IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Post-stroke Spasticity of the Upper Limb

Merz Pharmaceuticals GmbH148 enrolled

Overview

IncobotulinumtoxinA (Xeomin) is a botulinum toxin type A preparation free from complexing proteins, i.e. free from proteins other than the active toxin. Injected into the muscle, incobotulinumtoxinA (Xeomin) causes local weakening. Botulinum toxin type A is widely used for treatment of various neurological conditions. This study will investigate the efficacy and safety of incobotulinumtoxinA (Xeomin) in the treatment of post-stroke spasticity of the upper limb.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

148

Conditions

Post-stroke Upper Limb Spasticity

Interventions

IncobotulinumtoxinA (Xeomin)DRUG

incobotulinumtoxinA (Xeomin, also known as "NT 201" or "Botulinum toxin type A (150 kiloDalton), free from complexing proteins") (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), up to five injections in the Open-Label Extension Period, up to 400 units at each injection visit; Mode of administration: intramuscular injection

PlaceboDRUG

Placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Main Inclusion Criteria: * Female or male patients ≥ 18 years * ≥ 6 months since the last stroke, diagnosed by an appropriate health care professional (e.g., neurologist) * Focal spasticity with ≥ 2 points on the Ashworth Scale in the wrist flexors with clinical pattern Flexed Wrist * Focal spasticity with ≥ 2 points on the Ashworth Scale in the fingers flexors with clinical pattern Clenched Fist * For pre-treated patients only: source documentation of the most recent injection session with Botulinum Toxin and sufficient therapeutic response for Flexed Wrist and Clenched Fist * For pre-treated patients only: the most recent injection with Botulinum Toxin must have been maximal 50 Units BOTOX® or 200 Units Dysport® or 2000 Units Neurobloc® (type B preparation) per each of these flexors: carpi ulnaris, digitorum superficialis, digitorum profundus * For pre-treated patients only: the most recent injection with Botulinum Toxin must have been maximal 60 Units BOTOX® or 240 Units Dysport® or 2400 Units Neurobloc® (type B preparation) for flexor carpi radialis Main Exclusion Criteria: * Spasticity of any other origin than stroke * Previous treatment with Botulinum Toxin of any serotype and for any body region within the 4 months prior to Screening (Visit 1, Day -7) * Planned concomitant treatment with Botulinum Toxin of any serotype and for any body region * Previous or planned treatment with phenol- or alcohol-injection in the target limb * Previous surgical treatment of spasticity in the target muscle(s) * Fixed contracture, defined as severe restriction of the range of joint movement on passive stretch * Severe atrophy of the target limb muscles

Locations (3)

Unnamed facility

Czech Republic, Czechia

Unnamed facility

Hungary, Hungary

Unnamed facility

Poland, Poland

Outcomes

Primary Outcomes

Number of Participants With Reduction of at Least 1 Point at Week 4 Compared to Baseline in Ashworth Score in Wrist Flexors

The Ashworth Scale is a well known and commonly used scale in clinical trials with spasticity. It was considered to be the best clinical tool for measuring resistance to movement. It was used to categorize the severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). Subjects with a reduction of one point were defined as responder for the aim of the primary efficacy analysis.

Time frame: Baseline, Week 4

Secondary Outcomes

Responders at Week 4 Based on a Responder Definition of at Least 2 Points Improvement From Baseline in the Ashworth Score for Wrist Flexors

Time frame: Baseline, Week 4

Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Wrist Flexors at All Other Post Baseline Visits

Time frame: Baseline, Week 2, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Data from ClinicalTrials.gov

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Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Elbow Flexors at All Post Baseline Visits

Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Forearm Pronators at All Post Baseline Visits

Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Finger Flexors at All Post Baseline Visits

Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Responders Based on a Responder Definition of at Least 1 Point Improvement From Baseline in the Ashworth Score for Treated Thumb Flexors at All Post Baseline Visits

Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in Ashworth Scale Score for Treated Elbow Flexors

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in Ashworth Scale Score for Treated Elbow Flexors

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in Ashworth Scale Score for Treated Elbow Flexors

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in Ashworth Scale Score for Treated Elbow Flexors

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in Ashworth Scale Score for Treated Elbow Flexors

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in Ashworth Scale Score for Treated Forearm Pronators

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in Ashworth Scale Score for Treated Forearm Pronators

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in Ashworth Scale Score for Treated Forearm Pronators

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in Ashworth Scale Score for Treated Forearm Pronators

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in Ashworth Scale Score for Treated Forearm Pronators

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in Ashworth Scale Score for Wrist Flexors

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in Ashworth Scale Score for Wrist Flexors

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in Ashworth Scale Score for Wrist Flexors

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in Ashworth Scale Score for Wrist Flexors

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in Ashworth Scale Score for Wrist Flexors

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in Ashworth Scale Score for Finger Flexors

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in Ashworth Scale Score for Finger Flexors

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in Ashworth Scale Score for Finger Flexors

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in Ashworth Scale Score for Finger Flexors

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in Ashworth Scale Score for Finger Flexors

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in Ashworth Scale Score for Treated Thumb Flexors

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in Ashworth Scale Score for Treated Thumb Flexors

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in Ashworth Scale Score for Treated Thumb Flexors

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in Ashworth Scale Score for Treated Thumb Flexors

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in Ashworth Scale Score for Treated Thumb Flexors

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Time to Onset of Treatment Effect

Starting with the visit 2 weeks after baseline injection the subject was asked if he/she experienced an treatment effect and if "yes": when. If the subject did not experience an treatment effect he/she was asked again at each of the following visits (at week 4, 8, and 12) of the Main Period until the answer was "yes" or until the final visit of the Main Period was performed. For subjects without any treatment effect the time to onset of effect was censored at the last visit of the Main Period.

