Treatment of Spasticity in the lower limb in childre

Phase 1

• Conditions: ower Limb Spasticity; MedDRA version: 19.0Level: PTClassification code 10028335Term: Muscle spasticitySystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 19.0Level: LLTClassification code 10024132Term: Leg spasticitySystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2012-000084-24-PL
• Lead Sponsor: Allergan Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-11-02
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

Rollover patients:
• Eligible patients who successfully completed Allergan Study 191622-111 without major protocol deviations (eg, noncompliance to protocol-required procedures) and who, in the investigator’s clinical judgment, did not experience an adverse event that may indicate an unacceptable safety risk for additional BOTOX treatments
• Stable medical condition in the investigator’s opinion
• 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 day 1 visit (for females of childbearing potential, defined as females post menarche)

De novo patients:
• Male or female, 2 to 16 years and 11 months of age (prior to 17th birthday) at day 1 visit
• Minimum weight of 10 kg at the screening and day 1 visits
• Monoplegic, hemiplegic, or diplegic patients with cerebral palsy with dynamic muscle contracture (spasticity confirmed by Hypertonia Assessment Tool [HAT]) of the ankle plantar flexors. Equinovarus and 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 the screening and day 1 visits
• 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 IRB/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 US sites and written Data Protection consent for 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: 350
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

Exclusion Criteria

Key Exclusion Criteria (all patients except where noted otherwise):
- Any uncontrolled clinically significant medical condition other than the condition 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
- Monoplegic or hemiplegic patients with the following gait patterns in the study lower limb:
Type 1: drop foot or Type IV: equinus with jump knee, or pelvic rotation, hip flexed, adducted, or internal rotation (see Figure 3) (de novo patients only)
- Diplegic patients with the following gait patterns in the lower limbs: apparent equinus or crouch gait (see Figure 4) (de novo patients only)
- Fixed contracture of the ankle for the study limb
- Uncontrolled epilepsy defined as more than 1 generalized seizure in any month within the 3 months prior to the day 1 visit or history of any of the following within 9 months prior to the day 1 visit: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.
- Patients with presence or history of any of the following within 12 months prior to the day 1 visit that may indicate a vulnerable respiratory state per the investigator’s clinical judgment:aspiration pneumonia, recurrent lower respiratory tract infections, uncontrolled asthma, or compromised respiratory function.
- 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 3 months prior to the day 1 visit (de novo patients only)
- History of treatment with phenol or alcohol block in the study lower limb(s) within 6 months prior to the day 1 visit (de novo patients only) or planned treatment with phenol or alcohol block in the study lower 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[s]) within 12 months prior to the day 1 visit (de novo patients only) or planned surgical intervention of any limb(s) during the study
- Females who are pregnant, nursing, or planning a pregnancy during the study
- Females of childbearing potential (defined as females post menarche) not using reliable means of contraception (see Section 4.5.1.1 for acceptable contraceptive methods)
- Patients with a significant risk of suicide within the 12 months prior to screening, or since screening at the day 1 visit (de novo

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 long-term safety of repeated doses of BOTOX for the treatment of pediatric lower limb spasticity;Secondary Objective: None;Primary end point(s): No primary efficacy variable is identified.;Timepoint(s) of evaluation of this end point: Not applicable

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Grade change from baseline in MAS-B ankle at each follow-up visit<br>• CGI by Physician at each follow-up visit<br>• The difference between slow (R2) and fast (R1) motion in degree (R2 - R1) and the individual R2 and R1 on the MTS of the ankle of the study lower limb, and changes from baseline<br>• Edinburgh Visual Gait score (patients with GMFCS-E&R level I to III; at selected sites)<br>• Faces Pain Scale-Revised (for patients who are 4 years and older at day 1 and reported pain [score > 0] at the day 1 visit);Timepoint(s) of evaluation of this end point: Evaluations at every visit.