Dysport® Adult Upper Limb Spasticity Extension Study

NCT01313312 | Completed Phase 3 Results DMC

• 2 other identifiers: Y-52-52120-1482010-019162-83
• Study Type: interventional
• Target: 258
• Locations: 9 countries
• Sites: 34

Brief Summary

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

Conditions

Nervous System Disorders

Outcome Measures

Primary Outcomes (15)

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

  A TEAE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any adverse event (AE) that was assessed as a hypersensitivity reaction. TEAEs, AESIs, severe TEAEs, serious adverse events (SAEs), treatment related TEAEs, TEAEs leading to withdrawal and fatal SAEs are summarised by treatment cycle.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Diastolic and Systolic Blood Pressure (BP)

  Systolic and diastolic BP were recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Heart Rate (HR)

  HR was recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Red Blood Cell (RBC) Count

  Blood samples for RBC count were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)

  Blood samples for haemoglobin and MCHC were taken at baseline, at post treatment follow up visit Week 4, and at the end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Haematocrit

  Blood samples for haematocrit were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Haemoglobin (MCH)

  Blood samples for MCH were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Volume (MCV)

  Blood samples for MCV were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal 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 post treatment follow up visit Week 4, and at end of study or early withdrawal.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)

  12-lead ECG tracing was performed at baseline, post treatment at Week 4 and at the end of study/early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest. The ECG parameters reported were QRS duration, PR duration, QT duration, QTcB (QT interval corrected for HR according to Bazett), and QTcF (QT interval corrected for HR according to Fridericia) at baseline and the change to end of study/early withdrawal visit (EOS).

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)

  Blood samples for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in Total Bilirubin and Creatinine

  Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal 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 post treatment follow up visit Week 4, and at end of study/early withdrawal.

  Up to Week 52

• Mean Change From Baseline to End of Study/Early Withdrawal in 12 Lead ECG - HR

  HR was measured by 12-lead ECG tracing, performed at baseline, at post treatment follow up visit Week 4, and at the end of study or early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest.

  Up to Week 52

• Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies

  Blood samples were collected at baseline, Week 4 of each cycle, and at the end of study/early withdrawal to test for the presence of Botulinum Toxin A Binding antibodies. Samples positive for the presence of binding antibodies were then analysed for the presence of neutralising putative antibodies. The number of subjects who were either positive (+ve) or negative (-ve) at baseline and then positive post baseline for binding or neutralising antibodies were reported.

  Up to Week 52

Secondary Outcomes (26)

• Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4

  At Week 4

• Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG

  At Week 4

• Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4

  At Week 4

• Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4

  At Week 4

• Mean Change From Baseline MAS in the Wrist Flexors at Week 4

  At Week 4

Study Arms (1)

Total Dysport®

EXPERIMENTAL

A total of 254 subjects in the open label study received between 1 and 5 intramuscular (i.m) injections of Dysport® according to their individual needs, for a period of up to 12 months. All subjects were administered an appropriate dosage of Dysport® (1000 Units \[U\] or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response. From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.

Biological: Botulinum toxin type A

Interventions

Botulinum toxin type A BIOLOGICAL

Dysport® was supplied to the study centres in vials containing 500 U of botulinum toxin type A (BTX-A). Depending on the dose administered up to 3 vials were required for the injection. Each vial was reconstituted with sodium chloride for injection (0.9%). A total volume of 5.0 mL of the reconstituted product was injected for Dysport® 500 U and 1000 U, and 7.5 mL was injected for Dysport® 1500 U.

Also known as: AbobotulinumtoxinA (Dysport®)

Total 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 the double blind study, Y-52-52120-145

You may not qualify if:

• Major limitation in the passive range of motion in upper limb

Sponsors & Collaborators

• Ipsen: lead

Study Sites (34)

Rancho Los Amigos National Rehabilitation Center

Downey, California, 90242, United States

Location

Associated Neurologist of Southern CT, PT

Fairfield, Connecticut, 06824, United States

Location

Parkinson's Disease & Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33488, United States

Location

Design Neuroscience Miami

South Miami, Florida, 33143, United States

Location

The Rehabilitation Institute of Chicago

Chicago, Illinois, 60611, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029-6574, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Univ of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Southwestern Medical Center at Dallas University of Texas

Dallas, Texas, 75390, United States

Location

University of North Texas HSC at Ben Hogan Center

Fort Worth, Texas, 76104, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Université catholique de Louvain av Hippocrate 10

Brussels, Belgium

Location

Clinique Universitaire

Yvoir, Belgium

Location

Charles University in Prague

Prague, Czechia

Location

CHU Brest

Brest, 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 Sébastopol

Reims, France

Location

CHU Strasbourg

Strasbourg, France

Location

Hopital Rangueil

Toulouse, France

Location

Petz Aladar County Hospital

Gyor, Budapest, Hungary

Location

National Institute for Medical Rehabilitation

Budapest, Hungary

Location

Azienda Hospedaliero

Catania, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Malopolskie Centrum Medyczne

Krakow, Poland

Location

Krakowska Akademia Neurologii

Warsaw, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Poland

Location

Medical Rehabilitation Center

Moscow, Russia

Location

Scientific Center of Neurology of RAMS

Moscow, Russia

Location

State University

Saint Petersburg, Russia

Location

Derer's Hospital

Bratislava, Slovakia

Location

Related Publications (1)

• Delafont B, Carroll K, Vilain C, Pham E. Investigation of mixed model repeated measures analyses and non-linear random coefficient models in the context of long-term efficacy data. Pharm Stat. 2018 Sep;17(5):515-526. doi: 10.1002/pst.1868. Epub 2018 May 20.

  PMID: 29781237 DERIVED

MeSH Terms

Conditions

Nervous System Diseases

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

Results Point of Contact

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

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: March 10, 2011
• First Posted: March 11, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 28, 2022
• Results First Posted: June 7, 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

HU (2); BE (2); IT (2); SL (1); FR (7); US (13); CZ (1); PL (3); RU (3)