Efficacy and Safety of IncobotulinumtoxinA in Pediatric Upper and Lower Limb Spasticity Due to Cerebral Palsy: A Dose Titration Study

The primary objective of this study is to evaluate the **efficacy** of IncobotulinumtoxinA in treating both BoNT-A naïve and pretreated children with upper and lower limb spasticity due to cerebral palsy. This is achieved through a dose titration approach over three injection cycles, with a flexible observation period of 12 to 20 weeks post-injection, and a total exposure duration of up to 60 weeks. The clinical relevance of this objective lies in its potential to improve motor function and quality of life in pediatric patients suffering from multifocal spasticity, a common and debilitating condition associated with cerebral palsy.

Secondary objectives include investigating the **safety** of IncobotulinumtoxinA in the same patient population, utilizing a similar dose titration approach over the same duration and observation periods. This aspect is crucial for ensuring that the treatment is not only effective but also safe for long-term use in children.

The clinical trial focuses on evaluating the efficacy of **IncobotulinumtoxinA** in treating **multifocal spasticity of the upper and lower limb due to cerebral palsy** in children. The study population comprises both male and female participants aged 2 to 17 years, all of whom exhibit upper and lower limb spasticity associated with cerebral palsy. Participants are required to have a Gross Motor Function Classification System (GMFCS) level ranging from II to V and must present a focal spasticity score of at least 2 points on the Ashworth scale in the joints related to the selected target clinical pattern. The trial includes both BoNT-A naïve and pretreated children, with the latter having a minimum interval of five months since their last injection. The trial population is considered vulnerable, and informed consent is obtained from parents or legal guardians. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the trial data.

The clinical trial is a **prospective**, open-label, non-randomized, single-arm, dose titration study designed to evaluate the efficacy and safety of **IncobotulinumtoxinA** in children with multifocal spasticity of the upper and lower limbs due to **cerebral palsy**. The trial will involve a total body dose of up to 22U/kg, with a maximum dose of 550U, administered over three injection cycles. The study will include a flexible observation period after each injection, ranging from 12 to 20 weeks, and the total duration of exposure for participants will be up to 60 weeks. The trial is expected to conclude by January 16, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (2 to 17 years), spasticity level, and previous treatment history. Eligible participants will then proceed to baseline visits for each injection cycle, where the primary endpoint will be measured by changes in the Ashworth scale values. Secondary endpoints will include assessments using the Resistance to Passive Movement Scale (REPAS), the Gross Motor Function Classification System (GMFCS), the visual analog scale (VAS), the Goal Attainment Scale (GAS), and the Global Assessment of Efficacy. Safety endpoints will monitor blood pressure, heart rate, respiratory rate, body weight, and adverse events.

Follow-up visits will occur after each injection cycle to evaluate the treatment's efficacy and safety. The end-of-study visit will mark the conclusion of the participant's involvement, summarizing the overall outcomes and any adverse events experienced. Participants are expected to be involved in the study for the entire duration unless conditions arise that necessitate early termination, such as significant adverse reactions or withdrawal of consent. The trial is conducted under a Phase 4 framework, ensuring rigorous evaluation of the treatment's long-term effects and safety profile.

The clinical trial involves the administration of **IncobotulinumtoxinA**, commercially known as XEOMIN, which is a **biological medicine** formulated as a **solution for injection**. The active substance in XEOMIN is **Clostridium botulinum neurotoxin type A (150 kD), free of complexing proteins**. This medication is provided in a powder form for reconstitution into a solution for intramuscular use. The maximum total dose administered during the study is 550 units, with a dose titration approach allowing for a total body dose up to 22U/kg. The treatment is administered over three injection cycles, with a flexible observation period ranging from 12 to 20 weeks, and a total duration of exposure up to 60 weeks. The pharmaceutical form is specifically designed for intramuscular administration, ensuring targeted delivery to the affected muscle groups in children with upper and lower limb spasticity due to cerebral palsy.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the efficacy and safety of IncobotulinumtoxinA in both BoNT-A naïve and pretreated pediatric patients. Participant compliance is monitored throughout the study period to ensure adherence to the dosing schedule and to assess the therapeutic outcomes effectively. The trial is conducted under the sponsorship of Merz Pharmaceuticals GmbH, with the product authorized for use in Italy under the marketing authorization number 038232017.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint involves evaluating changes in the Ashworth scale values between the baseline visits and control visits of each injection cycle. This scale measures the degree of spasticity in patients, providing a quantitative assessment of muscle tone.

Secondary efficacy endpoints include several validated scales and assessments: the Ashworth scale, the Resistance to Passive Movement Scale (REPAS), the Gross Motor Function Classification System (GMFCS), the visual analog scale (VAS), the Goal Attainment Scale (GAS), and the Global Assessment of Efficacy. These tools will be used to provide a comprehensive evaluation of the treatment's impact on spasticity and overall motor function.

The trial will involve a dose titration approach over three injection cycles, with a flexible observation period of 12 to 20 weeks after each injection. The total duration of exposure for participants is up to 60 weeks. Efficacy assessments will be conducted at specified timepoints throughout the study to monitor changes and improvements in the participants' condition.