A Phase 2 Study to Evaluate the Safety and Efficacy of ABP-450 in the Treatment of Cervical Dystonia

Study Overview
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Brief Summary
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This Phase 2 trial will evaluate the safety and efficacy of ABP-450 for the treatment of cervical dystonia in adults. The study will enroll 60 patients across approximately 30 sites in the United States. Study subjects will be divided evenly across a low dose group, a medium dose group, a high dose group, and a placebo group for one treatment cycle.

Detailed Description
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This Phase 2 trial will evaluate the safety and efficacy of ABP-450 for the treatment of cervical dystonia in adults. The study will enroll 60 patients across approximately 30 sites in the United States. Study subjects will be divided evenly across a low dose, a medium dose group, a high dose and placebo group for one treatment cycle.

Official Title
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A Phase 2, Randomized, Double-Blind, Multicenter, Placebo Controlled Study to Evaluate the Safety and Efficacy of Intramuscular ABP-450 (prabotulinumtoxinA) Injection for the Treatment of Cervical Dystonia

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Drug: ABP-450
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients between 18 and 75 years of age (inclusive) A clinical diagnosis of cervical dystonia (ie, spasmodic torticollis) defined by: TWSTRS total score ≥20 TWSTRS severity score ≥10 TWSTRS disability score ≥3 TWSTRS pain score ≥1 On a stable dose of medications (if any) used for focal dystonia treatment (eg, anticholinergics and benzodiazepines) for at least 3 months prior to and expected throughout the study duration For pre-treated patients only: Source documentation (eg, patient history) of the last 2 consecutive injection sessions with a botulinum toxin type A For pre-treated patients only: At least 16 weeks must have passed between the last injection with botulinum toxin for cervical dystonia and baseline treatment (patients can be screened at Week 15 but cannot be enrolled until 16 weeks [for Day 0 injection]) Provided written informed consent to being treated for cervical dystonia with ABP-450 Stated willingness to comply with all study procedures, including attendance at the study center for all study visits as scheduled and have technological capabilities to have televisits Exclusion Criteria: Traumatic torticollis or tardive torticollis Predominant retrocollis or anterocollis Myotomy or denervation surgery in the affected muscles (eg, peripheral denervation and/or spinal cord stimulation) Hypersensitivity to human serum albumin, sucrose, or botulinum toxin type A Previous treatment for cervical dystonia with rimabotulinumtoxin B Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease that might interfere with the trial Current swallowing disorder of any origin (dysphagia scale ≥3, ie, severe, with swallowing difficulties and requiring a change in diet) Marked limitation on passive range of motion that suggests contractures or other structural abnormality, eg, cervical contractures or cervical spine syndrome Treatment with botulinum toxins of any type for any indication other than cervical dystonia within 16 weeks prior to baseline and during the study Medical or psychiatric conditions that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study Participation in another interventional study during participation in this study Pregnant or lactating females, or females of child-bearing potential not willing to use an acceptable method of contraception (ie, intrauterine device, barrier methods with spermicide, or abstinence) For pre-treated patients only: The patient's most recent injection with botulinum toxin exceeding the number of units specified as follows: OnabotulinumtoxinA (BOTOX®): >300 units IncobotulinumtoxinA (Xeomin®): >300 units AbobotulinumtoxinA (Dysport®): >750 units

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Interventional Model Description: Approximately 60 patients will be randomized in a 1:1:1:1 ratio and receive one of the four treatments: ABP-450 low dose, ABP-450 mid dose, ABP-450 high dose, or placebo via intramuscular injection into affected neck muscles.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABP-450 - Low Dose<br>ABP-450 Low Dose - Intramuscular injections into affected neck muscles. | Drug: ABP-450<br>* ABP-450 (prabotulinumtoxinA) contains a 900kDA botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.<br>* Other names: prabotulinumtoxinA;|
| Experimental: ABP-450 - Medium Dose<br>ABP-450 Mid Dose - Intramuscular injections into affected neck muscles. | Drug: ABP-450<br>* ABP-450 (prabotulinumtoxinA) contains a 900kDA botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.<br>* Other names: prabotulinumtoxinA;|
| Experimental: ABP-450 - High Dose<br>ABP-450 High Dose - Intramuscular injections into affected neck muscles. | Drug: ABP-450<br>* ABP-450 (prabotulinumtoxinA) contains a 900kDA botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.<br>* Other names: prabotulinumtoxinA;|
| Placebo Comparator: Placebo<br>Placebo (0.9% saline, sterile, unpreserved, USP/Ph.Eur.) - Intramuscular injections into affected neck muscles. | Drug: Placebo<br>* 0.9% sodium chloride, sterile, unpreserved, USP/Ph.Eur.<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-related Serious Adverse Events | The primary safety endpoint will be the incidence of treatment-related serious adverse events since the start of treatment by Treatment Group when dosed with placebo, ABP-450 (low dose), ABP-450 (mid dose), or ABP-450 (high dose). | Baseline up to 20 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score | The mean change in the total score of the TWSTRS since the start of treatment will be assessed by treatment group. The TWSTRS total score is a summation of the following subscales: Severity scale, Disability scale and Pain scale with a higher score representing a worse outcome. | Baseline up to 20 weeks | 
| Mean Change in the subscale score of severity of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | The mean change in the subscale score of severity of the TWSTRS since the start of treatment will be assessed by Treatment Group. The higher score represents the greater severity. | Baseline up to 20 weeks | 
| Mean Change in the subscale score of disability of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Spasmodic Torticollis Rating Scale (TWSTRS) | The mean change in the subscale score of disability of the TWSTRS since the start of treatment will be assessed by Treatment Group. The higher score represents the greater disability. | Baseline up to 20 weeks | 
| Mean Change in the subscale score of pain of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | The mean change in the subscale score of pain of the TWSTRS since the start of treatment will be assessed by Treatment Group. The higher score represents the greater pain. | Baseline up to 20 weeks | 
| Mean Change in Patient Global Impression of Change (PGI-C) | The mean change in the subject's assessment of the change in clinical status since the start of treatment measured by the Patients' Global Impression of Change (PGI-C) Scale will be assessed by Treatment Group. | Baseline up to 20 weeks | 
| Mean Change in Patient Global Impression of Severity (PGI-S) | The mean change in the subject's assessment of the severity of their condition since the start of treatment measured by the Patients' Global Impression of Severity (PGI-S) Scale will be assessed by Treatment Group. | Baseline up to 20 weeks | 
| Mean Change in Clinical Global Impression of Change (CGI-C) | The mean change from Baseline in the Clinical Global Impression of Change (CGI-C) Score will be assessed by Treatment Group. CGI-C is a clinical assessment with a 7-point scale ranging from very much improved to very much worse. | Baseline up to 20 weeks | 
| Mean Change in Clinical Global Impression of Severity (CGI-S) | The mean change from Baseline in the Clinical Global Impression of Severity (CGI-S) Score will be assessed by Treatment Group. CGI-S is a clinical assessment of the patient's illness severity on a 7-point scale ranging from normal to among the most extremely ill patients. | Baseline up to 20 weeks |