Principal Investigator: Steven Edgley
Keywords: upper limb spasticity , Traumatic Brain Injury , Stroke Department: Physical Medicine & Rehab
IRB Number: 00117316
Specialty: Physical Medicine and Rehabilitation, Physical Medicine and Rehabilitation, Physical Medicine and Rehabilitation, Physical Medicine and Rehabilitation
Sub Specialties: Spasticity Management, Stroke , Mild Brain Injury, Traumatic Brain Injury
Recruitment Status: Recruiting

Contact Information

Heidi Hansen
heidi.hansen@hsc.utah.edu
801.587.2373

Simple Summary

To compare the safety and efficacy of a single treatment of DaxibotulinumtoxinA for Injection (DAXI for injection) at three dose levels (250 U, 375 U, 500 U) versus placebo in reducing muscle tone of adult subjects with upper limb spasticity after stroke or traumatic brain injury.

Detailed Description

A Phase 2, Randomized, Double-Blin, Placebo- Controlled, Parallel Group, Dose-Ranging, Multi-Center Trial to Evaluate the Efficacy and Safety of DaxibotulinumtoxinA for Injection of the Treatment ...

Inclusion Criteria

1. Adults, 18 to 75 years of age.

2. Written informed consent including authorization to release health information.

3. Focal upper limb spasticity (ULS) after a stroke (as defined by WHO criteria) or traumatic brain injury (TBI), last stroke or TBI > 24 weeks prior to Screening.

4. ULS with the primary aggregate pattern (AP): flexed elbow + flexed wrist + clenched fist (flexed fingers) and

≥1 other clinical patterns: adducted and internally rotated shoulder, pronated forearm, and/or thumb-in-palm deformity.

5. Moderate to severe ULS with a MAS score ≥ 2 at the elbow, wrist, and finger flexors; with the exception that the MAS score is ≥ 3 at the suprahypertonic muscle group (SMG) for subjects with previous injections of BoNTA in the paretic limb.

6. Moderate to severe functional disability (DAS score ≥ 2) on the principal target of treatment (1 of 4 functional domains: hygiene, dressing, malposition of the arm/wrist/fingers, and pain).

7. Has sufficient cognitive and communication ability to be able to give informed consent including authorization to release health information.

Exclusion Criteria

1. Upper limb spasticity attributable to an etiology other than stroke or TBI.

2. Bilateral upper limb paresis or quadriplegia.

3. Participated in physiotherapy of the upper extremities ≤ 30 days prior to Screening or planned to start physiotherapy of the upper extremities during the course of the study.

4. Previous treatment with any BoNT or Neurotoxin product for any condition ≤ 16 weeks prior to Screening.

5. Botulinum neurotoxin treatment-experienced subjects who have historically required < 200 U of Botox/Xeomin or its equivalent to effectively treat the upper limb spasticity.

6. Botulinum neurotoxin treatment-experienced subjects who had suboptimal or no treatment response to the most recent BoNTA injection for spasticity, as determined by the investigator; or history of primary or secondary non-response to BoNTA injections, known to have neutralizing antibodies to BoNTA; or have a history of botulinum toxin type B (rimabotulinumtoxinB [Myobloc/Neurobloc]) injection for spasticity due to non-response or suboptimal response to BoNTA.

8. Change in oral medications for spasticity including dosage and dosing frequency ≤ 30 days prior to Screening.

9. Previous or planned treatment of the spastic upper limb with phenol, alcohol injection or surgery.

Profound muscular atrophy or fixed contracture (spasticity angle, per the Tardieu Scale, <10 degrees in the most hypertonic muscle group {elbow, wrist or finger flexors}) of the spastic limb leading to marked limitation on passive range of motion or any other known conditions of the upper limb that could confound muscle tone or functional assessment.

10. Prior treatment with intrathecal baclofen.

11. Any neuromuscular neurological conditions that may place the subject at increased risk of morbidity with exposure to BoNT, including peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional disorders such as Lambert-Eaton syndrome and myasthenia gravis).

12. Use of aminoglycoside antibiotics, polymyxins, lincosamides (e.g., clindamycin), or other agents that might interfere with neuromuscular transmission (e.g., curare-like drugs, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride) ≤ 14 days prior to Screening.

13. Women of child bearing potential (WOCBP), who have a positive pregnancy test at Screening, do not agree to use an effective method of birth control, or plan to become pregnant during the course of the study.

14. Female, who is pregnant or nursing (lactating).

15. Participants in an investigational drug or device study ≤ 30 days prior to Screening.

16. Active skin infections at the injection sites which would put the subject at increased risk of morbidity with BoNT injections.

17. Planned treatment of other conditions (e.g. wrinkles, lower limb spasticity, sialorrhea, over-active bladder, neurogenic detrusor overactivity, cervical dystonia, chronic migraine, and hyperhydrosis) with BoNT during the course of the study.

