Clinical trial NCT04936542: A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults With Upper Limb Spasticity.
Official title: A Multicentre, Interventional, Post-marketing, Randomised, Double-blind, Crossover Study to Evaluate the Clinical Safety and Efficacy of AbobotulinumtoxinA (Dysport®) in Comparison With OnabotulinumtoxinA (Botox®) When Treating Adults With Upper Limb Spasticity
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Upper Limb Spasticity
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2021-06-23
Enrollment: 464
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is aiming to demonstrate the non-inferiority of AbobotulinumtoxinA (aboBoNT-A) versus OnabotulinumtoxinA (onaBoNT-A) as the primary safety endpoint, and the superiority of aboBoNT-A over onaBoNT-A with respect to duration of response as the key secondary efficacy endpoint when used at optimal doses according to approved prescribing information of each product.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent
* 2a. \[US/France\] Participants with stable Upper Limb Spasticity (ULS) for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study;
* 2b. \[Canada\] Participants with stable post-stroke ULS for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study
* Participants who are either naïve to Botulinum toxin type A (BoNT-A) for ULS or who have been previously treated with BoNT-A for ULS;
* Participants with MAS score of at least 2 at two muscle groups (one of these two muscles groups should be the PTMG) and at least 1 in the remaining muscle group.
* Participants with DAS score of at least 2 on the Principal Target of Treatment (PTT) (one of four functional domains: dressing, hygiene, limb position and pain);
* Participants who require BoNT-A injection in all of the following muscles: flexor carpi radialis, flexor carpi ulnaris, flexor digitorum profundus, flexor digitorum superficialis and biceps brachii;
* Participants for whom injection of a total dose of 900 Units aboBoNT-A or 360 Units onaBoNT-A is considered by the investigator to be clinically appropriate;
* Participants who have been stable for at least 3 months prior to study entry in terms of oral antispasticity, anticoagulant and/or anticholinergic medication if treated are considered by the investigator likely to remain stable for the duration of the study;

Exclusion Criteria:

* Major limitations in the passive range of motion in the paretic upper limb;
* Major neurological impairment (other than limb paresis) that could negatively affect functional performance;
* Participants clinically requiring injection into any upper limb muscles other than the five muscles of one arm listed in Section 5.1, or requiring injection into both arms or any lower limb within the timeframe of the study;
* Hypersensitivity to any BoNT product or excipients;
* Hypersensitivity to cow's milk protein (casein);
* Infection at the proposed injection site(s);
* Known peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g. myasthenia gravis or Lambert-Eaton syndrome);
* Any medical condition (including dysphagia or breathing difficulties/compromised respiratory function) that in the opinion of the investigator, might jeopardize the participant's safety;
* Women who are pregnant or lactating
* Participants treated with BoNT of any type for any indication (e.g. bladder injection, headache or cosmetic) within the previous 12 weeks or planned/likely to be treated during the course of the study;
* Prior history of non-responsiveness to BoNT treatment;
* Previous surgery, or administration of alcohol or phenol in the study limb 6 months or earlier from study enrolment or planned/likely to be treated during the course of the study;
* Participants treated with intrathecal baclofen (except if treatment has reached a stable dose for \>4 weeks and is likely to remain stable throughout the study), aminoglycosides or other agents interfering with neuromuscular transmission (e.g. curare-like agents) within the 4 weeks prior to study enrolment or planned/likely to be treated during the course of the study
* BoNT naïve participants with a history of facial neurogenic disorder (facial paralysis, polyradiculoneuropathy) (only for France).
* Participants receiving concomitant medication treatment with the following PT/OT interventions on the study limb: new splinting/orthotics/casting, serial casting, shockwave therapy, dry needling and needle tenotomies. However, PT/OT interventions not intended to reduce study limb spasticity (e.g. functional training exercises) or with a transient (\<1 day) reduction of study limb spasticity (e.g. stretching, weight bearing) are allowed.

