Cerebral PalsyPhase 3XARANCT02002884
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 study testing IncobotulinumtoxinA (8 Units per kg body weight), IncobotulinumtoxinA (6 Units per kg body weight) and IncobotulinumtoxinA (2 Units per kg body weight) in people with Cerebral Palsy and Spasticity, run by Merz Pharmaceuticals GmbH at 32 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Cerebral Palsy, Spasticity
- What is being tested?
- IncobotulinumtoxinA (8 Units per kg body weight), IncobotulinumtoxinA (6 Units per kg body weight) and IncobotulinumtoxinA (2 Units per kg body weight)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 351 participants
- Where
- 32 sitesin 6 countries
- Study dates
- 28 Mar 2014to 28 Aug 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Show all 43Show fewer
- 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.
- 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.
- 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.
- 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.
- 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.
Who cannot join
- Pre-treated (non-naïve) subjects must not have received BoNT treatment within the last 14 weeks prior to Screening Visit (V1) in any indication.
Trial locations and contacts
32 sites in 6 countries.
32 sites in 6 countries
Mexico7 sites
Merz Investigational Site #052023
Aguascalientes, 20127
Merz Investigational Site #052003
Guadalajara, 44280
Merz Investigational Site #052024
Mexico City, 04530
Merz Investigational Site #052022
Mexico City, 06700
Merz Investigational Site #052027
Monterrey, 64060
Merz Investigational Site #052028
Monterrey, 64710
Merz Investigational Site #052026
Zapopan, 45030
Poland7 sites
Merz Investigational Site #048089
Bialystok, 15-274
Merz Investigational Site #048063
Gdansk, 80-389
Merz Investigational Site #048059
Krakow, 30-539
Merz Investigational Site #048084
Lublin, 20-828
Merz Investigational Site #048094
Poznan, 60-480
Merz Investigational Site #048075
Sandomierz, 27-600
Merz Investigational Site #048060
Wiązowna, 05-462
United States6 sites
Merz Investigational Site #001186
Chicago, Illinois, 60611
Merz Investigational Site #001283
Columbia, Missouri, 65212
Merz Investigational Site #001286
Gulf Breeze, Florida, 32561
Merz Investigational Site #001284
Loxahatchee Groves, Florida, 33470
Merz Investigational Site No. #001302
Royal Oak, Michigan, 48073
Merz Investigational Site #001285
Savannah, Georgia, 31405
Russia6 sites
Merz Investigational Site #007014
Kazan', 420097
Merz Investigational Site #007015
Khabarovsk, 680038
Merz Investigational Site #007018
Novosibirsk, 630091
Merz Investigational Site #007298
Saint Petersburg, 192148
Merz Investigational Site #007013
Smolensk, 214019
Merz Investigational Site #007019
Stavropol, 355029
Ukraine4 sites
Merz Investigational Site #380001
Dnipropetrovsk, 49000
Merz Investigational Site #380005
Kharkiv, 61068
Merz Investigational Site #380002
Kyiv, 04209
Merz Investigational Site #380003
Odesa, 65012
Argentina2 sites
Merz Investigational Site #054005
Caba, CP 1428
Merz Investigational Site #054010
Godoy Cruz, Mendoza Province, M5501
About this study
Official title: Prospective, Multicenter, Randomized, Double-blind, Parallel-group, Dose-response Study of Three Doses Xeomin® (incobotulinumtoxinA, NT 201) for the Treatment of Upper Limb Spasticity Alone or Combined Upper and Lower Limb Spasticity in Children and Adolescents (Age 2 - 17 Years) With Cerebral Palsy
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
- Cerebral Palsy, Spasticity
- Being tested
- IncobotulinumtoxinA (8 Units per kg body weight), IncobotulinumtoxinA (6 Units per kg body weight), IncobotulinumtoxinA (2 Units per kg body weight)
- Keywords
- Upper limb spasticity, lower limb spasticity, combined upper and lower limb spasticity
- Medical subject headings
- Cerebral Palsy, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IncobotulinumtoxinA (8 Units per kg body weight)Drug
Also called Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
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.
IncobotulinumtoxinA (6 Units per kg body weight)Drug
Also called Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
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.
