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

Phase 2

Active, not recruiting

• Conditions: Spasticity; Cervical Spinal Cord Injury; Cerebral Palsy; Cerebrovascular Accident; Multiple Sclerosis; Traumatic Brain Injury
• Interventions: Drug: Phase 3; Placebo; Drug: Phase 2; Low Dose MYOBLOC; Drug: Phase 2; High Dose MYOBLOC; Drug: Phase 2; Placebo; Drug: Phase 3; MYOBLOC

• Registration Number: NCT04815967
• Lead Sponsor: Supernus Pharmaceuticals, Inc.

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.

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 upper 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 upper 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 upper limb spasticity.

Study Timeline

• Study First Submitted: 2021-02-11
• Study First Submitted QC: 2021-03-22
• Study First Posted: 2021-03-25
• Study Start: 2021-11-16
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-07
• Primary Completion: 2023-07-01
• Study Completion: 2024-07-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 272

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 3; Placebo	Phase 3; Placebo	Volume-matched placebo is a single treatment
Phase 2; Low Dose MYOBLOC	Phase 2; Low Dose MYOBLOC	Low Dose MYOBLOC is a single treatment and will be compared to volume-matched placebo
Phase 2; High Dose MYOBLOC	Phase 2; High Dose MYOBLOC	High Dose MYOBLOC is a single treatment and will be compared to volume-matched placebo
Phase 2; Placebo	Phase 2; Placebo	Volume-matched placebo is a single treatment
Phase 3; MYOBLOC	Phase 3; MYOBLOC	MYOBLOC is a single treatment and will be compared to volume-matched placebo

Primary Outcome Measures

Name	Time	Method
Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) Scale [Phase 2 and Phase 3]	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.
Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for tone of the Primary Target Muscle Group (PTMG) [Phase 2 and Phase 3]	Baseline and Week 4	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.

