Efficacy and Safety Study of MYOBLOC® in the Treatment of Adult Lower Limb Spasticity

NCT04099667 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: SN-SPAS-202
• Study Type: interventional
• Target: 272
• Locations: 2 countries
• Sites: 9

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.

Conditions

Spasticity

Keywords

Stroke; Traumatic Brain Injury (TBI); Monoplegia; Hemiplegia; Lower limb

Outcome Measures

Primary Outcomes (2)

• The Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for Tone of the Ankle Plantar Flexors [Phase 2 and Phase 3]

  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.

  Baseline and Week 4

• The Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) in functional ability [Phase 2 and Phase 3]

  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.

  Week 4

Secondary Outcomes (16)

• Effect of MYOBLOC on the Patient Global Impression of Change (PGI-C) [Phase 2 and Phase 3]

  Baseline and Week 4

• Effect of MYOBLOC on the Caregiver Global Impression of Change (GGI-C) [Phase 2 and Phase 3]

  Week 4

• 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 Week 4

• Effect of MYOBLOC on Walking and Resting Comfort Scale (WRCS) [Phase 2 and Phase 3]

  Baseline and Week 4

Study Arms (5)

Phase 2; Low Dose MYOBLOC

EXPERIMENTAL

Low Dose MYOBLOC is a single treatment and will be compared to volume-matched placebo

Drug: Phase 2; Low Dose MYOBLOC

Phase 2; High Dose MYOBLOC

EXPERIMENTAL

High Dose MYOBLOC is a single treatment and will be compared to volume-matched placebo

Drug: Phase 2; High Dose MYOBLOC

Phase 2; Placebo

PLACEBO COMPARATOR

Volume-matched placebo is a single treatment

Drug: Phase 2; Placebo

Phase 3; MYOBLOC

EXPERIMENTAL

MYOBLOC is a single treatment and will be compared to volume-matched placebo

Drug: Phase 3; MYOBLOC

Phase 3; Placebo

PLACEBO COMPARATOR

Volume-matched placebo is a single treatment

Drug: Phase 3; Placebo

Interventions

Phase 2; Low Dose MYOBLOC DRUG

Intramuscular injections on Day 1

Also known as: rimabotulinumtoxinB, botulinum toxin type B

Phase 2; Low Dose MYOBLOC

Phase 2; High Dose MYOBLOC DRUG

Intramuscular injections on Day 1

Also known as: rimabotulinumtoxinB, botulinum toxin type B

Phase 2; High Dose MYOBLOC

Phase 2; Placebo DRUG

Intramuscular injections on Day 1

Also known as: PBO

Phase 2; Placebo

Phase 3; MYOBLOC DRUG

Intramuscular injections on Day 1

Also known as: rimabotulinumtoxinB, botulinum toxin type B

Phase 3; MYOBLOC

Phase 3; Placebo DRUG

Intramuscular injections on Day 1

Also known as: PBO

Phase 3; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Changes to treatment regimen or any new treatment with oral antispasmodics and/or muscle relaxants within 30 days before randomization.
• Initiation of physical and/or occupational therapy \<30 days before randomization. Subjects receiving physical and/or occupational therapy ≥30 days before randomization must be willing to maintain their therapy regimen through Week 4 of the DBP.
• Application of an ankle-foot orthosis (AFO) \<30 days before randomization. Subjects regularly using an AFO ≥30 days before randomization must be willing to maintain use of the AFO through Week 4 of the Double-Blind Period.
• Subjects should not receive nor have any plans to receive any botulinum toxin treatment, other than the study drug (MYOBLOC), from the point informed consent is obtained until participation in the study is complete.
• Severe dysphagia (i.e., inability to swallow liquids, solids or both without choking or medical intervention), or dysphagia with a history of aspiration pneumonia, within 6 months before screening.

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead
• Solstice Neurosciences: collaborator

Study Sites (9)

Rancho Research Institute

Downey, California, 90242, United States

Location

New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

Nova Clinical Research, LLC

Bradenton, Florida, 34209, United States

Location

Idaho Physical Medicine and Rehabilitation

Boise, Idaho, 83706, United States

Location

Coastal Neurology

Port Royal, South Carolina, 29935, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Fakultní nemocnice Brno, Neurologická klinika FN Brno (University Hospital Brno, Department of Neurology)

Brno, Czechia

Location

Centrum pro intervenční terapii motorických poruch, Neurologická klinika, Univerzita Karlova Katerinska

Prague, Czechia

Location

MeSH Terms

Conditions

Muscle Spasticity; Stroke; Brain Injuries, Traumatic; Hemiplegia

Interventions

Clinical Trials, Phase II as Topic; rimabotulinumtoxinB; Clinical Trials, Phase III as Topic

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Paralysis

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Jonathan Rubin, MD,MBA

  Supernus Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 23, 2019
• Study Start: December 17, 2019
• Primary Completion: April 1, 2023
• Study Completion: July 1, 2024
• Last Updated: March 7, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); CZ (2)