| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Lower limb spasticity in children with dynamic equinus foot deformity due to cerebral palsy. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10024132 | | E.1.2 | Term | Leg spasticity | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | The primary study objective will be to assess the efficacy of Dysport compared to placebo at Week 4 on the mean change from baseline in ankle joint hypertonicity in children with dynamic equinus foot deformity associated with cerebral palsy (CP). | |
| E.2.2 | Secondary objectives of the trial | The secondary study objectives will include assessments of the efficacy of Dysport compared to placebo on global improvement as measured by the Physician’s Global Assessment (PGA), and on attainment of treatment goals as measured by the Goal
Attainment Scale (GAS). | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Subjects must satisfy all of the following inclusion criteria to be eligible for the
study:
(1) Signed informed consent obtained from the child’s parent(s)/guardian(s) and a signed assent from the child when and where applicable.
(2) Be from 2 to 17 years of age, inclusive.
(3) Have a diagnosis of CP as defined by Rosenbloom.
(4) Be ambulatory with spastic hemiparesis, paraparesis, diparesis or tetraparesis characterised by an equinus foot positioning during the stance phase of the gait.
(5) Have ability to walk (sufficient to complete video 2D motion analysis) with or without walking aids.
(6) Have a MAS score ≥2 at the ankle joint of the (most) affected lower limb
to be injected.
(7) Have a spasticity grade (Y) between 2 and 4, inclusive on the TS assessed at the ankle joint of the most affected limb to be injected with a spasticity angle (X) of 10o or more.
(8) Be classified as GMFCS Level 1 to 3, inclusive.
(9) Botulinum toxin naïve subjects or subjects having received their last BTX treatment of any type more than six months prior to study entry for any condition.
(10) If undergoing pre-study physiotherapy, it must have begun at least one month prior to study start and be continued during the study at the same pre-study frequency and intensity (as well as maintaining the usual level of physical activity until the end of the study) up to at least the Week 12 visit.
(11) Be instructed and willing to use their casting/ orthoses in the same way as before entry into the study until the end of the Week 12 visit. | |
| E.4 | Principal exclusion criteria | Subjects are to be excluded if any of the following applies:
(1) Diagnosed as resistant to BTX treatment of any type.
(2) Evidence of non-ambulatory status.
(3) Fixed myocontracture defined by a passive range of motion (Xv1) of 10°
or less in ankle dorsiflexion.
(4) Subjects likely to be treated with BTX in the upper limbs during the course
of this double blind study.
(5) Severe athetoid or dystonic movements in the targeted lower limb(s).
(6) Significant difference (>2 cm) between the length of legs, defined
clinically and confirmed, as required, by scanogram.
(7) Current need for surgery or previous surgery for spasticity of the lower
limb muscles.
(8) Serial casting in the past 12 weeks.
(9) Previous injection of alcohol and/or phenol into the lower limb(s).
(10) Treatment with any drug that interferes either directly or indirectly with neuromuscular function (e.g. aminoglycoside antibiotics) or neuroblocking agents used during surgery (e.g. curare) within the last 30 days prior to study treatment.
(11) Be pregnant and/or lactating.
(12) Female subjects, not willing to use contraceptive measures throughout the course of the study if post-pubertal and sexually active.
(13) Inability or unwillingness to comply with the protocol.
(14) Subjects with any clinical (or sub-clinical) evidence of marked defective neuromuscular transmission (e.g. Lambert-Eaton syndrome or myasthenia gravis) or persistent clinically significant neuromuscular disorders.
(15) Known sensitivity to BTX or to any of the components in the formulation.
(16) An infection at the injection site(s).
(17) Ongoing treatment with intrathecal baclofen or previous/planned rhizotomy.
(18) Treatment with a new investigational drug within 30 days prior to enrolment into the study or are scheduled to receive such a drug during the study period.
(19) Any medical condition, laboratory or diagnostic procedure finding, which might compromise compliance with the objectives and procedures of this protocol or preclude administration of BTX-A, as judged by the Investigator. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Mean change from baseline to Week 4 in the MAS score at the ankle joint of the (most) affected lower limb. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