Secondary Outcome Measures

Name	Time	Method
Effect of MYOBLOC on the Patient Global Impression of Change (PGI-C) [Phase 2 and Phase 3]	Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit)	An additional secondary endpoint is the Patient Global Impression of Change (PGI-C) score at Weeks 2, 8 and 13 (and, if applicable, at re-evaluation visit) post-injection. The PGI-C scale is a single item patient reported (self) assessment of how much his/her ability to function has improved, worsened or has not changed relative to his/her baseline state prior to treatment (injection). The PGI-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.
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 Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit)	An additional secondary endpoint is the change from baseline in Modified Ashworth Scale (MAS) score for tone in each muscle group selected for treatment at Weeks 2, 8 and 13 (and, if applicable, at re-evaluation visit) 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.
Effect of MYOBLOC on the Modified Barthel Index (MBI) [Phase 2 and Phase 3]	Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit)	An additional secondary endpoint is the change from baseline in the Modified Barthel Index (MBI) score at Weeks 2, 8 and 13 (and, if applicable, at re-evaluation visit) post-injection. The MBI is a 10-item scale self assessment that measures the patient's degree of independence with activities of daily living (bowel control, bladder control, help with grooming, toilet use, feeding, transfers, walking, dressing, climbing stairs, and bathing). An item (activity) is given one of five levels (rating) of dependency ranging from 0 (unable to perform task) to a maximum of 5, 10, or 15 (fully independent). The sum of ratings of the 10 items yields a total score ranging from 0 to 100. A higher change from baseline MBI score (\>0) represents a better outcome.
Effect of MYOBLOC on the Modified Ashworth Scale (MAS) Responder Rate for the Primary Target Muscle Group (PTMG) [Phase 2 and Phase 3]	Baseline and Week 4	An additional secondary endpoint is the Modified Ashworth Scale (MAS) Responder Rate for the Primary Target Muscle Group (PTMG) at Week 4 post-injection. The MAS responder rate is defined as the percent of subjects with ≥1 grade reduction in their change from baseline MAS score for the PTMG at Week 4. Values range from 0 to 100%. A higher percentage represents a greater number of responders.
Effect of MYOBLOC on the Modified Ashworth Scale (MAS) for tone in the Primary Target Muscle Group (PTMG) [Phase 2 and Phase 3]	Baseline and Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit)	An additional secondary endpoint is the change from baseline in Modified Ashworth Scale (MAS) score for tone in the Primary Target Muscle Group (PTMG) at Weeks 2, 8 and 13 (and, if applicable, at re-evaluation visit) 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.
Effect of MYOBLOC on Clinical Global Impression of Change (CGI-C) Scale [Phase 2 and Phase 3]	Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit)	An additional secondary endpoint is the Clinical Global Impression of Change (CGI-C) score in functional ability at Weeks 2, 8, and 13 (and, if applicable, at re-evaluation visit) 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.
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)	An additional secondary endpoint is the Caregiver Global Impression of Change (GGI-C) score at Weeks 2, 8 and 13 (and, if applicable, at re-evaluation visit) post-injection. The GGI-C scale is a single item caregiver assessment on how much the patient's ability to function has improved, worsened or has not changed relative to the patient's baseline state prior to treatment (injection). The GGI-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.
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)	An additional secondary endpoint is the change from baseline in the Pain Numeric Rating Scale (Pain-NRS) score at Weeks 2, 8 and 13 (and, if applicable, at re-evaluation visit) post-injection. The Pain-NRS is a unidimensional measure of pain intensity in adults. It is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of his/her pain. The common format is a horizontal bar or line. Similar to the VAS, the Pain-NRS is anchored by terms describing pain severity extreme on 11-point scale ranging from 0 ("no pain") to 10 ("worse pain imaginable"). A lower change from baseline Pain-NRS score (\<0) represents a better outcome.
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)	An additional secondary efficacy endpoint is the change from baseline in the Clinical Global Impression of Severity (CGI-S) score at Weeks 2, 4, 8 and 13 (and, if applicable, at re-evaluation visit) post-injection. The CGI-S is a single item clinician assessment of the severity of impairment the patient's spasticity has on his or her ability to function based on the clinician's total clinical experience with patients with upper limb spasticity. The CGI-S is rated on a 7-point Likert scale from 1 to 7, where 1=normal; 2=borderline impaired; 3=mildly impaired; 4=moderately impaired; 5=markedly impaired; 6=severely impaired; 7=among the most extremely impaired. A change from baseline CGI-S score \<0 represents a better outcome.
Effect of MYOBLOC on the Patient Global Impression of Severity (PGI-S) [Phase 2 and Phase 3]	Baseline and Weeks 2, 4, 8, and 13 (and, if applicable, at re-evaluation visit)	An additional secondary efficacy endpoint is the change from baseline in the Patient Global Impression of Severity (PGI-S) score at Weeks 2, 4, 8, and 13 (and, if applicable, at re-evaluation visit) post-injection. The PGI-S is a single item patient reported (self) assessment of his/her severity of impairment their spasticity has on his or her ability to function. The PGI-S is rated on a 7-point Likert scale from 1 to 7, where 1=normal; 2=borderline impaired; 3=mildly impaired; 4=moderately impaired; 5=markedly impaired; 6=severely impaired; 7=among the most extremely impaired. A change from baseline PGI-S score \<0 represents a better outcome.
Effect of MYOBLOC on the Caregiver Global Impression of Severity (GGI-S) [Phase 2 and Phase 3]	Baseline and Weeks 2, 4, 8, and 13 (and, if applicable, at re-evaluation visit)	An additional secondary efficacy endpoint is the change from baseline in the Caregiver Global Impression of Severity (GGI-S) score at Weeks 2, 4, 8 and 13 (and, if applicable, at re-evaluation visit) post-injection. The GGI-S is a single item caregiver assessment of the severity of impairment the patient's spasticity has on his or her ability to function. The GGI-S is rated on a 7-point Likert scale from 1 to 7, where 1=normal; 2=borderline impaired; 3=mildly impaired; 4=moderately impaired; 5=markedly impaired; 6=severely impaired; 7=among the most extremely impaired. A change from baseline GGI-S score \<0 represents a better outcome.

Trial Locations

Locations (9)

Centrum pro intervenční terapii motorických poruch, Neurologická klinika, Univerzita Karlova Katerinska; 🇨🇿 Prague, Czechia

Rancho Research Institute; 🇺🇸 Downey, California, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

New England Institute for Clinical Research; 🇺🇸 Stamford, Connecticut, United States

Idaho Physical Medicine and Rehabilitation; 🇺🇸 Boise, Idaho, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Nova Clinical Research, LLC; 🇺🇸 Bradenton, Florida, United States

Coastal Neurology; 🇺🇸 Port Royal, South Carolina, United States

Fakultní nemocnice Brno, Neurologická klinika FN Brno (University Hospital Brno, Department of Neurology); 🇨🇿 Brno, Czechia