Primary outcomes:
measure: Rate of Treatment-emergent Adverse Events (TEAEs)
timeFrame: from baseline (injection) to 12 weeks (injection cycle 1 and 2, each cycle is a maximum 24 weeks))
Secondary outcomes:
measure: Rate of Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs)
timeFrame: from baseline (injection) to 12 weeks (injection cycle 1 and 2, each cycle is a maximum 24 weeks))
measure: Duration of response
timeFrame: baseline (injection) to retreatment criteria met, from week 10 up to week 24 (for each cycle, 1&2) or baseline to withdrawal or end of study if retreatment criteria not met, up to 24 weeks (for each cycle,1&2, each cycle is a maximum 24 weeks)
measure: Muscle tone assessed by Modified Ashworth scale (MAS) total score
timeFrame: at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks)
measure: Perceived function and pain assessed by the Disability Assessment Scale (DAS) total score
timeFrame: at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks)
measure: Physician global assessment (PGA) of treatment response
timeFrame: at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks)
measure: Change in Quality of Life (QoL) using the SF-12 perceived health score
timeFrame: at baseline (injection), 4 weeks, 12 weeks and at end of each cycle (injection cycle 1 and 2; each cycle is a maximum 24 weeks)
measure: Change in Quality of Life (QoL) using SQoL-6D
timeFrame: at baseline (injection), 4 weeks, 12 weeks and at end of each cycle (injection cycle 1 and 2; each cycle is a maximum 24 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Osborn Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona
state: Arizona
city: Downey
country: United States
facility: Rancho Los Amigos National Rehabilitation Center (RLANRC) - Neurology
state: California
city: Fountain Valley
country: United States
facility: Parkinson's & Movement Disorders Institute
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care
state: California
city: Long Beach
country: United States
facility: Southland Neurologic Institute
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Hasbani And Hasbani Medical Group
state: Connecticut
city: Stamford
country: United States
facility: Ki Health Partners LLC D/B/A New England Institute for Clinical Research
state: Connecticut
city: Boca Raton
country: United States
facility: First Choice Neurology
state: Florida
city: Tampa
country: United States
facility: James A Haley Veterans Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida Health-Morsani Center for Advanced Healthcare
state: Florida
city: Atlanta
country: United States
facility: Emory University of School of Medicine
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Chicago
country: United States
facility: Shirley Ryan Ability Lab
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Bone and Joint Clinic, P.A. (KCBJ) - Overland Pa
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: LSU Healthcare network
state: Louisiana
city: Worcester
country: United States
facility: UMass Memorial Medical Center - University Campus
state: Massachusetts
city: Dearborn
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Grand Blanc
country: United States
facility: Medical Rehabilitation Group, PC
state: Michigan
city: Grand Rapids
country: United States
facility: Mary Free Bed Rehabilitation Hospital
state: Michigan
city: Grosse Pointe
country: United States
facility: Beaumont Hospital, Grosse Pointe
state: Michigan
city: Grosse Pointe
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: Columbia
country: United States
facility: Rusk Rehabilitation Center
state: Missouri
city: Las Vegas
country: United States
facility: Wr-Crcn, Llc
state: Nevada
city: Cherry Hill
country: United States
facility: Cooper University Health Care
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine Clinical and Translational Science Center
state: New York
city: Port Jefferson
country: United States
facility: North Suffolk Neurology
state: New York
city: Rochester
country: United States
facility: Mayo Clinic
state: New York
city: Schenectady
country: United States
facility: Sunnyview Rehabilitation Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic - Neurological Institute
state: Ohio
city: Elkins Park
country: United States
facility: MossRehab - Einstein Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Health Physical Medicine and Rehabilitation - Neurology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Wayne
country: United States
facility: Aether Medicine
state: Pennsylvania
city: Chattanooga
country: United States
facility: Siskin Hospital for Rehabilitation - Neurology
state: Tennessee
city: Nashville
country: United States
facility: The Vanderbilt Clinic
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: TIRR Memorial Hermann Research Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Sherman
country: United States
facility: Texas Institute for Neurological Disorders
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: Roanoke
country: United States
facility: Carilion Clinic Institute of Orthopaedics and Neurosciences
state: Virginia
city: Columbia
country: United States
facility: MedStar National Rehabilitation Network
state: Washington
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital
state: Wisconsin
city: London
country: Canada
facility: Lawson Health Research Institute
state: Ontario
city: Moncton
country: Canada
facility: Moncton Hospital
city: Montréal
country: Canada
facility: Genge Partners
city: Victoria
country: Canada
facility: Victoria General Hospital
city: Angers
country: France
facility: Centre Les Capucins
city: Bordeaux
country: France
facility: Hôpital Pellegrin CHU Bordeaux
city: Echirolles
country: France
facility: Hopital Sud
city: Marseille
country: France
facility: Hôpital d'Instruction des Armées Laveran
city: Nantes
country: France
facility: Hôpital Saint-Jacques (CHU Nantes)
city: Nice
country: France
facility: Hopital Archet (CHU de Nice)
city: Paris
country: France
facility: Hopital Fernand Widal
city: Ploemeur
country: France
facility: Centre Mutualiste de Rééducation et de Réadaptation Fonction
city: Poitiers
country: France
facility: Hôpital Jean Bernard (CHU Poitiers)
city: Rennes
country: France
facility: Hôpital Pontchaillou (CHU Rennes)
city: Rennes
country: France
facility: Pole Saint Helier
city: Roscoff
country: France
facility: Centre de Perharidy
city: Saint-Amand-les-Eaux
country: France
facility: Centre Hospitalier de Saint-Amand-les-Eaux
city: Saint-Amand-Montrond
country: France
facility: Centre Hospitalier de Saint Amand Montrond
city: Saint-Genis-Laval
country: France
facility: Hopital Henry Gabrielle (HCL)
city: Strasbourg
country: France
facility: Hopitaux Universitaires De Strasbourg
city: Toulouse
country: France
facility: Hopital de Rangueil
city: Santurce
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: Esquenazi A, Ayyoub Z, Verduzco-Gutierrez M, Maisonobe P, Otto J, Patel AT. AbobotulinumtoxinA Versus OnabotulinumtoxinA in Adults with Upper Limb Spasticity: A Randomized, Double-Blind, Crossover Study Protocol. Adv Ther. 2021 Nov;38(11):5623-5633. doi: 10.1007/s12325-021-01896-3. Epub 2021 Sep 25.