Safety of Xeomin for Lower Limb Spasticity in Multiple Sclerosis Patients

March 21, 2017 updated by: Multiple Sclerosis Center of Northeastern New York

A Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Incobotulinumtoxin Type A for the Functional Improvement of Lower Extremity Spasticity in Patients With Multiple Sclerosis

The purpose of this study is to determine if Xeomin® will prove effective for significantly improving lower extremity spasticity and will be well tolerated by the majority of MS patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Overall Design: Thirty patients with MS, male or female, ages 18-70, either relapsing or progressive types, are to be evaluated in a prospective treatment trial comparing gait before and after injections of Xeomin.

Patient Population: The patients included are to have functionally significant equinovarus spasticity in primarily one lower extremity; functionally significant spasticity is defined as spasticity impairing gait during observation of during a 25 foot walk, causing falls, or leading to secondary orthopedic complications such as genu recurvatum or pain in the low back or hip. The patients are to be ambulatory, with stable disease.

Dose Selection: A dose of 200 units to 400 units of Xeomin will be injected by EMG-guided technique into the appropriate muscles in the effected leg. These muscles may include gastrocnemius and soleus, tibialis posterior or other muscles as determined by the examiner. The dose administered will be determined by the blinded injector based on determination of muscle bulk and the degree of spasticity Blinding: Investigators will be blinded to medication used throughout study. Site will randomize subjects in a 1:1 fashion by using an unblinded site delegate.

Compliance with Laws and Regulations: This study will be conducted in accordance with the U.S. Food and Drug Administration (FDA) regulations, the International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice (GCP), and applicable local, state, and federal laws.

Study Assessments: After informed consent is obtained and screening measurements are completed, the patients will return at 4 weeks for injection for primary and secondary efficacy evaluations. Additional evaluations at 6 and 12 weeks will be made in order to determine the duration of effect of Xeomin for secondary efficacy evaluations.

Concomitant therapy includes any prescription or over the counter preparations being taken by the patient at any time from screening through the last study visit. All concomitant medications should be reported to the investigator and recorded.

Patients enrolled in the study will be permitted to take all medication with the exception of the following

  • Methylprednisolone within 30 days prior to screening
  • Injection of any botulinum toxin within the past 6 months (180days)

During the study patients will be permitted to receive any treatment deemed necessary by the investigator for the management of disease. However patients requiring commencement of excluded therapies will be discontinued from the study and the data will not be used for statistical purposes.

Study Assessments:

Patients must sign informed consent form before any screening evaluations or measurements are performed. Patients must satisfy all of the inclusion criteria and none of the exclusion criteria to be randomized. Information regarding consented patients who are not subsequently randomized will be keep in the regulatory binder.

SAFETY MEASURES

Safety assessments will consist of monitoring and recording adverse events (AE's) and serious adverse events (SAE's). All SAE's will be reported to the FDA Med Watch within 48 business hrs of site notification of such SAE. For this protocol a serious SAE will be defined as any AE that is meets any of the following criteria:

  • Fatal (i.e. the AE actually causes or leads to death)
  • Life threatening (i.e. the AE in the view of the investigator, placing the patient at immediate risk of death)
  • Requires or prolongs hospitalization
  • Results in persistent or significant disability/incapacity (i.e. the AE results in substantial disruption to the patients ability to conduct normal life functions)
  • A congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product
  • Considered a significant medical event by the investigator (e.g, may jeopardize the patient or may require medical/surgical intervention to prevent one of the outcomes listed above)

The FDA Adverse Event Reporting System Med Watch is a Reporting system for Health Professionals

STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE A detailed description of the statistical methodology will be provided in the statistical analysis plan (SAP) which may deviate from the analysis outlined in the protocol; however, any substantial deviations from the protocol will be detailed in a protocol amendment.

Description of Endpoints

  • Primary Endpoint Mean change from injection visit to week 6 in the Modified Ashworth score between Xeomin vs placebo group

  • Secondary Endpoints

    • Mean change from injection visit to week 6 in Multiple Sclerosis Impact Scale (MSIS-29) Physical and psychological scores between Xeomin vs placebo group
    • Mean change from injection visit to week 6 in T25FW between Xeomin vs Placebo group.
    • Patient global impression of change (PGIC) between Xeomin vs placebo group
    • Clinical Global Impression of change between Xeomin vs placebo group
    • Mean change from injection visit to week 6 in Likert pain scale between Xeomin vs placebo group
    • Mean change from injection visit to week 6 in MSWS-12 between Xeomin vs placebo group.

Demography and Baseline Disease Characteristics

  • Demographic and baseline characteristics will be presented descriptively (i.e., mean, standard deviation, median, range) and analyzed with appropriate statistical methods given the distribution and type of data.

Efficacy

  • Analysis Population The Intent-to-Treat population is defined as all subjects who receive at least 1 dose of study treatment and who provide efficacy assessment.
  • General Methods of Analysis Descriptive statistics will be provided for all efficacy endpoints. A two-sided test, p-value and confidence interval will be presented for analysis in general.
  • Primary Endpoint Analysis The primary endpoint is the mean change from injection visit to week 6 in Modified Ashworth score . A two sample T-test will be used to compare the treatment difference between Xeomin and placebo group. If the data is not normally distributed, Wilcoxon's rank sum test will be used for the analysis.
  • Secondary Endpoints Analysis Percent change from injection visit to week 6 will be calculated for the primary endpoint. It will be analyzed similarly as that for the primary endpoint. For secondary endpoints MSIS 29, T25FW, Likert pain scale and MSWS-12 a similar statistical approach as outlined for the primary endpoint will be used to assess the mean changes from injection visit to week 6 in each of the scales between treatment groups.

Patient global impression of change (PGIC) and clinical global Impression of change will be analyzed using the Wilcoxon's rank sum test.

Safety

  • Analysis Population The safety population is defined as all subjects who receive at least 1 dose of study treatment.

Adverse events will be listed. Serious AE will be listed as well.

Sample Size Considerations Based on observational study, patients using Xeomin had an improvement of 50% on the Ashworth scale. A sample size of 15 patients per group will provide 80% power to detect a treatment difference of 50% with a 0.05 two-sided significance level using a chi-square test.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Latham, New York, United States, 12110
        • Multiple Sclerosis Center of Northeastern New York

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female patients with clinically definite MS, either RRMS or a progressive form (SPMS, PPSM, PRMS)
  • Ages 18-65 years.
  • Patients must be in a stable state, with no clinical relapses or methylprednisolone treatments in the last 30 days, or have slowly progressive MS, with an EDSS score of 2.0-6.5.
  • Patients must have functionally significant spasticity in predominantly one lower extremity as determined by a score of >2 on the Modified Ashworth Scale at screen

Exclusion Criteria:

  • Unstable medical or neurological disease
  • Known sensitivity to Xeomin
  • Prior injection with any botulinum toxin within 6 months
  • EDSS score of 7.0 or greater
  • Exacerbation of MS within the past 30 days
  • Significant cognitive impairment or psychiatric disease
  • Advanced arthritis or any other cause of clinically significant limitation of passive range of motion around any of the joints being assessed in the study.
  • Concomitant neurologic conditions causing spasticity or rigidity.
  • Has had major surgery within 3 months prior to Screening visit that may affect spasticity assessments such as back, lower leg or knee surgeries.
  • Use of medications that could influence muscle tone or any anti-spasticity medications must be stable >90 days prior to screening visit and must remain stable throughout study period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: incabotulinumtoxinA
intramuscular injection, 200 to 400 units, 1 injection visit only
Biological: incabotulinumtoxinA
A dose of 200 units to 400 units of Xeomin will be injected by EMG-guided technique into the appropriate muscles in the effected leg at injection visit
Other Names:
  • Xeomin®
PLACEBO_COMPARATOR: Placebo
intramuscular injection, saline 200 - 400 units , 1 injection visit only
Biological: Placebo
Saline injection on the day of injection visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Mean change from injection visit to week 6 in the Modified Ashworth score between Xeomin vs placebo group
Time Frame: injection visit to week 6
injection visit to week 6

Secondary Outcome Measures

Outcome Measure
Time Frame
Mean change from injection visit to week 6 in Multiple Sclerosis Walking Scale (MSWS-12) between Xeomin vs placebo group
Time Frame: from injection visit to week 6
from injection visit to week 6
Change in Patient Global impression of change between Xeomin vs placebo group
Time Frame: change between week 6 and week 12
change between week 6 and week 12
Mean change from injection visit to week 6 in Multiple Sclerosis Impact Scale (MSIS-29) physical and psychological scores between Xeomin vs placebo group
Time Frame: injection visit to week 6
injection visit to week 6
Mean change from injection visit to week 6 in Timed 25 Foot Walk (T25FW) between Xeomin vs placebo group
Time Frame: injection visit to week 6
injection visit to week 6
Clinical Global impression of change between Xeomin vs placebo group
Time Frame: change between week 6 and week 12
change between week 6 and week 12
Mean change from injection visit to week 6 in Likert Pain Scale between Xeomin vs placebo group
Time Frame: injection visit to week 6
injection visit to week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Multiple Sclerosis Center of Northeastern New York

Collaborators

Merz North America, Inc.

Investigators

  • Principal Investigator: Keith R Edwards, MD, MS Center of Northeastern New York

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (ACTUAL)

January 27, 2016

Study Completion (ACTUAL)

December 31, 2016

Study Registration Dates

First Submitted

October 21, 2013

First Submitted That Met QC Criteria

October 21, 2013

First Posted (ESTIMATE)

October 24, 2013

Study Record Updates

Last Update Posted (ACTUAL)

March 22, 2017

Last Update Submitted That Met QC Criteria

March 21, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPASTICITY-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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