AGN-151586 Dose-Ranging Study for Treatment of Glabellar Lines

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of AGN-151586 over a range of doses for the treatment of moderate to severe glabellar lines (GL).

Official Title
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A Phase 2b Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of AGN-151586 in Participants With Moderate to Severe Glabellar Lines

Conditions
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Glabellar Lines

Intervention / Treatment
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* Drug: AGN-151586
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period (at least 10 weeks after study intervention). Exclusion Criteria: Known immunization or hypersensitivity to any botulinum neurotoxin serotype Any medical condition that may put the participant at increased risk with exposure to AGN-151586, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other condition that might interfere with neuromuscular function Marked facial asymmetry, dermatochalasis, deep dermal scarring, excessively thick sebaceous skin, or the inability to substantially lessen facial lines even by physically spreading them apart, as determined by the investigator Any brow or eyelid ptosis, as determined by the investigator Infection or skin disorder at the injection sites History of facial nerve palsy Any uncontrolled systemic disease Anticipated need for treatment with botulinum neurotoxin of any serotype for any reason during the study (other than study intervention) Anticipated need for surgery or overnight hospitalization during the study Prior periorbital surgery, facial lift (full face or mid-face), thread lift, brow lift, or related procedures (eg, eyelid [blepharoplasty] and/or eyebrow surgery) Prior facial treatment with permanent soft tissue fillers, synthetic implantation (eg, Gore-Tex®), and/or autologous fat transplantation Current enrollment in an investigational drug or device study or participation in such a study within 30 days of Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cohort 1: Placebo<br>Participants received AGN-151586-matching placebo, intramuscular (IM) injections in the glabellar complex on Day 1 in Cohort 1. | Drug: Placebo<br>* Placebo solution for injection.<br>|
| Experimental: Cohort 1: AGN-151586<br>Participants received AGN-151586 lowest dose, IM injections in the glabellar complex on Day 1. | Drug: AGN-151586<br>* AGN-151586 solution for injection.<br>|
| Placebo Comparator: Cohort 2: Placebo<br>Participants received AGN-151586-matching placebo, IM injections in the glabellar complex on Day 1 in Cohort 2. | Drug: Placebo<br>* Placebo solution for injection.<br>|
| Experimental: Cohort 2: AGN-151586<br>Participants received AGN-151586, IM injections in the glabellar complex on Day 1. | Drug: AGN-151586<br>* AGN-151586 solution for injection.<br>|
| Placebo Comparator: Cohort 3: Placebo<br>Participants received AGN-151586-matching placebo, IM injections in the glabellar complex on Day 1 in Cohort 3. | Drug: Placebo<br>* Placebo solution for injection.<br>|
| Experimental: Cohort 3: AGN-151586<br>Participants received AGN-151586, IM injections in the glabellar complex on Day 1. | Drug: AGN-151586<br>* AGN-151586 solution for injection.<br>|
| Placebo Comparator: Cohort 4: Placebo<br>Participants received AGN-151586-matching placebo, IM injections in the glabellar complex on Day 1 in Cohort 4. | Drug: Placebo<br>* Placebo solution for injection.<br>|
| Experimental: Cohort 4: AGN-151586<br>Participants received AGN-151586, IM injections in the glabellar complex on Day 1. | Drug: AGN-151586<br>* AGN-151586 solution for injection.<br>|
| Placebo Comparator: Cohort 5: Placebo<br>Participants received AGN-151586-matching placebo, IM injections in the glabellar complex on Day 1 in Cohort 5. | Drug: Placebo<br>* Placebo solution for injection.<br>|
| Experimental: Cohort 5: AGN-151586<br>Participants received AGN-151586 highest dose, IM injections in the glabellar complex on Day 1. | Drug: AGN-151586<br>* AGN-151586 solution for injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 2-grade Improvement From Baseline on the FWS According to Investigator's Assessment at Any Postintervention Timepoint Through Day 7 | Percentage of participants achieving a ≥ 2-grade improvement from baseline on the FWS according to investigator assessments of GL severity at maximum frown at any postintervention timepoint through Day 7 were reported. Investigators' assessments of the severity of GL at rest and maximum frown using the validated FWS was assessed using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. | Baseline (Day 1) through Day 7 | 
| Number of Participants Who Experience One or More Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. TEAEs were defined as events event began on or after the date and time of the study intervention; or the adverse event was present before the date and time of the study intervention, but increased in severity or became serious on or after the date and time of the study intervention. | From first dose of study drug until the end of study (up to 42 days) | 
| Number of Participants With Potentially Clinically Significant Laboratory Parameters Post Intervention | Potentially clinically significant post intervention laboratory values included hematology, chemistry, and urinalysis as defined in the SAP. | From first dose of study drug until the end of study (up to 42 days) | 
| Number of Participants With Potentially Clinically Significant Vital Signs Post Intervention | Potentially clinically significant post intervention vital sign measurements included systolic and diastolic blood pressure, pulse rate, respiration rate, body temperature as defined in the SAP. | From first dose of study drug until the end of study (up to 42 days) | 
| Number of Participants With Potentially Clinically Significant Electrocardiogram Findings Post Intervention | Potentially clinically significant post intervention values in 12-lead ECG recordings included heart rate and measures PR, QRS, QT and QTcF intervals. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semi-supine or supine position as defined in the SAP. A post-baseline value is considered potentially clinically significant if it meets either the observed-value or the change-from-baseline criteria such as QRS interval observed value: ≥ 150 msec; PR interval observed value: ≥ 250 msec; QTcB observed value: > 500 msec or change from baseline value: increase of > 60 msec; QTcF observed value: > 500 msec or change from baseline value: increase of > 60 msec. | From first dose of study drug until the end of study (up to 42 days) | 
| Number of Participants With Anti-drug Antibodies (ADAs) | Number of participants with positive anti-drug antibodies are reported. Binding and neutralizing anti-bodies are evaluated as anti-drug antibodies. Only participants with positive samples for binding antibodies have been analyzed for presence of neutralizing antibodies. | Up to Day 42 |