A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Treatment Efficacy and Safety Study of MYOBLOC® in the Treatment of Adult Lower Limb Spasticity
Overview
- Phase
- Phase 2
- Intervention
- Phase 2; High Dose MYOBLOC
- Conditions
- Spasticity
- Sponsor
- Supernus Pharmaceuticals, Inc.
- Enrollment
- 272
- Locations
- 9
- Primary Endpoint
- The Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3]
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
Phase 2/3, randomized, double-blind, placebo-controlled, single-treatment, multicenter trial assessing the efficacy and safety of MYOBLOC for the treatment of lower limb spasticity, in adults followed by an open-label extension safety trial.
Detailed Description
Phase 2, randomized, double-blind, placebo-controlled, single-treatment, multicenter trial will compare the efficacy and safety of two doses of MYOBLOC versus volume-matched placebo in the treatment of lower limb spasticity in adults. An interim analysis will evaluate all available safety and efficacy data from the Phase 2 double-blind trial in order to recommend which dose will be evaluated in subsequent Phase 3 trial. The Phase 3, randomized, double-blind, placebo-controlled, single-treatment, multicenter trial will compare the efficacy and safety of MYOBLOC versus placebo in the treatment of lower limb spasticity in adults. Subjects who complete either the Phase 2 or Phase 3 trial will continue into an open-label extension where each will receive 5 separate MYOBLOC treatments (\~13 week apart) for lower limb spasticity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to understand the potential risks and benefits, the study requirements, and provide written informed consent before enrollment into the study; or if unable, the subject's Legally Authorized Representative (LAR) may provide written informed consent.
- •Male or female ≥18 to maximum of 80 years of age, inclusive.
- •Lower limb spasticity due to stroke, traumatic brain injury, 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.
- •Ambulatory (with or without the use of a walking assistive device).
- •Modified Ashworth Scale (MAS) score ≥2 in the ankle plantar flexors of the affected lower limb at screening and at baseline.
- •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.
- •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.
Exclusion Criteria
- •Quadriplegia/tetraplegia, lower limb diplegia or triplegia.
- •Uncontrolled epilepsy or any type of seizure disorder with a seizure(s) within the previous year.
- •Neuromuscular disorders including, but not limited to, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), multiple sclerosis (MS), myasthenia gravis, or muscular dystrophy.
- •History of major joint contracture(s), in which, based on the Investigator's assessment, the contracture(s) significantly contribute(s) to joint immobility in the affected lower limb.
- •Unresolved fracture(s) in the affected lower limb.
- •Severe atrophy in the affected lower limb.
- •Known hypersensitivity to botulinum toxins type A or B or to any MYOBLOC solution components.
- •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.
- •Treatment with a neurolytic agent (e.g., phenol, alcohol blocks) to the affected lower limb within 1 year before randomization.
- •Presence of a spinal stimulator or intrathecal baclofen pump that has not been turned off within 30 days before screening.
Arms & Interventions
Phase 2; High Dose MYOBLOC
High Dose MYOBLOC is a single treatment and will be compared to volume-matched placebo
Intervention: Phase 2; High Dose MYOBLOC
Phase 2; Low Dose MYOBLOC
Low Dose MYOBLOC is a single treatment and will be compared to volume-matched placebo
Intervention: Phase 2; Low Dose MYOBLOC
Phase 2; Placebo
Volume-matched placebo is a single treatment
Intervention: Phase 2; Placebo
Phase 3; MYOBLOC
MYOBLOC is a single treatment and will be compared to volume-matched placebo
Intervention: Phase 3; MYOBLOC
Phase 3; Placebo
Volume-matched placebo is a single treatment
Intervention: Phase 3; Placebo
Outcomes
Primary Outcomes
The Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3]
Time Frame: Baseline and Week 4
The first co-primary endpoint is the change from baseline in the Modified Ashworth Scale (MAS) score in the tone of the ankle plantar flexors at Week 4 post-injection. The MAS is an internationally accepted and validated instrument used to measure resistance during passive soft-tissue stretching. Resistance will be measured and recorded using a 6-point scale ranging from 0 (no increase in muscle tone) to 4 (affected part\[s\] rigid in flexion or extension). A lower change from baseline MAS score (\<0) represents a better outcome.
The Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) in functional ability [Phase 2 and Phase 3]
Time Frame: Week 4
The second co-primary endpoint is the Clinical Global Impression of Change (CGI-C) score in functional ability at Week 4 post-injection. The CGI-C scale is a single item clinician assessment of how much the patient's functional ability has improved, worsened or has not changed relative to the patient's baseline state prior to treatment (injection). The CGI-C is rated on a 7-point Likert scale from 1 to 7, where 1 = "Very much improved", 2 = "Much improved", 3 = "Minimally improved", 4 = "No change", 5 = "Minimally worse", 6 = "Much worse", and 7 = "Very much worse". Successful therapy is indicated by a lower score (\<4) in subsequent testing.
Secondary Outcomes
- Effect of MYOBLOC on the Patient Global Impression of Change (PGI-C) [Phase 2 and Phase 3](Weeks 2, 8, 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Caregiver Global Impression of Change (GGI-C) [Phase 2 and Phase 3](Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Numeric Rating Scale of Pain (Pain-NRS) [Phase 2 and Phase 3](Baseline and Week 4)
- Effect of MYOBLOC on the Walking Impairment Questionnaire (WIQ) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on Walking and Resting Comfort Scale (WRCS) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on Modified Ashworth Scale (MAS) Responder Rate Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3](Baseline and Week 4)
- The Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- The Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) in functional ability [Phase 2 and Phase 3](Weeks 2, 8, and13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Clinical Global Impression of Severity (CGI-S) [Phase 2 and Phase 3](Baseline and Weeks 2, 4, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Patient Global Impression of Severity (PGI-S) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Caregiver Global Impression of Severity (GGI-S) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))
- Effect of MYOBLOC on the Pain Numeric Rating Scale (Pain-NRS) [Phase 2 and Phase 3](Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit))