
Third injection cycle (OLEX)	—	—	—	2
Fourth injection cycle (OLEX)	—	—	—	0

Adverse events

Collected over Baseline up to Week 66. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
MP Low Dose Group	0/87 (0%)	2/87 (2.3%)	5/87 (5.7%)
MP Mid Dose Group	0/87 (0%)	1/87 (1.1%)	3/87 (3.4%)
MP High Dose Group	0/176 (0%)	2/176 (1.1%)	6/176 (3.4%)
OLEX (3 Injections)	0/331 (0%)	16/331 (4.8%)	18/331 (5.4%)

Most frequent serious events

Showing 10 of 30

Most frequent serious events
Event	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
BronchitisInfections and infestations	2/87	0/87	1/176	0/331
AspirationRespiratory, thoracic and mediastinal disorders	0/87	1/87	0/176	0/331
Respiratory arrestRespiratory, thoracic and mediastinal disorders	0/87	1/87	0/176	0/331
Brain oedemaNervous system disorders	0/87	1/87	0/176	0/331
EpilepsyNervous system disorders	1/87	0/87	0/176	1/331
PneumoniaInfections and infestations	0/87	0/87	2/176	0/331
SeizureNervous system disorders	0/87	0/87	0/176	2/331
Hiatus herniaGastrointestinal disorders	0/87	0/87	0/176	2/331
Shunt malfunctionInjury, poisoning and procedural complications	0/87	0/87	0/176	1/331
Thermal burnInjury, poisoning and procedural complications	0/87	0/87	0/176	1/331

Most frequent other events

Most frequent other events
Event	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	OLEX (3 Injections)
NasopharyngitisInfections and infestations	5/87	3/87	6/176	18/331

Baseline characteristics

The analysis population included all randomized participants.

Age, Continuous
Age, Continuous(Years)	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	Total
Mean	7.2 ± 4.70	7.4 ± 4.13	7.3 ± 4.40	7.3 ± 4.40

Sex: Female, Male
Sex: Female, Male(Participants)	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	Total
Female	38	31	62	131
Male	49	57	114	220

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	Total
Hispanic or Latino	16	26	45	87
Not Hispanic or Latino	71	62	131	264

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	MP Low Dose Group	MP Mid Dose Group	MP High Dose Group	Total
Black or African American	3	2	2	7
White	81	75	160	316
Other	3	11	14	28

Study locations

32 sites

Merz Investigational Site #001286
Gulf Breeze, Florida 32561, United States
Merz Investigational Site #001284
Loxahatchee Groves, Florida 33470, United States
Merz Investigational Site #001285
Savannah, Georgia 31405, United States
Merz Investigational Site #001186
Chicago, Illinois 60611, United States
Merz Investigational Site No. #001302
Royal Oak, Michigan 48073, United States
Merz Investigational Site #001283
Columbia, Missouri 65212, United States
Merz Investigational Site #054010
Godoy Cruz, Provincia De Mendoza M5501, Argentina
Merz Investigational Site #054005
Caba, CP 1428, Argentina
Merz Investigational Site #052023
Aguascalientes, 20127, Mexico
Merz Investigational Site #052003
Guadalajara, 44280, Mexico
Merz Investigational Site #052024
Mexico City, 04530, Mexico
Merz Investigational Site #052022
Mexico City, 06700, Mexico
Merz Investigational Site #052027
Monterrey, 64060, Mexico
Merz Investigational Site #052028
Monterrey, 64710, Mexico
Merz Investigational Site #052026
Zapopan, 45030, Mexico
Merz Investigational Site #048089
Bialystok, 15-274, Poland
Merz Investigational Site #048063
Gdansk, 80-389, Poland
Merz Investigational Site #048059
Krakow, 30-539, Poland
Merz Investigational Site #048084
Lublin, 20-828, Poland
Merz Investigational Site #048094
Poznan, 60-480, Poland
Merz Investigational Site #048075
Sandomierz, 27-600, Poland
Merz Investigational Site #048060
Wiazowna, 05-462, Poland
Merz Investigational Site #007014
Kazan, 420097, Russian Federation
Merz Investigational Site #007015
Khabarovsk, 680038, Russian Federation
Merz Investigational Site #007018
Novosibirsk, 630091, Russian Federation
Merz Investigational Site #007298
Saint Petersburg, 192148, Russian Federation
Merz Investigational Site #007013
Smolensk, 214019, Russian Federation
Merz Investigational Site #007019
Stavropol, 355029, Russian Federation
Merz Investigational Site #380001
Dnipropetrovsk, 49000, Ukraine
Merz Investigational Site #380005
Kharkiv, 61068, Ukraine
Merz Investigational Site #380002
Kyiv, 04209, Ukraine
Merz Investigational Site #380003
Odessa, 65012, Ukraine

References and documents

Publications

Dabrowski E, Chambers HG, Gaebler-Spira D, Banach M, Kanovsky P, Dersch H, Althaus M, Geister TL, Heinen F. IncobotulinumtoxinA Efficacy/Safety in Upper-Limb Spasticity in Pediatric Cerebral Palsy: Randomized Controlled Trial. Pediatr Neurol. 2021 Oct;123:10-20. doi: 10.1016/j.pediatrneurol.2021.05.014. Epub 2021 May 21. PubMed 34339951 ↗
Berweck S, Banach M, Gaebler-Spira D, Chambers HG, Schroeder AS, Geister TL, Althaus M, Hanschmann A, Vacchelli M, Bonfert MV, Heinen F, Dabrowski E. Safety Profile and Lack of Immunogenicity of IncobotulinumtoxinA in Pediatric Spasticity and Sialorrhea: A Pooled Analysis. Toxins (Basel). 2022 Aug 25;14(9):585. doi: 10.3390/toxins14090585. PubMed 36136523 ↗

Study documents

Study protocol · Apr 7, 2016
Statistical analysis plan · Oct 18, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 5, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02002884
Lead sponsor: Merz Pharmaceuticals GmbH
Responsible party: Sponsor
First posted: Dec 6, 2013
Start date: Mar 28, 2014
Primary completion: Jul 4, 2017
Completion: Aug 28, 2018
Results posted: Aug 3, 2020
Last update: Aug 5, 2021

Study contacts

Merz Medical Expert

study director · Merz Pharmaceuticals GmbH

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2020. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Muscle Spasticity→

Other studies from this sponsor

Merz Pharmaceuticals GmbH

Start the discussion

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

Study summary

Conditions studied

Browse trials for

Keywords

In context

Muscle Spasticity

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

References and documents

Publications

Study documents

Individual participant data

Updates

Registry details

Key details

Study contacts

Oversight

Not currently enrolling

Follow this study

Discussion

Other studies in this condition

Other studies from this sponsor

Inclusion criteria

Exclusion criteria