Ipsen today announced that the scientific journal Pediatrics published1 the detailed results of the phase III randomized study (NCT01249417) showing both the efficacy and the safety of Dysport® in the treatment of dynamic equinus foot deformity (also known as pediatric lower limb spasticity), a condition associated with cerebral palsy in children.
The study met the primary endpoint (Modified Ashworth Scale, MAS) and the first secondary endpoint (Physician Global Assessment, PGA) in children with dynamic equinus foot deformity who received injections of Dysport® in the gastrocnemius and soleus calf muscles. Dysport® showed statistically significant improvement in muscle tone, resulting in an improved overall clinical benefit at week 4 at the two dose levels tested (10 and 15U/kg for unilateral injection or 20 and 30U/kg for bilateral injections). In addition, improvement of spasticity and attainment of overall treatment goals were demonstrated in a statistically and clinically significant manner as compared to placebo at week 4 after injection. Both doses of Dysport® were well tolerated and there was no evidence of a dose relationship for adverse events. The most frequent treatment emergent adverse events were common childhood infections (upper respiratory tract infections).
Claude Bertrand, Executive Vice President R&D and Chief Scientific Officer, Ipsen stated: “The peer-reviewed publication of these Phase 3 results in the journal Pediatrics confirms the favorable efficacy and safety profile of Dysport® in the treatment of lower limb spasticity in children with cerebral palsy and demonstrates improvement in functional benefit after a single injection of Dysport®. The study results confirm the therapeutic value of Dysport® in this debilitating condition, the most common cause of chronic motor disability in childhood2;3;4. ”
Professor Mauricio Delgado, Director of the Pediatric Neurology Department at Texas Scottish Rite Hospital for Children and Professor of Neurology and Neurotherapeutics at the University of Texas Southwestern Medical Center) and Principal Investigator of the study stated: “The publication of this study in Pediatrics is important news for the field of pediatric neurorehabilitation and for the treatment of children with equinus foot deformity due to cerebral palsy. This is the first international study that demonstrates substantial improvements in muscle tone and spasticity translating into clinical and functional benefits after a single injection in this patient population. This study both highlights the potential therapeutic value of Dysport® (abobotulinum toxin) in children with cerebral palsy and shows the potential value of new assessment methods that could have practical clinical application.”
About the Double Blind Phase 3 Study in cerebral palsy (hemiplegic and diplegic) children with lower limb spasticity
The Phase III study (NCT01249417) was multi-center, prospective, double blind, randomized, and placebo-controlled. It was conducted in the U.S., Mexico, Chile, Turkey, France and Poland.
A total of 241 patients from 27 centers were randomized to treatment with Dysport® 10U/kg/leg (n=80), Dysport® 15U/kg/leg (n=80) or placebo (n=81). The purpose of this study was to assess the efficacy of Dysport® compared to placebo in the treatment of Lower Limb Spasticity in children with cerebral palsy. Muscle tone and spasticity were assessed using the MAS and the Tardieu Scale; patient functionality was assessed using the Physician’s Global Assessment (PGA) and goal attainment scaling (GAS).
Study results showed a significant improvement versus placebo on muscle tone at both doses at week 4 post-injection (Primary endpoint – Assessment scale: Modified Ashworth Scale) with abobotulinumtoxinA; mean [95%CI] treatment differences vs. placebo were: -0.49 [-0.75, -0.23] (p=0.0002) for 15U/kg/leg and – 0.38 [-0.64, -0.13] (p=0.003) for 10U/kg/leg.
A significant improvement was also observed on the overall clinical improvement (first secondary endpoint – Physician Global Assessment) with mean treatment differences vs. placebo of 0.77 [ 0.45, 1.10 ] for 15U/kg/leg and 0.82 [ 0.50, 1.14 ] for 10U/kg/leg (both p<0.0001).
In addition, significant improvement in spasticity (tertiary endpoint – using the Tardieu scale) was observed at Week 4. Both doses improved the Tardieu scale spasticity grade Y at 4 Weeks (p<0.001). For the 15U/kg/leg dose, Week 4 improvements were also accompanied by significant improvements in the angle of catch XV3 (p=0.0003) and angle of arrest XV1 (p=0.01).
The use of Goal Attainment Scale clearly demonstrates that improvements in tone and spasticity allow the patients to achieve their overall functional goals, namely those related to walking and gait patternat both doses tested at Week 4.
Both doses of Dysport® were well tolerated and there was no evidence of a dose relationship for adverse events (AEs). The most frequent TEAEs (treatment emergent adverse events) were common childhood infections (upper respiratory tract infections). Five patients in the abobotulinumtoxinA groups had an AE of epilepsy recorded versus none in the placebo group, however none was considered related to study treatment and there was an over-representation of epilepsy in the treatment groups.
After the completion of this double blind study, patients were offered the option to continue in an open label long-term study where they would receive additional treatment with Dysport®.
Dysport® is an injectable form of botulinum toxin type A (BTX-A), which is isolated and purified from Clostridium BTX-A bacteria. It is supplied as a lyophilized powder.
Dysport® was first registered for the treatment of blepharospasm and hemifacial spasm in the United Kingdom in 1990. It is licensed in 82 countries for various indications including blepharospasm, upper and lower limb spasticity in adults, hemifacial spasm, spasmodic torticollis (also referred to as cervical dystonia), lower limb spasticity due to cerebral palsy in children, axillary hyperhidrosis and glabellar lines.
Dysport® is approved for the treatment of lower limb spasticity in children in many European and international markets, but not in the United States (USA). As such, data from studies of Dysport® in children with lower limb spasticity are investigational in the USA.
1 online at http://pediatrics.aappublications.org/content/early/2016/01/24/peds.2015-2830
2 Delgado MR, Albright AL. Movement disorders in children: definitions, classifications, and grading systems. J Child Neurol. 2003;18 Suppl 1:S1-8.
3 Aisen ML, Kerkovich D, Mast J, et al. Cerebral palsy: clinical care and neurological rehabilitation. Lancet Neurol. 2011;10(9):844-852.
4 Yeargin-Allsopp M, Van Naarden Braun K, Doernberg NS, Benedict RE, Kirby RS, Durkin MS. Prevalence of cerebral palsy in 8-year-old children in three areas of the United States in 2002: a multisite collaboration. Pediatrics. 2008;121(3):547-554.