MT10109L in the Treatment of Lateral Canthal Lines

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety and efficacy of MT10109L in the treatment of lateral canthal lines (LCL) in participants with moderate to severe LCL.

Official Title
-----------------
A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of MT10109L (NivobotulinumtoxinA) for the Treatment of Lateral Canthal Lines

Conditions
-----------------
Lateral Canthal Lines

Intervention / Treatment
-----------------
* Drug: MT10109L
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria • Female participants must not be pregnant or planning to get pregnant and willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. Exclusion Criteria Known immunization or hypersensitivity to any botulinum toxin serotype. Any medical condition that may put the participant at increased risk with exposure to MT10109L including diagnosed myasthenia gravis, Eaton Lambert syndrome, amyotrophic lateral sclerosis, or any other condition that might interfere with neuromuscular function. History of facial nerve palsy. Any uncontrolled systemic disease. Anticipated need for treatment with botulinum toxin of any serotype for any reason during the study (other than study intervention). Anticipated need for surgery or overnight hospitalization during the study. Prior exposure to botulinum toxin of any serotype for any reason. 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 entry into this study. Females who are pregnant, nursing, or planning a pregnancy during the study. Participants who plan for an extended absence away from the immediate area of the study site that would preclude them from returning for all protocol-specified study visits.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT10109L<br>MT10109L will be injected into the LCL: initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. | Drug: MT10109L<br>* MT10109L will be injected into the LCL.<br>* Other names: NivobotulinumtoxinA;|
| Placebo Comparator: Placebo<br>Placebo will be injected into the LCL: initial double-blind treatment on Day 1. | Drug: Placebo<br>* Placebo will be injected into the LCL.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With a ≥ 2-grade Improvement From Baseline on the Facial Wrinkle Scale With Photonumeric Guide (FWS) According to INVESTIGATOR AND PARTICIPANT Assessments of Lateral Canthal Lines (LCL) Severity at Maximum Smile at Day 30 | The primary efficacy measure is a composite endpoint and a participant is considered responder only if both the investigator and participant independently report a ≥ 2-grade improvement at Day 30 of Double-Blind Period from baseline. Both participant and investigator used FWS to assess GL severity. FWS is 4-grade scale (0 to 3): 0=none, 1=mild, 2=moderate and 3=severe | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Responders for INVESTIGATOR Assessments of Lateral Canthal Lines (LCL) Severity at Maximum Smile Using the Facial Wrinkle Scale (FWS) | The Percentage of Responders for Investigator Assessments of Lateral Canthal Lines (LCL) Severity at Maximum Smile Using the Facial Wrinkle Scale (FWS), where a Responder was defined as Achieving a≥2-grade Improvement from Baseline at Maximum Smile at Day 30. The investigator evaluates the participant's LCL severity using a 4-point scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3=severe. | Day 30 | 
| The Duration of Lateral Canthal Lines (LCL) Treatment in Participants Who Achieved a Rating of ≥ 2 Grade Improvement From Baseline in LCL Severity at Maximum Smile at Day 30 According to Investigator Assessments Using the Facial Wrinkle Scale (FWS) | The investigator evaluates the participant's LCL severity using a 4-grade scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3 = severe using the Facial Wrinkle Scale (FWS). The outcome is measured as median time to loss of treatment effect (i.e., return to moderate or severe LCL severity at maximum smile using the FWS). | Day 1 (first treatment) to Day 180 | 
| The Percentage of Participants Reporting Mostly Satisfied/Very Satisfied on the Facial Line Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 for Lateral Canthal Lines (LCL) | The Satisfaction Question 5 grades facial line treatment satisfaction on a 5-point scale (-2 to 2) where -2=Very dissatisfied and 2=Very satisfied. | Day 60 | 
| The Percentage of Responders for Investigator Assessments of Lateral Canthal Lines (LCL) Severity at Rest Using the Facial Wrinkle Scale (FWS) | The investigator evaluates the participant's LCL severity using a 4-point scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3=severe. The outcome was measured among participants who were at least mild at rest at baseline, where a responder was defined as achieving a >=1-grade improvement from baseline at Day 30. | Day 30 | 
| Number of Patients Who Experienced an Adverse Event (AE) Through the Study Duration | This section focuses primarily on Treatment Emergent Adverse Events(TEAEs), i.e., AEs that started or worsened after the first dose of study intervention (Day 1) until up to 30 days after their last visit or study exit. TEAE's are recorded by the PI and their study team from observations made after treatment administration. The safety analyses were conducted in the Safety population. Unless otherwise noted, safety results refer to TEAEs. All safety analyses were performed with participants analyzed by their actual treatment or regimen received. | AEs that started or worsen after the first dose of study intervention and up to 30 days after their last visit or study exit (Day 360 or early exit) | 
| Mean Change From Baseline in Systolic Blood Pressure (BP) | The outcome reported here is the mean change in Systolic BP from baseline to study exit. | Baseline to Day 360 | 
| Mean Change From Baseline in Diastolic Blood Pressure (BP) | The outcome reported here is the mean change in Diastolic BP from baseline to study exit. | Baseline to Day 360 | 
| Mean Change From Baseline in Pulse Rate | The outcome reported here is the mean change in Pulse Rate from baseline to study exit. | Baseline to Day 360 | 
| Mean Change From Baseline in Respiratory Rate | The outcome reported here is the mean change in Respiratory Rate from baseline to study exit. | Baseline to Day 360 | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - Heart Rate | The outcome reported here is a mean change in mean heart rate from baseline to studyexit | Baseline to Day 360 | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - PR Interval | The outcome reported here is a mean change in PR Interval from baseline to study exit | Baseline to Day 360 | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QRS Duration | The outcome reported here is a mean change in QRS duration from baseline to study exit | Baseline to Day 360 | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QT Interval | The outcome reported here is a mean change in QT Interval from baseline to study exit | Baseline to Day 360 | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcB Interval | The outcome reported here is a mean change in QTcB Interval from baseline to study exit | Baseline to Day 360 | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcF Interval | The outcome reported here is a mean change in QTcF Interval from baseline to study exit | Baseline to Day 360 | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - RR Interval | The outcome reported here is a mean change in RR Interval from baseline to study exit | Baseline to Day 360 | 
| Number of Participants With Binding and Neutralizing Antibodies | Only samples that tested positive in the binding antibody confirmatory assay were evaluated for neutralizing antibodies. The participants with positive neutralizing antibodies are only shown. | Baseline to Day 360 |