Upper Limb SpasticityPhase 4DIRECTIONNCT04936542
A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults With Upper Limb Spasticity.
A Phase 4 study testing AboBoNT-A and OnaBoNT-A in people with Upper Limb Spasticity, run by Ipsen at 76 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Upper Limb Spasticity
- What is being tested?
- AboBoNT-A and OnaBoNT-A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 464 participants
- Where
- 76 sitesin 4 countries
- Study dates
- 23 Jun 2021to 26 Aug 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
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- 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
- 1 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.
Who cannot join
- 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);
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- 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;
- 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
- 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.
- Participants previously randomised for this study
- Participants unwilling or unable to understand the nature, scope and possible consequences of the study and to comply with study procedures and requirements
- Participants currently enrolled in any other clinical study or have participated in one within the 12 weeks (or 5 half-lives of the investigational product of that study, whichever is longer) prior to enrolment/inclusion visit, or are scheduled to receive a new investigational drug while the study is ongoing
Trial locations and contacts
76 sites in 4 countries.
76 sites in 4 countries
United States54 sites
Emory University of School of Medicine
Atlanta, Georgia, 30322
University of Alabama
Birmingham, Alabama, 25233
First Choice Neurology
Boca Raton, Florida, 33428
Siskin Hospital for Rehabilitation - Neurology
Chattanooga, Tennessee, 37403
Cooper University Health Care
Cherry Hill, New Jersey, 08003
Shirley Ryan Ability Lab
Chicago, Illinois, 60611-3167
Cleveland Clinic - Neurological Institute
Cleveland, Ohio, 44195
Rusk Rehabilitation Center
Columbia, Missouri, 65203-3248
MedStar National Rehabilitation Network
Columbia, Washington, 20010
University of Texas Southwestern
Dallas, Texas, 75390
William Beaumont Hospital
Dearborn, Michigan, 48124
Rancho Los Amigos National Rehabilitation Center (RLANRC) - Neurology
Downey, California, 90242
MossRehab - Einstein Medical Center
Elkins Park, Pennsylvania, 20010
Fort Wayne Neurological Center
Fort Wayne, Indiana, 46804
Parkinson's & Movement Disorders Institute
Fountain Valley, California, 92708
Neuro-Pain Medical Center
Fresno, California, 93710
Medical Rehabilitation Group, PC
Grand Blanc, Michigan, 48439
Mary Free Bed Rehabilitation Hospital
Grand Rapids, Michigan, 49503
Beaumont Hospital, Grosse Pointe
Grosse Pointe, Michigan, 48230
Michigan Center of Medical Research
Grosse Pointe, Michigan, 48334
Penn State Health Physical Medicine and Rehabilitation - Neurology
Hershey, Pennsylvania, 17033
Hawaii Pacific Neuroscience
Honolulu, Hawaii, 96817
TIRR Memorial Hermann Research Center
Houston, Texas, 77030
Wr-Crcn, Llc
Las Vegas, Nevada, 89106
Loma Linda University Health Care
Loma Linda, California, 92350
Southland Neurologic Institute
Long Beach, California, 90808
University of California Los Angeles
Los Angeles, California, 90095
University of Louisville
Louisville, Kentucky, 40202
Medical College of Wisconsin - Froedtert Hospital
Milwaukee, Wisconsin, 53226
The Vanderbilt Clinic
Nashville, Tennessee, 37232
Hasbani And Hasbani Medical Group
New Haven, Connecticut, 06511
LSU Healthcare network
New Orleans, Louisiana, 70112
New York University
New York, New York, 10016
Weill Cornell Medicine Clinical and Translational Science Center
New York, New York, 10065
Kansas City Bone and Joint Clinic, P.A. (KCBJ) - Overland Pa
Overland Park, Kansas, 66211-1358
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, 15213
North Suffolk Neurology
Port Jefferson, New York, 11725
Carilion Clinic Institute of Orthopaedics and Neurosciences
Roanoke, Virginia, 24016
Mayo Clinic
Rochester, New York, 55905
University of Utah School of Medicine
Salt Lake City, Utah, 84132
UT Health San Antonio
San Antonio, Texas, 78229
Sunnyview Rehabilitation Hospital
Schenectady, New York, 12308
HonorHealth Scottsdale Osborn Medical Center
Scottsdale, Arizona, 85251
Movement Disorders Center of Arizona
Scottsdale, Arizona, 85258
Swedish Neuroscience Institute
Seattle, Washington, 98122
Texas Institute for Neurological Disorders
Sherman, Texas, 75093
Ki Health Partners LLC D/B/A New England Institute for Clinical Research
Stamford, Connecticut, 06905
Stony Brook University Medical Center
Stony Brook, New York, 11794
James A Haley Veterans Hospital
Tampa, Florida, 33612
University of South Florida Health-Morsani Center for Advanced Healthcare
Tampa, Florida, 33612
Montefiore Medical Center
The Bronx, New York, 10467
The University of Arizona
Tucson, Arizona, 85724
Aether Medicine
Wayne, Pennsylvania, 19087
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
France17 sites
Centre Les Capucins
Angers, 49100
