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

NCT04815967 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: SN-SPAS-201
• 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 upper limb spasticity in adults followed by an open-label extension safety trial.

Conditions

Spasticity; Cerebrovascular Accident; Multiple Sclerosis; Traumatic Brain Injury; Cervical Spinal Cord Injury; Cerebral Palsy

Keywords

Stroke; Traumatic Brain Injury; Monoplegia; Hemiplegia; Upper limb; Multiple Sclerosis; Cerebral Palsy; Cervical Spinal Cord Injury

Outcome Measures

Primary Outcomes (2)

• Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for tone of the Primary Target Muscle Group (PTMG) [Phase 2 and Phase 3]

  The first co-primary endpoint is the change from baseline in Modified Ashworth Scale (MAS) score for tone of the Primary Target Muscle Group (PTMG) selected for treatment 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

• Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) Scale [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 Modified Ashworth Scale (MAS) for tone in each muscle group selected for treatment [Phase 2 and Phase 3]

  Baseline and Week 4

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

  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 Pain Numeric Rating Scale (Pain-NRS) [Phase 2 and Phase 3]

  Baseline and Week 4

• Effect of MYOBLOC on the Modified Barthel Index (MBI) [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.
• Upper limb spasticity due to stroke, or traumatic brain injury, or spinal cord injury that occurred ≥ 6 months prior to randomization. Eligible subjects may have upper limb monoplegia or hemiplegia. Subjects with cerebral palsy are eligible for study enrollment.
• Modified Ashworth Scale (MAS) scores of ≥2 in at least two muscle groups inclusive of the elbow, wrist, and finger flexors at screening and 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, or triplegia with both upper limbs affected.
• 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 contributes to joint immobility in the affected upper limb.
• Unresolved fracture(s) in the affected upper limb.
• Severe atrophy in the affected upper 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 upper limb within 1 year before randomization.
• Presence of a spinal stimulator or intrathecal baclofen pump that has not been turned off within 30 days prior to screening.
• Changes to treatment regimen or any new treatment with oral antispasmodics and/or muscle relaxants within 30 days prior to 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 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 time that 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.
• Prior surgery to treat spasticity in the affected upper limb (i.e., tendon lengthening or tendon transfer).

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; Multiple Sclerosis; Brain Injuries, Traumatic; Cerebral Palsy; 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; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic; 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: No other parties are masked in the clinical trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Treatment Efficacy and Safety Study of MYOBLOC in the Treatment of Adult Upper Limb Spasticity Followed by an Open-Label Extension, Multiple-Treatment in Safety Study of MYOBLOC

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: March 25, 2021
• Study Start: November 16, 2021
• Primary Completion: July 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

CZ (2); US (7)