Treatment of Spasticity in the lower limb in childre
- Conditions
- ower Limb SpasticityMedDRA version: 14.1Level: LLTClassification code 10024132Term: Leg spasticitySystem Organ Class: 10029205 - Nervous system disordersMedDRA version: 14.1Level: PTClassification code 10028335Term: Muscle spasticitySystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2012-000042-35-DE
- Lead Sponsor
- Allergan Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 412
• Male or female, 2 to 16 years and 11 months of age (prior to 17th birthday) at the day 1 visit
• Minimum weight of 10 kg at the screening and day 1 visits
• Monoplegic or hemiplegic patients with cerebral palsy who have dynamic muscle contracture (spasticity confirmed by Hypertonia Assessment Tool [HAT]) of the ankle plantar flexors associated with true equinus foot deformity as described by Rodda and Graham (2001; see Figure 1 in exclusion criteria). Equinovarus or equinovalgus deformities are acceptable.
• MAS-B score = 2 for the ankle plantar flexors and minimum range of dorsiflexion of 0 degrees of the ankle with knee fully extended in the study limb at screening and day 1 visits
• Patients for whom study treatment in the 3 ankle plantar flexors (namely gastrocnemius, soleus, and tibialis posterior) of the study leg is appropriate
• Gross Motor Function Classification System – Expanded and Revised (GMFCS-E&R) level I to IV at the screening visit
• Patients who are on anti-spastic medications or muscle relaxants (eg, oral baclofen, tizanidine, dantrolene, scopolamine [oral or patch], vigabatrin, or benzodiazepine therapy) must be on a stable dose and regimen for at least 30 days prior to the day 1 visit
• Patients who are on anti-epileptic medications must be on a stable dose and regimen for at least 30 days prior to the day 1 visit
• Written informed consent has been obtained from parent/legally authorized representative
• Written minor assent has been obtained in accordance with local laws and institutional review board (IRB)/independent ethics committee (IEC) requirements
• Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information for United States [US] sites and written Data Protection consent for European Union [EU] sites)
• Negative urine pregnancy test at the screening and day 1 visits (for females of childbearing potential, defined as females post menarche)
Are the trial subjects under 18? yes
Number of subjects for this age range: 412
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
• Any uncontrolled clinically significant medical condition other than the one under study
• Any medical condition that may put the patient at increased risk with exposure to Botulinum Toxin Type A Purified Neurotoxin Complex, including diagnosed muscular dystrophy (eg, Duchenne’s muscular dystrophy), myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, mitochondrial disease, or any other significant disease that might interfere with neuromuscular function
• Fixed contracture of the ankle for the study limb
• Patients with clinically significant spasticity of the knee flexors in the study limb (defined as either MAS-B knee score higher than MAS-B ankle score [with knee extended] or MAS-B knee score > 2 at the screening or day 1 visit) and require BOTOX injection to the knee flexors during the study
• Patients with the following gait patterns in the study limb: Type 1 drop foot” or Type IV equinus with jump knee, or pelvic rotation, hip flexed, adducted, or internal rotation” (see Figure 1)
• Uncontrolled epilepsy defined as more than 1 generalized seizure per month within 3 months prior to the day 1 visit or history of prolonged seizures or repetitive seizure activity requiring administration of a rescue benzodiazepine (oral, rectal, etc) more than once a month, seizures lasting more than
10 minutes, status epilepticus, or epilepsy with autonomic involvement within 9 months prior to the day 1 visit
• Patients with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, uncontrolled asthma, or compromised respiratory function within 12 months prior to the day 1 visit that may indicate a vulnerable respiratory state per the investigator’s clinical judgment
• Patients with presence or history (within 12 months prior to the day 1 visit) of aspiration or a condition(s) that, in the investigator’s opinion, may put the patient at an increased risk for aspiration (eg, significant drooling, chronic dysphagia [difficulty swallowing] requiring changes in diet, or clinically significant gastroesophageal reflux disease)
• Patients previously exposed to botulinum toxin therapy of any serotype who have a history of allergy or sensitivity to the toxin or its components or other significant adverse experiences that, in the investigator’s opinion, may put the patient at an unacceptable risk
• Botulinum toxin therapy of any serotype for any condition within 6 months prior to the day 1 visit
• Patients who are on an active intrathecal baclofen pump therapy within 7 days prior to the day 1 visit or plan to receive such therapy during the study
• History of treatment with phenol or alcohol block in the study limb within 12 months prior to the day 1 visit or planned treatment with phenol or alcohol block in any limb(s) during the study
• History of or planned treatment during the study with selective dorsal rhizotomy or deep brain stimulation
• History of surgical intervention of the lower leg (the knee and below of the study limb; except for tendon lengthening more than 12 months prior to the day 1 visit) or planned surgical intervention of any limb(s) during the study
• Previous casting within 6 months prior to the day 1 visit or splinting with a dynamic splint (eg, Dynasplint® or UltraFlex) within 3 months prior to the day 1 visit for spasticity of the study limb or the affected upper limb, or planned casting or splinting with a dynamic splint (eg, Dynasplint or UltraFlex)
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Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and efficacy of a single treatment of 2 doses (4 U/kg and 8 U/kg) of BOTOX with standardized PT in pediatric patients with lower limb spasticity.;Secondary Objective: None;Primary end point(s): The primary efficacy endpoints will be the average grade change from baseline to weeks 4 and 6 in MAS-B and the average CGI by Physician score at weeks 4 and 6.;Timepoint(s) of evaluation of this end point: Baseline, week 4 and week 6.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Functional goals, active and passive, using GAS by Physician will be evaluated separately relative to baseline at weeks 8 and 12. <br><br>Secondary efficacy variables of the Modified Tardieu Scale (MTS) include the difference between slow (R2) and fast (R1) range of motion (R2 - R1) as well as respective change from baseline on the MTS for the ankle plantar flexors at weeks 2, 4, 6, 8, and 12.<br><br>Additionally changes from baseline for each R1 and R2 at each assessment point will be evaluated.;Timepoint(s) of evaluation of this end point: Baseline, weeks 2, 4, 6, 8, 12.