Extension Study of ABP-19000 to Evaluate Safety and Efficacy of Repeat Treatments of ABP-450 in Cervical Dystonia

Study Overview
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Brief Summary
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This Open-label Extension 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 42 sites in the United States from Phase 2 (ABP-19000) and Phase 3 (ABP-19001) trials and 29 sites in Europe from Phase 3 (ABP-19001) trial. Study subjects who had their initial dose of study drug in Phase 2 or Phase 3 trial studies, irrespective of treatment allocation, will be eligible to enroll in this OLE study.

Detailed Description
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This Open-label Extension 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 42 sites in the United States from Phase 2 (ABP-19000) and Phase 3 (ABP-19001) trials and 29 sites in Europe from Phase 3 (ABP-19001) trial. Study subjects who had their initial dose of study drug in Phase 2 or Phase 3 trial studies, irrespective of treatment allocation, will be eligible to enroll in this OLE study. Study subjects will receive a predetermined dose of ABP-450 between the Low Dose and High Dose, based on the investigator's discretion and clinical judgment.

Official Title
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An Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of Repeat 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Qualified for and had their initial dose of study drug in the ABP-19000 or ABP-19001 studies and for whom 8 weeks have elapsed between last treatment in the double-blind study (ie, EOS visit) and first treatment in the ABP-19002 OLE study. Provided written informed consent to being treated for cervical dystonia with ABP-450. Were a male or female patient between 18 and 75 years of age (inclusive) when they entered the ABP-19000 or ABP-19001 studies. Have clinical diagnosis of cervical dystonia and need for injection, as determined by the investigator, with TWSTRS total score ≥20. Entered the ABP-19000 or ABP-19001 study on a stable dose of medications (if any) used for focal dystonia treatment (eg, anticholinergics and benzodiazepines) for ≥3months prior to and expected throughout the duration of the study. 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 tele visits. Exclusion Criteria: Have traumatic torticollis or tardive torticollis. Have predominant retrocollis or anterocollis. Have hypersensitivity to human serum albumin, sucrose, or botulinum toxin type A. Have diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease that might interfere with the study. Have marked limitation on passive range of motion that suggests contractures or other structural abnormality (eg, cervical contractures or cervical spine syndrome). Have 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. Current swallowing disorder of any origin (dysphagia scale ≥3, ie, severe, with swallowing difficulties and requiring a change in diet). Participated in another interventional study during participation in this study. Were a pregnant or lactating female, or female of child-bearing potential not willing to use an acceptable method of contraception (ie, intrauterine device, barrier methods with spermicide, or abstinence). Would not benefit from treatment with ABP-450 for their cervical dystonia, in the investigator's opinion. Viral or other active infection or any medical condition that, in the opinion of the investigator, classifies the patient as unsuitable for participation in the study or patients who do not seem to be in good general health at the time of Day 0 rollover, and prior to any investigational study drug administration.

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
Intervention Model: Sequential Assignment
Interventional Model Description: Approximately 60 subjects from ABP-19000 or ABP-19001 studies, irrespective of treatment allocation, will have the option to continue treatment with ABP-450 via intramuscular injection into affected neck muscles.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABP-450 - Between Low Dose and High Dose<br>ABP-450 Between Low Dose and High Dose - Intramuscular injections into affected neck muscles with investigator's determined dose within the range of low dose and high dose - 4 injection cycles at 3-month intervals. | 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;|

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 ABP-450 between Low Dose and High Dose. | Up to 52 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 of 0 - 85 with a higher score representing a worse outcome. with a higher score representing a worse outcome. | Up to 52 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. This subscale has a scale of 0 - 35 with the higher score representing the greater severity. | Up to 52 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. This subscale has a scale of 0 - 30 with the higher score represents the greater disability. | Up to 52 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. This subscale has a scale of 0 - 20 with the higher score represents the greater disability. | Up to 52 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 with a 1-item scale ranging from much better to much worse with the higher score indicating worsening of symptoms will be assessed by Treatment Group. | Up to 52 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 with a 1-item scale ranging from normal to severely ill with the higher score indicating greater severity in illness will be assessed by Treatment Group. | Up to 52 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. | Up to 52 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. | Up to 52 weeks | 
| Time from the First ABP-450 Dose to the First Visit Without Efficacy | The time from first ABP-450 dose to the first visit (from Week 2) without efficacy with regards to TWSTRS total score ≥20 will be captured. | Up to 12 Weeks |