A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults With Upper Limb Spasticity.

NCT04936542 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: CLIN-52120-4522023-509196-16-002021-000161-32
• Study Type: interventional
• Target: 464
• Locations: 4 countries
• Sites: 76

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.

Conditions

Upper Limb Spasticity

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) From Injection to 12 Weeks

  An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A TEAE was defined for each treatment cycle as any AE that occurred during the cycle if it was not present prior to treatment injection, or it was present prior to treatment injection but the intensity increased during the cycle. Percentage of participants with TEAEs that occurred during each cycle from injection to 12 weeks after injection (until 84 days after injection or until the day prior to next injection day or until end of study/early withdrawal day whichever occurred first) is presented. Percentages are rounded off to the tenth decimal place.

  From Baseline (Injection: Day 1) up to 12 weeks

Secondary Outcomes (7)

• Number of Participants With Adverse Drug Reactions (ADRs), Treatment-Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) From Injection to 12 Weeks

  From Baseline (Injection: Day 1) up to 12 weeks

• Adjusted Least Square Mean of Duration of Response Based on Retreatment Criteria

  Baseline (Day 1) up to Week 10 (earliest) if retreatment criteria were met, or up to Week 24 (latest) if retreatment criteria were not met

• Adjusted Least Square Mean of Muscle Tone Assessed by the Modified Ashworth Scale (MAS) for Finger, Wrist and Elbow Flexors Based on Primary Target Muscle Group (PTMG) at Week 12

  Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)

• Adjusted Least Square Mean of Perceived Function and Pain Assessed by the Disability Assessment Scale (DAS) Based on Principal Target of Treatment (PTT) at Week 12

  Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)

• Adjusted Least Square Mean of Physician Global Assessment (PGA) of Treatment Response at Week 12

  Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)

Study Arms (2)

Sequence 1

OTHER

Participants will receive one cycle of aboBoNT-A followed by one cycle of onaBoNT-A in the selected overactive upper limb muscles

Biological: AboBoNT-A; Biological: OnaBoNT-A

Sequence 2

OTHER

Participants will receive one cycle of onaBoNT-A followed by one cycle of aboBoNT-A in the selected overactive upper limb muscles

Biological: AboBoNT-A; Biological: OnaBoNT-A

Interventions

AboBoNT-A BIOLOGICAL

AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL)

Also known as: Dysport®

Sequence 1; Sequence 2

OnaBoNT-A BIOLOGICAL

OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL)

Also known as: Botox®

Sequence 1; Sequence 2

Eligibility Criteria

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

You may qualify if:

• Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent
• a. \[US/France\] 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;
• b. \[Canada\] 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;
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants: Male participants must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception. The participants must agree to use the contraception during the whole period of the study.
• Female participants:A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
• Is a woman of non-childbearing potential, defined as postmenopausal for at least
• year; surgical sterilisation at least 3 months before entering the study; or hysterectomy. or
• Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method during the entire study period.A WOCBP must have a negative highly sensitive pregnancy test at screening (urine or serum) as required by local regulations.

You may not qualify if:

• 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;
• abnormal screening/baseline findings or any other medical condition(s) that, in the opinion of the investigator, might jeopardise the participant's safety
• Women who are pregnant or lactating
• In the clinical judgement of the investigator, BoNT treatment is inappropriate
• BoNT naïve participants with a history of facial neurogenic disorder (facial paralysis, polyradiculoneuropathy) (only for France)
• 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;

Sponsors & Collaborators

• Ipsen: lead

Study Sites (76)

University of Alabama

Birmingham, Alabama, 25233, United States

Location

HonorHealth Scottsdale Osborn Medical Center

Scottsdale, Arizona, 85251, United States

Location

Movement Disorders Center of Arizona

Scottsdale, Arizona, 85258, United States

Location

The University of Arizona

Tucson, Arizona, 85724, United States

Location

Rancho Los Amigos National Rehabilitation Center (RLANRC) - Neurology

Downey, California, 90242, United States

Location

Parkinson's & Movement Disorders Institute

Fountain Valley, California, 92708, United States

Location

Neuro-Pain Medical Center

Fresno, California, 93710, United States

Location

Loma Linda University Health Care

Loma Linda, California, 92350, United States

Location

Southland Neurologic Institute

Long Beach, California, 90808, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Hasbani And Hasbani Medical Group

New Haven, Connecticut, 06511, United States

Location

Ki Health Partners LLC D/B/A New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

First Choice Neurology

Boca Raton, Florida, 33428, United States

Location

James A Haley Veterans Hospital

Tampa, Florida, 33612, United States

Location

University of South Florida Health-Morsani Center for Advanced Healthcare

Tampa, Florida, 33612, United States

Location

Emory University of School of Medicine

Atlanta, Georgia, 30322, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Shirley Ryan Ability Lab

Chicago, Illinois, 60611-3167, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46804, United States

Location

Kansas City Bone and Joint Clinic, P.A. (KCBJ) - Overland Pa

Overland Park, Kansas, 66211-1358, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