Hôpital Pellegrin CHU Bordeaux
Bordeaux, 33000
Hopital Sud
Échirolles, 38434
Hôpital d'Instruction des Armées Laveran
Marseille, 13384
Hôpital Saint-Jacques (CHU Nantes)
Nantes, 44000
Hopital Archet (CHU de Nice)
Nice, 06202
Hopital Fernand Widal
Paris, 75010
Centre Mutualiste de Rééducation et de Réadaptation Fonction
Ploemeur
Hôpital Jean Bernard (CHU Poitiers)
Poitiers, 86000
Hôpital Pontchaillou (CHU Rennes)
Rennes, 35033
Pole Saint Helier
Rennes, 35043
Centre de Perharidy
Roscoff, 29680
Centre Hospitalier de Saint-Amand-les-Eaux
Saint-Amand-les-Eaux, 59230
Centre Hospitalier de Saint Amand Montrond
Saint-Amand-Montrond, 18200
Hopital Henry Gabrielle (HCL)
Saint-Genis-Laval, 69230
Hopitaux Universitaires De Strasbourg
Strasbourg, 67091
Hopital de Rangueil
Toulouse, 31059
Canada4 sites
Lawson Health Research Institute
London, Ontario, N6C 5J1
Moncton Hospital
Moncton, E1C 6Z8
Genge Partners
Montreal, H3A 2B4
Victoria General Hospital
Victoria, V9A 3P2
About this study
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
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
- Being tested
- AboBoNT-A, OnaBoNT-A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AboBoNT-ABiological
Also called Dysport®
AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL)
OnaBoNT-ABiological
Also called Botox®
OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: AboBoNT-A; Biological: OnaBoNT-A |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
AE: any untoward medical occurrence in a clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via an authorized medicinal product, or any other medically important event. TEAE for each treatment cycle: any AE that occurred during cycle if it was not present prior to treatment injection, or it was present prior to treatment injection but intensity increased during cycle. ADR: any TEAE that was assessed by Investigator as related to study treatment. AESI: TEAE that suggested a possible remote spread of toxin or events suggestive of hypersensitivity like reactions.
Measured: From Baseline (Injection: Day 1) up to 12 weeks
Adjusted Least Square Mean of Duration of Response Based on Retreatment Criteria
The duration of response was defined for Cycle 1 as time between Cycle 1 injection and the first Cycle 1 visit when retreatment criteria were met (from Week 10 visit), or time between Cycle 1 injection and study withdrawal if the participant discontinued from the study before Cycle 2 injection without meeting retreatment criteria; for Cycle 2 as time between Cycle 2 injection and the first Cycle 2 visit when retreatment criteria were met (from Week 10 visit), or time between Cycle 2 injection and end of study if the participant completed the study or discontinued from the study after Cycle 2 injection without meeting retreatment criteria. It was calculated as the date of retreatment criteria met or withdrawal date (or last visit date for lost to follow-up participants) or completion date - date of injection + 1.
Measured: 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
Muscle tone for finger, wrist, elbow flexors assessed with MAS tool using scale: 0= no increase in muscle tone, 1= slight increase in muscle tone, manifested by a catch and release or by minimal resistance at end of range of motion (ROM) when affected part(s) was moved in flexion or extension, 1+= slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout remainder of ROM, 2= more marked increase in muscle tone through most of ROM, but affected part(s) easily moved, 3= considerable increase in muscle tone, passive movement difficult, 4= affected part(s) rigid in flexion or extension. PTMG included finger, wrist or elbow flexors which were selected by Investigators at screening as muscle group with highest MAS score. MAS total score was calculated as the sum of scores for all 3 joints (finger, wrist, elbow), ranged from: 0 (best) to 12 (worst); higher scores indicated worse outcomes.
Measured: 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
The DAS was used to determine the extent of functional impairment in 4 domains: hygiene, dressing, limb position and pain. Impairment was assessed on a 4-point scale: 0= no disability, 1= mild disability (noticeable but did not interfere significantly with normal activities), 2= moderate disability (normal activities required increased effort and/or assistance) and 3= severe disability (normal activities limited). The 4 domain ratings were added to obtain DAS total score which ranged between 0 (best) and 12 (worst); higher scores indicated severe disability. The PTT was defined at screening as 1 of the 4 domains, with an associated DAS score for assessment.
Measured: 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
The PGA of treatment response was assessed by asking the Investigator the following question: 'how would you rate the response to treatment in the participant's upper limb since the last injection?' and answered on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). Higher scores indicate greater better outcomes. 'Any improvement' in PGA was defined by a score including: +1, +2, +3 and +4.
