Lower Limb Spasticity
Conditions
Sponsors
Solstice Neurosciences,LLC, USA, a subsidiary of MDD US Operations LLC, USA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to understand the potential risks and benefits, the study requirements, and provide written informed consent before enrollment into the study; if unable, the subject's Legally Authorized Representative (LAR) may provide written informed consent. 2. Male or female =18 to maximum of 80 years of age, inclusive. 3. Lower limb spasticity due to stroke, traumatic brain injury (TBI), or spinal cord injury that occurred =6 months prior to randomization. Eligible subjects may have lower limb monoplegia or hemiplegia. Subjects with cerebral palsy are eligible for study enrollment. 4. Ambulatory (with or without the use of a walking assistive device). 5. Modified Ashworth Scale (MAS) score =2 in the ankle plantar flexors of the affected lower limb at screening and at baseline. 6. In the Investigator's opinion, the subject will be available and able to comply with the study requirements for at least 1 year, based on the subject's overall health and disease prognosis. 7. In the Investigator's opinion, the subject will be willing and able to comply with all requirements of the protocol, including completion of study questionnaires. A caregiver may be designated to assist with the physical completion of questionnaires/scales. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 232
Exclusion criteria
Exclusion criteria: 1. Quadriplegia/tetraplegia, lower limb diplegia or triplegia 2. Uncontrolled epilepsy or any type of seizure disorder with a seizure(s) within the previous year. 3. Neuromuscular disorders including, but not limited to, amyotrophic lateral sclerosis, primary lateral sclerosis, multiple sclerosis, myasthenia gravis, or muscular dystrophy 4. History of major joint contracture(s), in which, based on Investigator assessment, the contracture(s) significantly contribute to joint immobility in the affected lower limb. 5. Unresolved fracture(s) in the affected lower limb. 6. Severe atrophy in the affected lower limb. 7. Known hypersensitivity to BoNT/ A or BoNT/B or to any MYOBLOC solution components 8. Concomitant use or exposure within 5 half-lives of randomization of the following: aminoglycoside antibiotics, curare-like agents, or other agents that may interfere with neuromuscular function. 9. Treatment with a neurolytic agent (e.g., phenol, alcohol blocks) to the affected lower limb within 1 year before randomization. 10. Presence of a spinal stimulator or intrathecal baclofen pump that has not been turned off within 30 days before screening. 11. Changes to treatment regimen or any new treatment with oral antispasmodics and/or muscle relaxants within 30 days before randomization. 12. Initiation of physical and/or occupational therapy 30 days before randomization must be willing to maintain use of the AFO through Week 4 of the DBP. 14. Prior BoNT/A or BoNT/B treatment in the affected lower limb within 24 weeks before screening. Prior BoNT/A or BoNT/B treatment in areas other than the affected lower limb is not exclusionary but must have occurred at least 12 weeks before screening. Prior toxin exposure must have been well tolerated & without any significant long-term side effects in case of repeated prior exposure. 15. Subjects should not receive nor have any plans to receive any botulinum toxin treatment, other than study drug (MYOBLOC), from the point informed consent is obtained until study participation is complete 16. Severe dysphagia (i.e. inability to swallow liquids, solids/both without choking/medical intervention) or dysphagia with a history of aspiration pneumonia within 6 months before screening 17. Prior surgery to treat spasticity in the affected lower limb (i.e tendon lengthening or tendon transfer). 18. Any anticipated/scheduled surgery during study period with exception of dermatological procedures performed under local anesthesia for purposes of removing precancerous and cancerous lesions. 19. Major surgery within 3 months before screening. 20. Pregnancy/breastfeeding. 21. Females of childbearing potential must agree to use a medically acceptable method of contraception (e.g., intrauterine device, hormonal contraception started at least 1 full cycle before study enrollment or sexual abstinence for duration of study (including 2 months after study completion). For purposes of this study, all females are considered to be of childbearing potential unless they are confirmed by Investigator to be post-menopausal (at least 1 year since last menses, & laboratory test confirmation) biologically sterile, or surgically sterile (e.g.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to assess the efficacy of MYOBLOC versus placebo in the treatment of adult lower limb spasticity.;Secondary Objective: The secondary objectives of this trial are: • To establish a dose response between 2 active doses of MYOBLOC versus placebo. • To assess the duration of therapeutic response after a single administration of MYOBLOC. • To evaluate the long-term safety and tolerability of MYOBLOC after multiple administrations at approximately 13-week intervals over a minimum duration of 1 year.;Primary end point(s): Phase 2 and Phase 3 of the Double-Blind Period: • Change from baseline in tone of the ankle plantar flexors as measured by the MAS at Week 4 post-injection • Clinical Global Impression of Change (CGI-C) in functional ability at Week 4 postinjection;Timepoint(s) of evaluation of this end point: Week 4 post-injection | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy endpoints: Change from baseline at Weeks 2, 8, and 13 and if applicable, at Phase 2 and Phase 3 of the Double-Blind Period Change from baseline at Week 4 post-injection in: •Patient Global Impression of Change (PGI-C) • Caregiver Global Impression of Change (GGI-C) • Pain Numeric Rating Scale (Pain-NRS) • Walking Impairment Questionnaire (WIQ) • Walking and Resting Comfort Scale (WRCS) • Responder rate, defined as the percent of subjects with =1 grade reduction in their MAS score compared to their baseline score at Week 4 in the ankle plantar flexors Change from baseline at Weeks 2, 8, and 13 and if applicable, at reevaluation visits in: • Tone in the ankle plantar flexors as measured by the MAS • Duration of response by measuring the time elapsed between the injection and relapse of spasticity (MAS =2) • CGI-C and Clinical Global Impression of Severity (CGI-S) • PGI-C and Patient Global Impression of Severity (PGI-S) • GGI-C and Caregiver Global Impression of Severity (GGI-S) • Pain Numeric Rating Scale (Pain-NRS) • Walking Impairment Questionnaire (WIQ) • Walking and Resting Comfort Scale (WRCS) Open Label Extension: • Duration of response by measuring the time elapsed between the injection and relapse of spasticity (MAS =2) Exploratory Efficacy Endpoints: Phase 2 and Phase 3 of the Double-Blind Period • Change from baseline at all weeks in tone of the ankle plantar flexors when the baseline MAS was =2 • Responder rate defined as the percent of subjects with a =1 grade reduction in their MAS score at all weeks in the ankle plantar flexors compared to baseline Open-Label Extension Affected lower limb: Change from Day 1 at Weeks 4 and 13 and if applicable, at reevaluation visits of each treatment session in: • Tone in the ankle plantar flexors as measured by the MAS • Tone in any additional muscles selected for injection as measured by the MAS • CGI-C and CGI-S • PGI-C and PGI-S • GGI-C and GGI-S • Pain-NRS • | — |
Countries
Czechia, Czech Republic, Hungary, Poland, Russian Federation, United States
Contacts
Public ContactRegulatory Affairs
Solstice Neurosciences, LLC, USA, a subsidiary of MDD US Operations LLC, USA
Outcome results
None listed