Clinical trial NCT02969356: Study to Evaluate Effects of DYSPORT® Injected in Lower and Upper Limb Combined With Guided Self-Rehabilitation Contract (GSC)
Official title: An International, Multicentre, Prospective, Single-Arm Study to Assess the Effect on Voluntary Movements of AbobotulinumtoxinA 1500 U Administered in Both Upper and Lower Limbs in Conjunction With a Guided Self-Rehabilitation Contract in Adult Subjects With Spastic Hemiparesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Spastic Hemiparesis
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2016-11-21
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical study is to assess whether AbobotulinumtoxinA (Dysport®) injections in upper and lower limbs accompanied with a personal exercise plan called "Guided Self-rehabilitation Contract" (GSC) can improve voluntary movements in subjects with hemiparesis.


Eligibility criteria: Inclusion Criteria:

* Subjects aged at least the national legal adult age.
* Subjects with hemiparesis due to acquired brain injury (ABI) presenting with muscle overactivity impeding motor function based on investigator's judgement including, but not limited to, at least one of the following requiring botulinum neurotoxin (BoNT) treatment: typical clenched fist; flexed wrist; flexed elbow; or plantar flexed foot pattern.
* At least 12 months since the ABI (i.e. stroke or traumatic brain injury (TBI)).
* Naïve or non-naïve to BoNT treatment; if non-naïve, at least 4 months after the last BoNT injection, of any serotype.
* Upper limb active function with an overall score between 2 and 7, as assessed by Modified Frenchay Scale (MFS), if the primary TT limb is the upper limb (UL).
* A 10-metre maximal WS barefoot between 0.2 and 1.4 m/s, if the primary TT limb is the lower limb (LL). Maximal WS barefoot will be performed without walking aids. However, a cane may be permitted if absolutely necessary (although this may prevent detection of treatment-induced improvements). In this case, the same aid will have to be used for all WS assessments during the study.
* Subjects must provide written informed consent to participate in the study prior to any study-related procedures.
* Female subjects of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study until the last visit of the subjects and for at least 12 weeks post injection. Acceptable methods of contraception include total abstinence, male partner has had a vasectomy, double barrier method (e.g. male condom plus spermicide, or female diaphragm plus spermicide), intrauterine device, or hormonal contraceptive (oral, transdermal, implanted and injected).
* Subjects must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow-up evaluation as specified in the protocol

Exclusion Criteria:

* Inability to understand protocol procedures and requirements, which, in the opinion of the investigator, could negatively impact on protocol compliance, in particularly inability to exercise according to the GSC.
* Previous surgery on the affected muscles and ligaments, tendons, nerve trunks, or bones of the treated upper or lower limb.
* Previous treatment with phenol and/or alcohol in any of the treated limbs any time before the study.
* Any medical condition (including severe dysphagia or breathing difficulties) that may increase, in the opinion of the investigator, the likelihood of adverse events (AEs) related to BoNT A treatment.
* Current, planned or received within the last 4 weeks prior to study treatment, treatment with any drug that interferes either directly or indirectly with neuromuscular function (for example, aminoglycosides).
* Major neurological impairment other than spastic paresis (including major proprioceptive ataxia or apraxia on the paretic side) that could negatively impact on the functional performance of the subject.
* Known disease of the neuromuscular junction (such as Lambert-Eaton myasthenic syndrome or myasthenia gravis).
* Known sensitivity to BoNT-A or any excipient of Dysport.
* Infection at the injection site(s).
* Current pregnancy or lactation. A pregnancy test will be performed at the start of the study for all female subjects of childbearing potential (i.e. not surgically sterile or 2 years postmenopausal).
* Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
* Abnormal baseline findings or any other medical condition(s) that, in the opinion of the investigator, might jeopardise the subject's safety.
* Subjects treated, or likely to be treated, with intrathecal baclofen during the course of the study or during the 4 weeks before study entry.
* Subjects who have participated in any therapeutic clinical study/received any investigational agent within 30 days of enrolment.

Primary outcomes:
measure: Percentage of Responder Participants at Week 6 After the Second Injection, According to Composite Active Range of Motion (AROM) in the Primary TT Limb
timeFrame: At Week 6, Cycle 2
Secondary outcomes:
measure: Percentage of Responder Participants at Week 6 After the First Injection, According to Composite AROM in the Primary TT Limb
timeFrame: At Week 6, Cycle 1
measure: Mean Change From Baseline in AROM Against 10 Prespecified Muscle Groups at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
timeFrame: Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit
measure: Mean Change From Baseline in Composite AROM Against Injected Muscle Groups (Any of the 10 Prespecified Muscles) at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
timeFrame: Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit
measure: Mean Change From Baseline in Full Composite AROM Against 5 UL or 5 LL Muscle Groups, Regardless of Whether the Muscle Groups Were Injected or Not at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
timeFrame: Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit
measure: Mean Change From Baseline in Modified Frenchay Scale (MFS) Overall Score Evaluated Locally and Centrally at Week 12 of Each Treatment Cycle and Last Study Visit
timeFrame: Week 12 of each treatment cycle and last study visit
measure: Mean Change From Baseline in Maximal Walking Speed Barefoot at Week 12 of Each Treatment Cycle and at Last Study Visit
timeFrame: Week 12 of each treatment cycle and last study visit
measure: Participant Satisfaction With the GSC at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
timeFrame: At baseline (for participants who had GSC previously only), Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit
measure: Change From Baseline in Participant's Beliefs That the GSC Will Help to Improve Functional Capacity at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
timeFrame: Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit
measure: Change From Baseline in Physiotherapist's Beliefs That the GSC Will Help to Improve Functional Capacity at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
timeFrame: Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit
measure: Percentage of Days Over Study Period When GSC Therapy Was Performed
timeFrame: From baseline to end of the study, up to 280 days
measure: Global Assessment of Benefits of the Study Therapy
timeFrame: At reinjection cycle visit (Week 12, 16 or 20) and last study visit (Week 24 or 40)
measure: Number of Participants Satisfied With a Longer Interval Between 2 Treatment Cycles
timeFrame: At reinjection cycle visit (Week 16 or 20) and last study visit (Week 24 or 40)
measure: Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Scores at Last Study Visit
timeFrame: At last study visit (Week 24 or 40)
measure: Change From Baseline in Short Form 12 (SF-12) Scales at Last Study Visit
timeFrame: At last study visit (Week 24 or 40)
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Kansas Institute of Research, Kansas City Bone & Joint Clinic, Division of Signature Medical Group of KC
state: Kansas
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, Physical Medicine and Rehabilitation
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Department of Neurology, Division of Movement Disorders, Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: UT Health Physical Medicine & Rehabilitation Department, TIRR Memorial Hermann
state: Texas
city: Brno
country: Czechia
facility: Fakultní nemocnice Královské Vinohrady, Neurologická klinika
city: Brno
country: Czechia
facility: Neurology and Physiotherapy Outpatient Clinic
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno Neurologická klinika
city: Pardubice
country: Czechia
facility: Neurology Department - Regional Hospital Pardubice
city: Praha
country: Czechia
facility: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague
city: Créteil
country: France
facility: Service de Médecine Physique et Réadaptation, Hôpital Albert-Chenevier
state: Cedex
city: Bordeaux
country: France
facility: Service de Médecine Physique et de Réadaptation, Bâtiment Tastet-Girard, Groupe Hospitalier Pellegrin
city: Reims
country: France
facility: Service de Médecine Physique et Réadaptation, Hôpital Sébastopol - CHU de Reims
city: Saint-Étienne
country: France
facility: Service de Médecine Physique et Réadaptation, CHU Saint Etienne - Hôpital Bellevue
city: Krasnoyarsk
country: Russian Federation
facility: Federal Siberian Scientific Clinical Center
city: Moscow
country: Russian Federation
facility: Medical Rehabilitation Center
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg Bekhterev Psychoneurological Research Institute
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hospital n.a. V.D.Seredavin
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: Gracies JM, Francisco GE, Jech R, Khatkova S, Rios CD, Maisonobe P; ENGAGE Study Group. Guided Self-rehabilitation Contracts Combined With AbobotulinumtoxinA in Adults With Spastic Paresis. J Neurol Phys Ther. 2021 Jul 1;45(3):203-213. doi: 10.1097/NPT.0000000000000359.