LSU Healthcare network

New Orleans, Louisiana, 70112, United States

Location

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, 01655, United States

Location

William Beaumont Hospital

Dearborn, Michigan, 48124, United States

Location

Medical Rehabilitation Group, PC

Grand Blanc, Michigan, 48439, United States

Location

Mary Free Bed Rehabilitation Hospital

Grand Rapids, Michigan, 49503, United States

Location

Beaumont Hospital, Grosse Pointe

Grosse Pointe, Michigan, 48230, United States

Location

Michigan Center of Medical Research

Grosse Pointe, Michigan, 48334, United States

Location

Rusk Rehabilitation Center

Columbia, Missouri, 65203-3248, United States

Location

Wr-Crcn, Llc

Las Vegas, Nevada, 89106, United States

Location

Cooper University Health Care

Cherry Hill, New Jersey, 08003, United States

Location

New York University

New York, New York, 10016, United States

Location

Weill Cornell Medicine Clinical and Translational Science Center

New York, New York, 10065, United States

Location

North Suffolk Neurology

Port Jefferson, New York, 11725, United States

Location

Mayo Clinic

Rochester, New York, 55905, United States

Location

Sunnyview Rehabilitation Hospital

Schenectady, New York, 12308, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Cleveland Clinic - Neurological Institute

Cleveland, Ohio, 44195, United States

Location

MossRehab - Einstein Medical Center

Elkins Park, Pennsylvania, 20010, United States

Location

Penn State Health Physical Medicine and Rehabilitation - Neurology

Hershey, Pennsylvania, 17033, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15213, United States

Location

Aether Medicine

Wayne, Pennsylvania, 19087, United States

Location

Siskin Hospital for Rehabilitation - Neurology

Chattanooga, Tennessee, 37403, United States

Location

The Vanderbilt Clinic

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

TIRR Memorial Hermann Research Center

Houston, Texas, 77030, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Texas Institute for Neurological Disorders

Sherman, Texas, 75093, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Carilion Clinic Institute of Orthopaedics and Neurosciences

Roanoke, Virginia, 24016, United States

Location

MedStar National Rehabilitation Network

Columbia, Washington, 20010, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Lawson Health Research Institute

London, Ontario, N6C 5J1, Canada

Location

Moncton Hospital

Moncton, E1C 6Z8, Canada

Location

Genge Partners

Montreal, H3A 2B4, Canada

Location

Victoria General Hospital

Victoria, V9A 3P2, Canada

Location

Centre Les Capucins

Angers, 49100, France

Location

Hôpital Pellegrin CHU Bordeaux

Bordeaux, 33000, France

Location

Hopital Sud

Échirolles, 38434, France

Location

Hôpital d'Instruction des Armées Laveran

Marseille, 13384, France

Location

Hôpital Saint-Jacques (CHU Nantes)

Nantes, 44000, France

Location

Hopital Archet (CHU de Nice)

Nice, 06202, France

Location

Hopital Fernand Widal

Paris, 75010, France

Location

Centre Mutualiste de Rééducation et de Réadaptation Fonction

Ploemeur, France

Location

Hôpital Jean Bernard (CHU Poitiers)

Poitiers, 86000, France

Location

Hôpital Pontchaillou (CHU Rennes)

Rennes, 35033, France

Location

Pole Saint Helier

Rennes, 35043, France

Location

Centre de Perharidy

Roscoff, 29680, France

Location

Centre Hospitalier de Saint-Amand-les-Eaux

Saint-Amand-les-Eaux, 59230, France

Location

Centre Hospitalier de Saint Amand Montrond

Saint-Amand-Montrond, 18200, France

Location

Hopital Henry Gabrielle (HCL)

Saint-Genis-Laval, 69230, France

Location

Hopitaux Universitaires De Strasbourg

Strasbourg, 67091, France

Location

Hopital de Rangueil

Toulouse, 31059, France

Location

University of Puerto Rico

Santurce, Puerto Rico, 00912, Puerto Rico

Location

Related Publications (2)

• Esquenazi A, Wein TH, Verduzco-Gutierrez M, Ayyoub Z, Page S, Harding S, Maisonobe P, Beneteau M, Patel A; DIRECTION study group. A Phase IV, Randomized, Double-Blind, Crossover Study to Compare the Clinical Safety and Efficacy of AbobotulinumtoxinA and OnabotulinumtoxinA in Adult Upper Limb Spasticity. Adv Ther. 2026 May 20. doi: 10.1007/s12325-026-03635-y. Online ahead of print.

  PMID: 42159955 DERIVED

• 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.

  PMID: 34562231 DERIVED

MeSH Terms

Interventions

abobotulinumtoxinA; onabotulinum toxin A; Botulinum Toxins, Type A

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
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 23, 2021
• Study Start: June 23, 2021
• Primary Completion: August 26, 2025
• Study Completion: August 26, 2025
• Last Updated: July 9, 2026
• Results First Posted: July 9, 2026

Record last verified: 2026-06

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 and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

PR (1); CA (4); US (54); FR (17)