18. Known to have sensitivity to any component of study medication (Clostridium botulinum toxin type A and/or excipients of DAXI for injection).

19. History of bleeding disorders that are not well-controlled, or on anticoagulation treatment with international normalized ratio (INR) > 3.5 at Screening.

20. History of respiratory symptoms from congestive heart failure, chronic obstructive pulmonary disease, restrictive lung disease, or any unstable pulmonary disease ≤ 30 days prior to Screening.

21. History of Torsade de Pointe, Long QT Syndrome, secondary degree AV block Mobitz type II, or complete heart block.

22. History of severe sialorrhea (Drooling Severity and Frequency Scale score  8), increasing the risk for complications associated with aspiration (e.g. pneumonia, respiratory depression/failure).

23. Body weight of < 54.4 kg.

24. Any acute illnesses or medical conditions including cognitive impairment (e.g., dementia), significant psychiatric illnesses or symptoms (e.g., suicidal ideation, psychosis) that are not stable, and in the investigator’s opinion, could put the subject at increased risk of morbidity, confound the study results, or interfere significantly with the subject’s participation in the study.

Participant Reimbursement

1. Upper limb spasticity attributable to an etiology other than stroke or TBI.2. Bilateral upper limb paresis or quadriplegia.3. Participated in physiotherapy of the upper extremities ≤ 30 days prior to Screening or planned to start physiotherapy of the upper extremities during the course of the study.4. Previous treatment with any BoNT product for any condition ≤ 16 weeks prior to Screening.5. Botulinum neurotoxin treatment-experienced subjects who have historically required < 200 U of Botox/Xeomin or its equivalent to effectively treat the upper limb spasticity.6. Botulinum neurotoxin treatment-experienced subjects who had suboptimal or no treatment response to the most recent BoNTA injection for spasticity, as determined by the investigator; or history of primary or secondary non-response to BoNTA injections, known to have neutralizing antibodies to BoNTA; or have a history of botulinum toxin type B (rimabotulinumtoxinB [Myobloc/Neurobloc]) injection for spasticity due to non-response or suboptimal response to BoNTA.8. Change in oral medications for spasticity including dosage and dosing frequency ≤ 30 days prior to Screening.9. Previous or planned treatment of the spastic upper limb with phenol, alcohol injection or surgery.Profound muscular atrophy or fixed contracture (spasticity angle, per the Tardieu Scale, <10 degrees in the most hypertonic muscle group {elbow, wrist or finger flexors}) of the spastic limb leading to marked limitation on passive range of motion or any other known conditions of the upper limb that could confound muscle tone or functional assessment.10. Prior treatment with intrathecal baclofen.11. Any neuromuscular neurological conditions that may place the subject at increased risk of morbidity with exposure to BoNT, including peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional disorders such as Lambert-Eaton syndrome and myasthenia gravis).12. Use of aminoglycoside antibiotics, polymyxins, lincosamides (e.g., clindamycin), or other agents that might interfere with neuromuscular transmission (e.g., curare-like drugs, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride) ≤ 14 days prior to Screening.13. Women of child bearing potential (WOCBP), who have a positive pregnancy test at Screening, do not agree to use an effective method of birth control, or plan to become pregnant during the course of the study.14. Female, who is pregnant or nursing (lactating).15. Participants in an investigational drug or device study ≤ 30 days prior to Screening.16. Active skin infections at the injection sites which would put the subject at increased risk of morbidity with BoNT injections.17. Planned treatment of other conditions (e.g. wrinkles, lower limb spasticity, sialorrhea, over-active bladder, neurogenic detrusor overactivity, cervical dystonia, chronic migraine, and hyperhydrosis) with BoNT during the course of the study.18. Known to have sensitivity to any component of study medication (Clostridium botulinum toxin type A and/or excipients of DAXI for injection).19. History of bleeding disorders that are not well-controlled, or on anticoagulation treatment with international normalized ratio (INR) > 3.5 at Screening.20. History of respiratory symptoms from congestive heart failure, chronic obstructive pulmonary disease, restrictive lung disease, or any unstable pulmonary disease ≤ 30 days prior to Screening.21. History of Torsade de Pointe, Long QT Syndrome, secondary degree AV block Mobitz type II, or complete heart block.22. History of severe sialorrhea (Drooling Severity and Frequency Scale score  8), increasing the risk for complications associated with aspiration (e.g. pneumonia, respiratory depression/failure).23. Body weight of < 60 kg.24. Any acute illnesses or medical conditions including cognitive impairment (e.g., dementia), significant psychiatric illnesses or symptoms (e.g., suicidal ideation, psychosis) that are not stable, and in the investigator’s opinion, could put the subject at increased risk of morbidity, confound the study results, or interfere significantly with the subject’s participation in the study.