Study of Intramuscular Injections of ABBV-950 to Assess Adverse Events and Change in Disease Activity in Adult Participants With Upper Limb Spasticity

Study Overview
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Brief Summary
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Spasticity is often observed as muscle tightness and stiffness in the upper and/or lower limbs. Upper limb spasticity can interfere with joint movement and its severity can range from mild to severe. Common causes of spasticity include cerebral palsy, traumatic brain injury, multiple sclerosis, spinal cord injury, and stroke. This study will assess how safe and effective ABBV-950 is in treating upper limb spasticity in adult post-stroke participants. Adverse events and change in symptoms will be assessed. ABBV-950 in an investigational drug being developed for treating spasticity. This study is conducted in 2 parts. In Part 1, participants are assigned to receive different doses of ABBV-950 or placebo. There is 1 in 4 chance that participants will be assigned to receive placebo. In Part 2, participants will be randomly assigned to receive BOTOX, ABBV-950, or placebo. There is 1 in 5 chance for participants to receive placebo. Approximately 297 adult post-stroke participants with upper limb spasticity will be enrolled at approximately 50 sites in the United States. In Part 1, participants will receive intramuscular (IM) injections of ABBV-950 or placebo on Day 1. In Part 2, participants will receive IM injections of BOTOX, ABBV-950, or placebo on Day 1. All participants will be followed for 24 weeks. There may be higher treatment burden for participants in this trial compared to the standard of care. Participants will attend regular clinic visits during the study. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Efficacy, and Tolerability of ABBV-950 for the Treatment of Upper Limb Spasticity in Adult Post-Stroke Patients

Conditions
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Upper Limb Spasticity

Intervention / Treatment
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* Biological: ABBV-950
* Biological: BOTOX
* Drug: Placebo for ABBV-950


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of upper limb spasticity due to stroke, with most recent stroke occurring at least 12 weeks prior to the Screening visit. Modified Ashworth Scale-Bohannon (MAS-B) score of >= 3 in the wrist flexors, and a score of >= 1+ in the finger flexors and MAS-B score of >= 2 elbow flexors at both Screening and Visit 2 (Baseline). Exclusion Criteria: Additional strokes in the 12 weeks preceding the most recent stroke and in the opinion of the investigator, is not at significant risk of experiencing another stroke during the study period. Spasticity in the contralateral upper limb that requires treatment. Presence of fixed contractures in muscles of wrist, elbow, fingers. Botulinum toxin treatment of any serotype in the 20 weeks prior to Day for upper limb spasticity and in the 12 weeks prior to Day 1 for any indication other than upper limb spasticity. Previous surgical intervention, nerve block, or muscle block for the treatment of spasticity in the study limb in the last 12 months. Injection of corticosteroids or anesthetics in the study limb within 12 weeks. Casting of the upper limbs within 12 weeks. Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, and/or amyotrophic lateral sclerosis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: ABBV-950 Dose A<br>Participants will receive ABBV-Dose A on Day 1. | Biological: ABBV-950<br>* Intramuscular (IM) Injection<br>* Other names: Botulinum toxin type A;|
| Placebo Comparator: Part 1: Placebo for ABBV-950 Dose A<br>Participants will receive placebo for ABBV-950 on Day 1. | Drug: Placebo for ABBV-950<br>* Intramuscular (IM) Injection<br>|
| Experimental: Part 1: ABBV-950 Dose B<br>Participants will receive ABBV-950 Dose B on Day 1. | Biological: ABBV-950<br>* Intramuscular (IM) Injection<br>* Other names: Botulinum toxin type A;|
| Placebo Comparator: Part 1: Placebo for ABBV-950 Dose B<br>Participants will receive placebo for ABBV-950 on Day 1. | Drug: Placebo for ABBV-950<br>* Intramuscular (IM) Injection<br>|
| Experimental: Part 1: ABBV-950 Dose C<br>Participants will receive ABBV-950 Dose C on Day 1. | Biological: ABBV-950<br>* Intramuscular (IM) Injection<br>* Other names: Botulinum toxin type A;|
| Placebo Comparator: Part 1: Placebo for ABBV-950 Dose C<br>Participants will receive placebo for ABBV-950 on Day 1. | Drug: Placebo for ABBV-950<br>* Intramuscular (IM) Injection<br>|
| Active Comparator: Part 2: BOTOX Dose A<br>Participants will receive BOTOX Dose A on Day 1. | Biological: BOTOX<br>* Intramuscular (IM) Injection<br>* Other names: OnabotulinumtoxinA;|
| Experimental: Part 2: ABBV-950 Dose A<br>Participants will receive ABBV-950 Dose A on Day 1. | Biological: ABBV-950<br>* Intramuscular (IM) Injection<br>* Other names: Botulinum toxin type A;|
| Experimental: Part 2: ABBV-950 Dose B<br>Participants will receive ABBV-950 Dose B on Day 1. | Biological: ABBV-950<br>* Intramuscular (IM) Injection<br>* Other names: Botulinum toxin type A;|
| Experimental: Part 2: ABBV-950 Dose C<br>Participants will receive ABBV-950 Dose C on Day 1. | Biological: ABBV-950<br>* Intramuscular (IM) Injection<br>* Other names: Botulinum toxin type A;|
| Placebo Comparator: Part 2: Placebo for ABBV-950<br>Participants will receive placebo for ABBV-950 on Day 1. | Drug: Placebo for ABBV-950<br>* Intramuscular (IM) Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Wrist Modified Ashworth Scale-Bohannon (MAS-B) | MAS-B measures muscle tone based on grading the resistance encountered in a specific muscle group by means of passively moving a limb through its range of motion at a study-specified velocity. Score ranges from 0 (No increase in muscle tone) through 4 (Affected part(s) rigid in flexion or extension). | Up to Week 6 | 
| Number of Participants Experiencing Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician Global Impression of Change (CGI-C) Score | CGI-C is a 9-point rating scale used to measure the clinician's impression of overall treatment response since the first dose of study intervention. CGI-C scores range from -4 = very marked worsening to +4 = very marked improvement. | Up to Week 6 | 
| Change in Clinician Global Impression of Severity (CGI-S) Score | CGI-S is a 5-point rating scale used to measure the clinician's or trained personnel's impression of the current severity of the participant's upper limb spasticity. Scores range from 0 = no spasticity to 4 = very severe. | Up to Week 6 | 
| Percentage of Participants Achieving Wrist MAS-B Responder Status | MAS-B measures muscle tone based on grading the resistance encountered in a specific muscle group by means of passively moving a limb through its range of motion at a study-specified velocity. Score ranges from 0 (No increase in muscle tone) through 4 (Affected part(s) rigid in flexion or extension). Responder is defined as participant with >= 1 grade improvement from baseline. | Up to Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spasticity, Upper Limb Spasticity, Stroke, ABBV-950, Botulinum toxin type A