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

• ClinicalTrials.gov Identifier: NCT04815967
• Recruitment Status: Not yet recruiting
• First Posted: March 25, 2021
• Last Update Posted: July 15, 2021
• Sponsor: Supernus Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Supernus Pharmaceuticals, Inc.

Study Description

Brief Summary:

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 Safety Study of MYOBLOC®,

Condition or disease	Intervention/treatment	Phase
Spasticity; Cerebrovascular Accident; Multiple Sclerosis; Traumatic Brain Injury; Cervical Spinal Cord Injury; Cerebral Palsy	Drug: rimabotulinumtoxinB; Drug: Placebo	Phase 2; Phase 3

Detailed Description:

Multicenter, randomized, double-blind, placebo-controlled study of the safety and efficacy of a single-dose of MYOBLOC over a 1-year duration in adult subjects with upper limb monoplegia or hemiplegia spasticity due to stroke or TBI, followed by an open-label extension safety study of multiple doses. The primary goal is to assess the efficacy of MYOBLOC versus placebo in the treatment of adult upper limb spasticity. The secondary goals are: to establish a safe and efficacious dose of MYOBLOC (administered intramuscularly as a single total dose, to assess the duration of therapeutic response of MYOBLOC after a single administration, and to evaluate the long-term safety and tolerability of MYOBLOC after multiple administrations at 13-week intervals over a minimum duration of 1 year.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 272 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 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
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: No other parties are masked in the clinical trial.
• Primary Purpose: Treatment
• Official Title: Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Treatment Efficacy and Safety Study of MYOBLOC in Treatment of Adult Upper Limb Spasticity and Open-Label Extension, Multiple-Treatment Safety Study of MYOBLOC
• Estimated Study Start Date: July 30, 2021
• Estimated Primary Completion Date: July 1, 2023
• Estimated Study Completion Date: July 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Experimental: Phase 2: MYOBLOC 10,000 U, IM; Phase 2 will compare the efficacy and safety of 2 doses of MYOBLOC versus volume-matched placebo in the treatment of upper limb spasticity. Ninety subjects will be randomized 1:1:1 to receive a total limb dose of 10,000 Units of MYOBLOC, 15,000 U of MYOBLOC. Provided retreatment criteria has been met, subjects will be eligible to participate in open-label extension.	Drug: rimabotulinumtoxinB; IM injection on Day 1, and Week 13 (±2 weeks); Other Names: MYOBLOC; botulinum toxin type B
Experimental: Experimental: Phase 2: MYOBLOC 15,000 U, IM; Phase 2 will compare the efficacy and safety of 2 doses of MYOBLOC versus volume-matched placebo in the treatment of upper limb spasticity. Ninety subjects will be randomized 1:1:1 to receive a total limb dose of 10,000 Units of MYOBLOC, 15,000 Units of MYOBLOC. Provided retreatment criteria has been met, subjects will be eligible to participate in open-label extension.	Drug: rimabotulinumtoxinB; IM injection on Day 1, and Week 13 (±2 weeks); Other Names: MYOBLOC; botulinum toxin type B
Placebo Comparator: Placebo Comparator: Phase 2: Placebo; Volume-matched placebo via intramuscular (IM) injection into targeted muscles of the affected upper limb.	Drug: Placebo; IM injection on Day 1, and Week 13 (±2 weeks)
Experimental: Experimental: Phase 3 -RP3D; Phase 3 will compare the efficacy and safety of the RP3D of MYOBLOC versus volume-matched placebo in the treatment of upper limb spasticity. Between 60 to 182 subjects will be randomized 1:1 to receive the RP3D of MYOBLOC.	Drug: rimabotulinumtoxinB; IM injection on Day 1, and Week 13 (±2 weeks); Other Names: MYOBLOC; botulinum toxin type B
Placebo Comparator: Placebo Comparator: Phase 3: Placebo; Volume-matched placebo via IM injection into targeted muscles of the affected upper limb.	Drug: Placebo; IM injection on Day 1, and Week 13 (±2 weeks)

Outcome Measures

Primary Outcome Measures :

1. The primary objective of this trial is to assess the efficacy of MYOBLOC versus placebo in the treatment of adult upper limb spasticity. [ Time Frame: One Year ]
   Modified Ashworth Scale (0 equals no increase and four equals affected parts rigid and flexion or extension minimum 0- maximum 4); higher score equals greater resistance) and Clinical Global Impression Scale (Greater score means less improvement)

Secondary Outcome Measures :

