Dysport® Adult Lower Limb Spasticity Follow-on Study

NCT01251367 | Completed Phase 3 Results

• 2 other identifiers: Y-55-52120-1422009-017723-26
• Study Type: interventional
• Target: 352
• Locations: 11 countries
• Sites: 50

Brief Summary

The purpose of this research study is to assess the long term safety of Dysport® in hemiparetic subjects with lower limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles.

Conditions

Post-stroke Spasticity; Spasticity Post-Traumatic Brain Injury

Outcome Measures

Primary Outcomes (14)

• Assessment of the Long-Term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)

  Adverse events (AEs) were monitored from the time that the subject gave informed consent to the end of the study/early withdrawal (EOS/EW). An AE was reported as a TEAE if it was not present prior to study treatment administration in Study 140, or if it was present prior to study treatment in Study 140 but the intensity increased during the treatment phase of this study. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any AE that was assessed as a hypersensitivity reaction. TEAEs, treatment related TEAEs, severe TEAEs, TEAEs leading to death, TEAEs leading to withdrawal, treatment emergent AESIs, and serious adverse events (SAEs) are summarised by treatment cycle.

  Up to EOS (maximum duration of 52 weeks).

• Mean Change From Baseline to Week 4 in Systolic and Diastolic Blood Pressure (BP)

  Systolic and diastolic BP were recorded at baseline and at each subsequent study visit. BP was measured with the subject in a sitting position after resting for 3 minutes. Mean change in BP from baseline at Week 4 is reported per cycle.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Heart Rate (HR)

  HR was recorded at baseline and at each subsequent study visit. HR was measured with the subject in a sitting position after resting for 3 minutes. Mean change in HR from baseline at Week 4 is reported per cycle.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Red Blood Cell (RBC) Count

  Blood samples for RBC count were taken at baseline, at Week 4, and at EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)

  Blood samples for haemoglobin and MCHC were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Haematocrit

  Blood samples for haematocrit were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Mean Corpuscular Haemoglobin (MCH)

  Blood samples for MCH were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Mean Corpuscular Volume (MCV)

  Blood samples for MCV were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets

  Blood samples for WBC count with differentials (neutrophils, lymphocytes) and platelet count were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)

  Blood samples were taken at baseline, at Week 4, and at the EOS/EW for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Total Bilirubin and Creatinine

  Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at Week 4, and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose

  Blood samples for analysis of BUN and fasting blood glucose levels were taken at baseline, at Week 4 and at the EOS/EW. Outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

• Presence of Botulinum Toxin Type A (BTX-A) Neutralising Putative Antibodies (NAbs) Following Injection of Dysport®

  Blood samples were collected at baseline, Week 4 and at EOS/EW to test for the presence of BTX-A antibodies. The number of subjects who were either NAb positive at baseline or negative at baseline but then positive following injection of Dysport® were reported.

  At Week 4

• Mean Change From Baseline to Week 4 in 12-Lead Electrocardiogram (ECG)

  12-lead ECG tracing was performed at baseline, at Week 4 of each cycle and at EOS/EW. The 12-lead ECG recordings were performed at a paper speed of 25 millimetres/second (mm/s), recorded with the subject in a supine position after 5 minutes rest. The ECG parameters; QT Duration, QT interval corrected with Fridericia's method (QTcF), QT interval corrected with Bazett's method (QTcB), QRS duration and PR duration were recorded and outcome measure is reported per cycle as change from baseline at Week 4.

  Baseline and Week 4 of each cycle

Secondary Outcomes (18)

• Mean Change From Baseline to Week 4 in the Modified Ashworth Scale (MAS) Score Measured in the Gastrocnemius-soleus Complex (GSC) (Knee Extended)

  Baseline and Week 4 of each cycle

• Mean Change From Baseline to Week 4 in the MAS Measured in the Soleus Muscle (Knee Flexed)

  Baseline and Week 4 of each cycle

• Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the GSC (Knee Extended) at Week 4

  Week 4 of each cycle

• Percentage of Subjects With At Least a 1 or 2 Grade Reduction in the MAS Measured in the Soleus Muscle (Knee Flexed) at Week 4

  Week 4 of each cycle

• Physician's Global Assessment (PGA) of Treatment Response at Week 4

  Week 4 of each cycle

Study Arms (1)

Dysport®

EXPERIMENTAL

Dysport® is injected into lower limbs across 4 cycles of treatment, a minimum of 12 weeks between 2 injections. Doses vary from 1000 U to 1500 U.

Biological: Botulinum toxin type A

Interventions

Botulinum toxin type A BIOLOGICAL

I.M. (intramuscular) injection on day 1 of each treatment cycle.

Also known as: AbobotulinumtoxinA (Dysport®)

Dysport®

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completion of Dysport® Adult Lower Limb Spasticity Double Blind study Y-55-52120-140 (NCT01249404)

You may not qualify if:

• Fixed contractures in lower limb

Sponsors & Collaborators

• Ipsen: lead

Study Sites (50)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Rancho Los Amigos

Downey, California, 90242, United States

Location

Pacific Neuroscience Medical Group

Oxnard, California, 93030, United States

Location

Associated Neurologist of Southern CT, PC

Fairfield, Connecticut, 06824, United States

Location

Design Neuroscience Center

Miami, Florida, 33136, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Island Neurological Associates

Plainview, New York, 11803, United States

Location

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7200, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Moss Rehab & Albert Einstein

Elkins Park, Pennsylvania, 19027, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

The University of Texas Southwestern Medical Center at Dalla

Dallas, Texas, 75390-9016, United States

Location

University of North Texas HSC at Ben Hogan Center

Fort Worth, Texas, 76104, United States

Location

University of Texas - Houston

Houston, Texas, 77030, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

St George Hospital

Kogarah, Australia

Location

Epworth Rehabilitation

Melbourne, Australia

Location

Royal Melbourne Hospital

Melbourne, Australia

Location

St Vincent's Hospital

Melbourne, Australia

Location

St Vincent's Hospital

Sydney, Australia

Location

Westmead Hospital

Sydney, Australia

Location

Université catholique de Louvain av Hippocrate 10

Brussels, Belgium

Location

Clinique Universitaire

Yvoir, Belgium

Location

Charles University in Prague

Prague, Czechia

Location

CHU Jean MINJOZ

Besançon, France

Location

Centre de Réadaptation de Coubert

Coubert, France

Location

Centre Hospitalier Albert Chenevier-Hopital Henri Mondor

Créteil, France

Location

Hopital Raymond Poincarré

Garches, France

Location

Hôpital de L'Archet I

Nice, France

Location

Hôpital Sébastopol

Reims, France

Location

Hôpital Civil

Strasbourg, France

Location

Hopital Rangueil

Toulouse, France

Location

National Institute for Medical Rehabilitation

Budapest, Hungary

Location

Uno Medical Trials

Budapest, Hungary

Location

Petz Aladar Country Hospital

Győr, Hungary

Location

Azienda Ospedaliero Universitaria "Policlinico Vittorio Emanuele"

Catania, Italy

Location

Specjalistyczna Praktyka Lekarska

Katowice, Poland

Location

Centrum Medyczne Plejady

Krakow, Poland

Location

Krakowska Akademia Neurologii Sp. z o.o.

Krakow, Poland

Location

Malopolskie Centrum Medyczne

Krakow, Poland

Location

Nzoz Neuro - Card

Poznan, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Poland

Location

Serviço de Reabilitação

Alcabideche, Portugal

Location

Centro Hospitalar Lisboa Norte

Lisbon, Portugal

Location

Centro Hospitalar São João

Porto, Portugal

Location

Medical Rehabilitation Center

Moscow, Russia

Location

Scientific Research Institute of Neurology

Moscow, Russia

Location

State University

Saint Petersburg, Russia

Location

Derer's Hospital

Bratislava, Slovakia

Location

Univerzitna nemocnica Bratislava

Bratislava, Slovakia

Location

Related Publications (4)

• Esquenazi A, Brashear A, Deltombe T, Rudzinska-Bar M, Krawczyk M, Skoromets A, O'Dell MW, Grandoulier AS, Vilain C, Picaut P, Gracies JM. The Effect of Repeated abobotulinumtoxinA (Dysport(R)) Injections on Walking Velocity in Persons with Spastic Hemiparesis Caused by Stroke or Traumatic Brain Injury. PM R. 2021 May;13(5):488-495. doi: 10.1002/pmrj.12459. Epub 2020 Sep 11.

  PMID: 32741133 DERIVED

• Esquenazi A, Stoquart G, Hedera P, Jacinto LJ, Dimanico U, Constant-Boyer F, Brashear A, Grandoulier AS, Vilain C, Picaut P, Gracies JM. Efficacy and Safety of AbobotulinumtoxinA for the Treatment of Hemiparesis in Adults with Lower Limb Spasticity Previously Treated With Other Botulinum Toxins: A Secondary Analysis of a Randomized Controlled Trial. PM R. 2020 Sep;12(9):853-860. doi: 10.1002/pmrj.12348. Epub 2020 Mar 27.

  PMID: 32108436 DERIVED

• McAllister PJ, Khatkova SE, Faux SG, Picaut P, Raymond R, Gracies JM. Effects on walking of simultaneous upper/lower limb abobotulinumtoxina injections in patients with stroke or brain injury with spastic hemiparesis. J Rehabil Med. 2019 Oct 29;51(10):813-816. doi: 10.2340/16501977-2604.

  PMID: 31529136 DERIVED

• Gracies JM, Esquenazi A, Brashear A, Banach M, Kocer S, Jech R, Khatkova S, Benetin J, Vecchio M, McAllister P, Ilkowski J, Ochudlo S, Catus F, Grandoulier AS, Vilain C, Picaut P; International AbobotulinumtoxinA Adult Lower Limb Spasticity Study Group. Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension. Neurology. 2017 Nov 28;89(22):2245-2253. doi: 10.1212/WNL.0000000000004687. Epub 2017 Nov 1.

  PMID: 29093068 DERIVED

MeSH Terms

Interventions

Botulinum Toxins, Type A; abobotulinumtoxinA

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Limitations and Caveats

Data is summarised according to total dose received at each corresponding cycle (i.e. including 1000 U and 1500 U Dysport® in lower limb during all cycles, as well as 1000 U in lower limb + 500 U Dysport® in upper limb during Cycles 3 and 4).

Results Point of Contact

• Title: Medical Director, Neurology,
• Organization: Ipsen

clinical.trials@ipsen.com

Study Officials

• Ipsen Study Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2010
• First Posted: December 1, 2010
• Study Start: June 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: September 28, 2022
• Results First Posted: November 9, 2017

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Locations

RU (3); SL (2); PT (3); FR (8); PL (6); CZ (1); IT (1); HU (3); AU (6); US (15); BE (2)