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

• ClinicalTrials.gov Identifier: NCT04936542
• Recruitment Status: Recruiting
• First Posted: June 23, 2021
• Last Update Posted: April 1, 2024
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: June 9, 2021
• First Posted Date: June 23, 2021
• Last Update Posted Date: April 1, 2024
• Actual Study Start Date: June 23, 2021
• Estimated Primary Completion Date: June 28, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 22, 2021): Rate of Treatment-emergent Adverse Events (TEAEs) [ Time Frame: from baseline (injection) to 12 weeks (injection cycle 1 and 2, each cycle is a maximum 24 weeks)) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 22, 2021)

• Rate of Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) [ Time Frame: from baseline (injection) to 12 weeks (injection cycle 1 and 2, each cycle is a maximum 24 weeks)) ]
• Duration of response [ Time Frame: baseline (injection) to retreatment criteria met, from week 10 up to week 24 (for each cycle, 1&2) or baseline to withdrawal or end of study if retreatment criteria not met, up to 24 weeks (for each cycle,1&2, each cycle is a maximum 24 weeks) ]
• Muscle tone assessed by Modified Ashworth scale (MAS) total score [ Time Frame: at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks) ]
  MAS is a scale which represents improvement in spasticity. This tool assesses muscle tone using a six-point scale from 0 = no change to 4 = considerable increase of affected/rigid region.
• Perceived function and pain assessed by the Disability Assessment Scale (DAS) total score [ Time Frame: at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks) ]
  DAS scale to determine the extent of functional impairment in four domains: hygiene, dressing, limb position and pain. Impairment will be assessed on a four-point scale (range 0 to 3, where 0 indicates no disability and 3 indicates severe disability). The four domain ratings will be added to give an overall score between 0 and 12.
• Physician global assessment (PGA) of treatment response [ Time Frame: at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks) ]
  PGA answers will be made on a nine-point rating scale (from -4 = markedly worse, to +4 = markedly improved).
• Change in Quality of Life (QoL) using the SF-12 perceived health score [ Time Frame: at baseline (injection), 4 weeks, 12 weeks and at end of each cycle (injection cycle 1 and 2; each cycle is a maximum 24 weeks) ]
  12-Item Short-form Health Survey (SF-12) is a health survey that will assess general health and wellbeing. The SF-12 summary score is between 0 and 100, with higher scores indicating better self-reported health.
• Change in Quality of Life (QoL) using SQoL-6D [ Time Frame: at baseline (injection), 4 weeks, 12 weeks and at end of each cycle (injection cycle 1 and 2; each cycle is a maximum 24 weeks) ]
  Spasticity-related Quality of Life Tool (SQoL-6D) is a brief questionnaire in six domains (pain/discomfort, involuntary movements or spasms, restricted range of movement, caring for the affected limb, using the affected limb and mobility/balance) using a five-level scale ranging from 0 to 4, with higher scores meaning worse condition.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults With Upper Limb Spasticity.
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Upper Limb Spasticity

Intervention

• Biological: AboBoNT-A
  AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL)
  Other Name: Dysport®
• Biological: OnaBoNT-A
  OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL)
  Other Name: Botox®

Study Arms

• Sequence 1
  Participants will receive one cycle of aboBoNT-A followed by one cycle of onaBoNT-A in the selected overactive upper limb muscles
  Interventions:

  • Biological: AboBoNT-A
  • Biological: OnaBoNT-A
• Sequence 2
  Participants will receive one cycle of onaBoNT-A followed by one cycle of aboBoNT-A in the selected overactive upper limb muscles
  Interventions:

  • Biological: AboBoNT-A
  • Biological: OnaBoNT-A

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 30, 2023): 298
• Original Estimated Enrollment (submitted: June 22, 2021): 564
• Estimated Study Completion Date: June 28, 2025
• Estimated Primary Completion Date: June 28, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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);
• 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;

Exclusion Criteria:

• 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;
• Women who are pregnant or lactating
• 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
• BoNT naïve participants with a history of facial neurogenic disorder (facial paralysis, polyradiculoneuropathy) (only for France).
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ipsen Recruitment Enquiries; see email; clinical.trials@ipsen.com

• Listed Location Countries: Canada, France, Puerto Rico, United States

Administrative Information

• NCT Number: NCT04936542
• Other Study ID Numbers: CLIN-52120-452; 2021-000161-32 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

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.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• 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/).
• URL: https://vivli.org/members/ourmembers/

• Current Responsible Party: Ipsen
• Original Responsible Party: Same as current
• Current Study Sponsor: Ipsen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ipsen Medical Director; Ipsen

• PRS Account: Ipsen
• Verification Date: March 2024