1. To establish a dose response between 2 active doses of MYOBLOC versus placebo. [ Time Frame: Approximately 13-week intervals over a minimum duration of 1 year ]
   Patient Global Impression ( Greater score means less improvement)
2. • To assess the duration of therapeutic response after a single administration of MYOBLOC. [ Time Frame: Approximately 13-week intervals over a minimum duration of 1 year ]
   Caregiver Global Impression ( Greater score means less improvement)
3. • To evaluate the long-term safety and tolerability of MYOBLOC after multiple administrations. [ Time Frame: Approximately 13-week intervals over a minimum duration of 1 year ]
   Pain Numeric Rating Scale ( the higher the score the greater the pain - 0 equals no pain and ten equals worse pain imaginable)
4. • To evaluate the long-term safety and tolerability of MYOBLOC after multiple [ Time Frame: Approximately 13-week intervals over a minimum duration of 1 year ]
   Modified Barthel Index ( Minimum zero to 24 unable to perform tasks and needs total assistance maximum score 91-99 which means fully independent slowness in performing tasks

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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; or if unable, the subject's Legally Authorized Representative (LAR) may provide written informed consent.
2. Male or female 18 to 80 years of age, inclusive.
3. Upper limb spasticity due to stroke, traumatic brain injury (TBI), 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.
4. Modified Ashworth Scale (MAS) scores ≥2 in at least two muscle groups inclusive of the elbow, wrist, and finger flexors at screening and baseline.
5. 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.
6. 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:

1. Quadriplegia/tetraplegia or triplegia with both upper limbs affected.
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 (ALS), primary lateral sclerosis (PLS), multiple sclerosis (MS), myasthenia gravis, or muscular dystrophy.
4. 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 upper limb.
5. Unresolved fracture(s) in the affected upper limb.
6. Severe atrophy in the affected upper limb.
7. Known hypersensitivity to botulinum toxins type A or 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) in the affected upper 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 prior to screening.
11. Changes to treatment regimen or any new treatment with oral antispasmodics and/or muscle relaxants within 30 days prior to randomization.
12. 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.
13. Prior botulinum toxin type A (BoNT/A) or B (BoNT/B) treatment in the affected upper limb within 24 weeks before screening. Prior BoNT/A or BoNT/B treatment in areas other than the affected upper limb is not exclusionary but must have occurred at least 12 weeks before screening. Prior toxin exposure must have been well tolerated and without any significant long term side effects in the case of repeated prior exposure.
14. 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.
15. 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.
16. Prior surgery to treat spasticity in the affected upper limb (i.e., tendon lengthening or tendon transfer).
17. Any anticipated or scheduled surgery during the study period, with the exception of dermatological procedures performed under local anesthesia for the purposes of removing precancerous and cancerous lesions.
18. Major surgery within 3 months before screening.
19. Pregnancy or breastfeeding.
20. Females of childbearing potential must agree to practice a medically acceptable method of contraception (e.g., intrauterine device, hormonal contraception started at least one full cycle before study enrollment or barrier method in conjunction with spermicide) for the duration of the study (including 2 months after study completion). For the purposes of this study, all females are considered to be of childbearing potential unless they are confirmed by the Investigator to be post-menopausal (at least 1 year since last menses and laboratory test confirmation), biologically sterile, or surgically sterile (e.g., hysterectomy with bilateral oophorectomy, tubal ligation).
21. History of drug or alcohol abuse within 6 months before screening.
22. Obstructive pulmonary disease with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <70%.
23. Slow vital capacity (SVC) <60% of predicted.
24. Chronic or current use of inhaled corticosteroids.
25. Ventilator dependence (i.e., 24-hour ventilator dependence when intubated, or due to a failure to wean the subject from the ventilator while hospitalized in the intensive care unit or respiratory care center). Subjects who use oxygen on an as needed basis or during sleeping hours only via a nasal cannula are eligible for the study.
26. Infection at the planned sites of injection.
27. Treatment with an investigational drug, device, or biological agent within 30 days before screening.
28. Malignancy diagnosed 3 months before screening.
29. Any other medical illness, condition, or clinical finding that, in the opinion of the Investigator and/or the Sponsor, would put the subject at undue risk.

Contacts and Locations

Contacts

Contact: Najeebah Abdul-Musawir, MD, MBA; 240.403.5571; nabdulmusawir@supernus.com

Contact: Lubna Jamal, MD, MBA; 240.403.5727; ljamal@supernus.com

Sponsors and Collaborators

Supernus Pharmaceuticals, Inc.

Investigators

• Study Chair: Azmi Nasser, PhD; Supernus Pharmaceuticals

More Information

• Responsible Party: Supernus Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04815967
• Other Study ID Numbers: SN -SPAS-201
• First Posted: March 25, 2021
• Last Update Posted: July 15, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No: There is not a plan to make IPD available.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Supernus Pharmaceuticals, Inc.:

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

Additional relevant MeSH terms:

Muscle Spasticity; Multiple Sclerosis; Brain Injuries; Spinal Cord Injuries; Brain Injuries, Traumatic; Cerebral Palsy; Stroke; Sclerosis; Wounds and Injuries; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Spinal Cord Diseases; Brain Damage, Chronic; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases