Efficacy and Safety of IncobotulinumtoxinA in Individualized Dosing for Severe Spasticity in Brain Damage-Related Upper and Lower Limb Involvement

The primary objective of this clinical trial is to determine the **efficacy** and **safety** of administering IncobotulinumtoxinA at individualized doses. These doses are selected based on the specific needs of patients with severe **spasticity**, particularly those with involvement of the upper and lower limbs. This is clinically relevant as it aims to optimize treatment outcomes by tailoring the dosage to the patient's unique spasticity patterns, potentially improving functional abilities and quality of life for individuals with brain damage-oriented spasticity.

The clinical trial focuses on individuals diagnosed with **severe multifocal spasticity** of the upper and lower limbs due to acquired brain damage. The study population includes both male and female participants, all of whom are over the age of 18. Participants are required to have no contraindications for treatment with botulinum toxin and must need treatment with IncobotulinumtoxinA at a dose equal to or greater than 800U. The trial does not involve a vulnerable population. Participants must agree to participate in the study and sign the informed consent. They are also required to provide pain assessment data using the VAS scale, muscle tone data using the Ashworth scale, and Barthel scale data during follow-up evaluations. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** and safety of **IncobotulinumtoxinA** in patients with severe spasticity due to acquired brain damage. This study is a randomized, double-blind, controlled trial, with a primary objective to assess the effectiveness of individualized doses of IncobotulinumtoxinA based on the specific needs of patients. The trial is expected to last approximately two years, with an estimated recruitment start date of July 20, 2023, and an estimated end date of July 20, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (over 18 years), diagnosis of severe multifocal spasticity, and the need for a dose of IncobotulinumtoxinA equal to or greater than 800 IU. The inclusion visit will also involve obtaining informed consent and baseline assessments using the Visual Analogue Scale (VAS) for pain, the Ashworth scale for muscle tone, and the Barthel scale for daily living activities.

Following the inclusion visit, participants will receive treatment and attend follow-up visits at 6 and 12 weeks post-injection. These visits will focus on evaluating the primary endpoint, which is the change in the Ashworth scale at 6 weeks, and secondary endpoints, including variations in the VAS scale, effects on the Ashworth scale at 12 weeks, and changes in the Barthel scale. Additionally, patient satisfaction with the treatment and the safety and tolerability of the intervention will be assessed.

The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including the occurrence of any contraindications for treatment with botulinum toxin or withdrawal of consent. The trial aims to provide valuable insights into the tailored use of IncobotulinumtoxinA for managing severe spasticity, contributing to improved patient outcomes and treatment strategies.

The clinical trial involves the administration of **IncobotulinumtoxinA**, commercially known as XEOMIN, which is a **Clostridium botulinum neurotoxin type A (150 kD), free of complexing proteins**. This experimental medication is provided in the form of a powder for solution for injection. The pharmaceutical form is a solution for injection, and it is administered via this route. The dosage is individualized based on the patient's specific needs, with a maximum daily dose of 800 IU and a total maximum dose of 800 IU over the treatment period. The treatment period is defined as 800 days. The medication is manufactured by Merz Pharmaceuticals GmbH and is not a pediatric formulation. Participant compliance with the dosing schedule is monitored throughout the trial.

The study also includes a comparator treatment using **Botulinum toxin type A**. This non-experimental treatment is also provided as a solution for injection and is administered via the same route. The maximum daily dose for this comparator is also 800 IU, with a total maximum dose of 800 IU over a treatment period of 3 weeks. The comparator treatment serves to evaluate the efficacy and safety of the experimental medication against a standard treatment option. Compliance with the administration schedule for the comparator treatment is similarly monitored to ensure adherence to the study protocol.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the effect on the Asworth scale at 6 weeks of treatment, which measures changes in muscle tone. Secondary endpoints include the variation in pain levels as measured by the Visual Analogue Scale (VAS) at 6 and 12 weeks, the effect on the Asworth scale at 12 weeks, and the Barthel scale at 6 and 12 weeks post-injection. Additionally, patient satisfaction with the treatment and the safety and tolerability of the treatment will be evaluated.

Data collection will occur at specified timepoints, including 6 and 12 weeks after treatment initiation. The Asworth scale, VAS scale, and Barthel scale are the tools utilized for these assessments. These scales are validated instruments commonly used in clinical settings to evaluate muscle tone, pain, and daily living activities, respectively. The trial aims to determine the efficacy and safety of **IncobotulinumtoxinA** administered at individualized doses tailored to the specific needs of patients with severe spasticity affecting the upper and lower limbs.