IncobotulinumtoxinA (2 Units per kg body weight)Drug
Also called Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
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.
| Study group | Role | What they receive |
|---|---|---|
| 8 Units per kg body weight incobotulinumtoxinA (Xeomin) | Experimental | 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. Receives: Drug: IncobotulinumtoxinA (8 Units per kg body weight) |
| 6 Units per kg body weight incobotulinumtoxinA (Xeomin) | Experimental | 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. Receives: Drug: IncobotulinumtoxinA (6 Units per kg body weight) |
| 2 Units per kg body weight incobotulinumtoxinA (Xeomin) | Experimental | 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. Receives: Drug: IncobotulinumtoxinA (2 Units per kg body weight) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Week 4
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 4
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Measured: Baseline up to Week 66
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2013 (estimated)
- Study start28 Mar 2014
- Primary completion4 Jul 2017
- Study completion28 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cerebral PalsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 351 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merz Pharmaceuticals GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Merz Medical Expert, Study director, Merz Pharmaceuticals GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02002884
- Sponsor's protocol ID
- MRZ60201_3072_1
- Other IDs
- 2012-005496-14
- Acronym
- XARA
- Status last verified
- Jul 2020
- First submitted
- 2 Dec 2013
- Last updated
- 5 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 34339951Berweck 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 at a glance
From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Multicenter, Randomized, Double-blind, Parallel-group, Dose-response Study of Three Doses Xeomin® (incobotulinumtoxinA, NT 201) for the Treatment of Upper Limb Spasticity Alone or Combined Upper and Lower Limb Spasticity in Children and Adolescents (Age 2 - 17 Years) With Cerebral Palsy
- ClinicalTrials.gov ID
- NCT02002884
- Acronym / sponsor ID
- XARA / MRZ60201_3072_1
- Conditions
- Cerebral Palsy, Spasticity
- Keywords
- Upper limb spasticity, lower limb spasticity, combined upper and lower limb spasticity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 351 participants (actual)
- Lead sponsor
- Merz Pharmaceuticals GmbHIndustry (pharma, biotech, devices)
- Study start
- 28 Mar 2014 (actual)
- Primary completion
- 4 Jul 2017 (actual)
- Study completion
- 28 Aug 2018 (actual)
- First posted
- 6 Dec 2013 (estimated)
- Results
- Posted 3 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 8 Units per kg body weight incobotulinumtoxinA (Xeomin) | Experimental | Drug: IncobotulinumtoxinA (8 Units per kg body weight)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. |
| 6 Units per kg body weight incobotulinumtoxinA (Xeomin) | Experimental | Drug: IncobotulinumtoxinA (6 Units per kg body weight)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. |
| 2 Units per kg body weight incobotulinumtoxinA (Xeomin) | Experimental | Drug: IncobotulinumtoxinA (2 Units per kg body weight)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. |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (43 listed)
- 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:
- 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.
- UL(s) treatment only (GMFCS I-V):
Key exclusion criteria (1 listed)
- Pre-treated (non-naïve) subjects must not have received BoNT treatment within the last 14 weeks prior to Screening Visit (V1) in any indication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IncobotulinumtoxinA (8 Units per kg body weight)Also: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteinsActive 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. | Drug | 8 Units per kg body weight incobotulinumtoxinA (Xeomin) |
| IncobotulinumtoxinA (6 Units per kg body weight)Also: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteinsActive 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. | Drug | 6 Units per kg body weight incobotulinumtoxinA (Xeomin) |
| IncobotulinumtoxinA (2 Units per kg body weight)Also: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteinsActive 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. | Drug | 2 Units per kg body weight incobotulinumtoxinA (Xeomin) |
Primary outcome
MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4
Time frame: Baseline and 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.
Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4
Time frame: 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.
13 secondary outcomes
MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4
Time frame: Baseline and Week 4
MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4
Time frame: Baseline and Week 4
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
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)'
Time frame: Baseline, Weeks 4, 8, and 14
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34339951Dabrowski 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.
- Derived from this study: PubMed 36136523Berweck 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Merz Medical Expert study director
Merz Pharmaceuticals GmbH
32 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IncobotulinumtoxinA (8 Units per kg body weight), IncobotulinumtoxinA (6 Units per kg body weight) and IncobotulinumtoxinA (2 Units per kg body weight) in people with Cerebral Palsy and Spasticity, run by Merz Pharmaceuticals GmbH at 32 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 43 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Mexico, Poland, United States, Russia, Ukraine and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4 (time frame: Baseline and Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02002884, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2021.