Time frame: Period starting at Visit 2 (baseline injection) of the Main Period up to onset of treatment effect

Time to Waning of Treatment Effect

Subject who reported an onset of treatment effect were asked at each visit/telephone contact starting at week 4 at earliest if he/she felt that there was a waning of the treatment effect. The same question was asked at each of the following telephone contacts and visits (up to the Final Visit of the Main Period) if the answer at the respective previous visit was "no". If the patient answered with "yes" he/she will be asked at which week after the injection (= the time span in weeks) the waning of effect occurred. For all subjects without an onset of treatment effect the waning was set to zero.

Time frame: Defined as time (weeks) from Visit 2 (injection session at Baseline, Day 0) to the subjective estimation of the waning of the effect

Duration of Treatment Effect

The duration of treatment effect is defined as the time period from the day of injection until the time point of a need for a new injection agreed by the patient and the investigator. For subjects without any treatment effect the duration of effect was set to zero.

Time frame: Period from the day of injection until the time point of a need for a new injection agreed by the patient and the investigator

Investigator's Global Assessment of Efficacy

The Investigator's Global Assessment of Efficacy is a subjective estimation assessed on a 4-point Likert scale with the items 1=very good, 2=good, 3=moderate, and 4=poor.

Time frame: Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Patient's Global Assessment of Efficacy

The Patient's Global Assessment of Efficacy is a subjective estimation assessed on a 4-point Likert scale with the items 1=very good, 2=good, 3=moderate, and 4=poor.

Time frame: Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Carer's Global Assessment of Efficacy

The Carer's Global Assessment of Efficacy is a subjective estimation assessed on a 4-point Likert scale with the items 1=very good, 2=good, 3=moderate, and 4=poor.

Time frame: Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in the Disability Assessment Scale for the Principal Therapeutic Target

The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability).

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in the Disability Assessment Scale for the Principal Therapeutic Target

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in the Disability Assessment Scale for the Principal Therapeutic Target

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in the Disability Assessment Scale for the Principal Therapeutic Target

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Disability Assessment Scale for the Principal Therapeutic Target

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Hygiene"

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Hygiene"

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Hygiene"

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Hygiene"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Hygiene"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Dressing"

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Dressing"

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Dressing"

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Dressing"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Dressing"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Limb Position"

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Limb Position"

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Limb Position"

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Limb Position"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Limb Position"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 2 in the Disability Assessment Scale for Domain "Pain"

Time frame: Baseline, Week 2

Change From Baseline to Week 4 in the Disability Assessment Scale for Domain "Pain"

Time frame: Baseline, Week 4

Change From Baseline to Week 8 in the Disability Assessment Scale for Domain "Pain"

Time frame: Baseline, Week 8

Change From Baseline to Week 12 in the Disability Assessment Scale for Domain "Pain"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Disability Assessment Scale for Domain "Pain"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Cleaning the Palm of the Affected Hand"

The Carer Burden Scale evaluates the impact of antispastic medication on the physical burden of the carer. It consists of the following items: A=cleaning the palm of the affected hand; B=cutting the fingernails of the affected hand; C=Cleaning the armpit of the affected arm; D=putting the affected arm through the sleeve; E=applying a splint on the affected arm. Each item was assessed on a 5-point Likert scale which values ranges from 0 (=no difficulty) to 4 (=cannot do the task).

Time frame: Baseline, Week 4

Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Cleaning the Palm of the Affected Hand"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Cleaning the Palm of the Affected Hand"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Cutting the Fingernails of the Affected Hand"

Time frame: Baseline, Week 4

Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Cutting the Fingernails of the Affected Hand"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Cutting the Fingernails of the Affected Hand"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Cleaning the Armpit of the Affected Arm"

Time frame: Baseline, Week 4

Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Cleaning the Armpit of the Affected Arm"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Cleaning the Armpit of the Affected Arm"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Putting the Affected Arm Through the Sleeve (e.g., Coat, Shirt, Jacket)"

Time frame: Baseline, Week 4

Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Putting the Affected Arm Through the Sleeve (e.g., Coat, Shirt, Jacket)"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Putting the Affected Arm Through the Sleeve (e.g., Coat, Shirt, Jacket)"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)

Change From Baseline to Week 4 in the Carer Burden Scale for Domain "Applying a Splint on the Affected Arm"

Time frame: Baseline, Week 4

Change From Baseline to Week 12 in the Carer Burden Scale for Domain "Applying a Splint on the Affected Arm"

Time frame: Baseline, Week 12

Change From Baseline to Final Visit in the Carer Burden Scale for Domain "Applying a Splint on the Affected Arm"

Time frame: Baseline, Final Visit of the Main Period (to be performed at week 12 after 1st injection at earliest, at week 20 at latest)