Measured: Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Change From Baseline to Weeks 4, 12 and 24 (End of Cycle) in Quality of Life (QoL) Assessed by the 12-Item Short Form (SF-12) Health Survey Perceived Health Score: Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) Scores
SF-12 consisted of 12 questions \& asked respondent to answer questions as they pertained to way he/she felt or acted during past week. SF-12 covered 8 domains of health:physical functioning(PF),role physical(RP),bodily pain(BP),general health(GH),vitality(VT),social functioning(SF),role emotional(RE) \& mental health(MH). Score range for each of 8 domains:0(maximum disability) to 100(no disability);higher scores:good QoL. Responses on SF-12 were used to obtain 2 summary scores:PCS-12 contributed by PF,RP,BP, and GH and MCS-12 contributed by MH,RE,SF and VT. Summations of item scores of same domains gave sub-scale scores,which were transformed to obtain summary scores of PCS-12 \& MCS-12. Both PCS-12 \& MCS-12 scores ranged from 0(worst) to 100(best);higher scores:better QoL.Baseline:last non-missing measurement prior to first study treatment administration.Change from baseline in QoL assessed by SF-12 health survey perceived health score based on PCS-12 and MCS-12 scores is presented.
Measured: Baseline (Day 1) and Weeks 4, 12, and 24 (end of cycle) (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Change From Baseline to Weeks 4, 12 and 24 (End of Cycle) in Quality of Life Assessed by the Spasticity-Related Quality of Life Tool (SQoL-6D)
The SQoL-6D questionnaire was a brief questionnaire in 6 domains: pain/discomfort, involuntary movements or spasms, restricted range of movement, caring for the affected limb, using the affected limb and mobility/balance which was designed to assess QoL in relation to spasticity that affected the upper limb, which included the arm, shoulder or hand. Each dimension was assessed by asking participants about symptoms within the last 7 days, using a 5-level scale ranging from 0 (best) to 4 (worst); higher scores indicated worse condition. The mean of the 6-dimension scores was calculated to obtain the total score which ranged from 0 (worse) to 100 (best); higher score indicated better QoL. Baseline was defined as the last non-missing measurement prior to first study treatment administration. Change from Baseline in QoL assessed by SQoL-6D is presented.
Measured: Baseline (Day 1) and Weeks 4, 12, and 24 (end of Cycle) (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2021
- Study start23 Jun 2021
- Primary completion26 Aug 2025
- Study completion26 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Upper Limb SpasticityStudies of the same condition, open and under way.
- More trials run by IpsenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 464 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ipsen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04936542
- Sponsor's protocol ID
- CLIN-52120-452
- Other IDs
- 2023-509196-16-00, 2021-000161-32, 2023
- Acronym
- DIRECTION
- Status last verified
- Jun 2026
- First submitted
- 9 Jun 2021
- Last updated
- 9 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.
Publications
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 Aug;43(8):3451-3472. doi: 10.1007/s12325-026-03635-y. Epub 2026 May 20.
PubMed 42159955Esquenazi 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.
PubMed 34562231
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04936542
- Acronym / sponsor ID
- DIRECTION / CLIN-52120-452
- Conditions
- Upper Limb Spasticity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 464 participants (actual)
- Lead sponsor
- IpsenIndustry (pharma, biotech, devices)
- Study start
- 23 Jun 2021 (actual)
- Primary completion
- 26 Aug 2025 (actual)
- Study completion
- 26 Aug 2025 (actual)
- First posted
- 23 Jun 2021 (actual)
- Results
- Posted 9 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Other | Biological: AboBoNT-A, Biological: OnaBoNT-AParticipants will receive one cycle of aboBoNT-A followed by one cycle of onaBoNT-A in the selected overactive upper limb muscles |
| Sequence 2 | Other | Biological: AboBoNT-A, Biological: OnaBoNT-AParticipants will receive one cycle of onaBoNT-A followed by one cycle of aboBoNT-A in the selected overactive upper limb muscles |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (20 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AboBoNT-AAlso: Dysport®AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL) | Biological | Sequence 1, Sequence 2 |
| OnaBoNT-AAlso: Botox®OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL) | Biological | Sequence 1, Sequence 2 |
Primary outcome
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) From Injection to 12 Weeks
Time frame: From Baseline (Injection: Day 1) up 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.
7 secondary outcomes
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
Time frame: From Baseline (Injection: Day 1) up to 12 weeks
Adjusted Least Square Mean of Duration of Response Based on Retreatment Criteria
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 12 (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Change From Baseline to Weeks 4, 12 and 24 (End of Cycle) in Quality of Life (QoL) Assessed by the 12-Item Short Form (SF-12) Health Survey Perceived Health Score: Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) Scores
Time frame: Baseline (Day 1) and Weeks 4, 12, and 24 (end of cycle) (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Change From Baseline to Weeks 4, 12 and 24 (End of Cycle) in Quality of Life Assessed by the Spasticity-Related Quality of Life Tool (SQoL-6D)
Time frame: Baseline (Day 1) and Weeks 4, 12, and 24 (end of Cycle) (Cycles 1 and 2; each cycle was 12 to 24 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42159955Esquenazi 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 Aug;43(8):3451-3472. doi: 10.1007/s12325-026-03635-y. Epub 2026 May 20.
- Derived from this study: PubMed 34562231Esquenazi 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.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ipsen Medical Director study director
Ipsen
76 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing AboBoNT-A and OnaBoNT-A in people with Upper Limb Spasticity, run by Ipsen at 76 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 76 sites in United States, France, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) From Injection to 12 Weeks (time frame: From Baseline (Injection: Day 1) up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04936542, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.