MT10109L in the Treatment of Glabellar Lines

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of MT10109L in the treatment of glabellar lines (GL) in participants with moderate to severe GL.

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

Conditions
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Glabellar Lines

Intervention / Treatment
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* Drug: MT10109L
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT10109L<br>MT10109L will be injected into the GL: 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 GL.<br>* Other names: NivobotulinumtoxinA;|
| Placebo Comparator: Placebo<br>Placebo will be injected into the GL: initial double-blind treatment on Day 1. | Drug: Placebo<br>* Placebo will be injected into the GL.<br>|

What is the study measuring?
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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 Glabellar Lines (GL) Severity at Maximum Frown 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 and 3=severe. The primary endpoint is achieved and recorded as a count only when BOTH INVESTIGATOR AND PARTICIPANT assess the improvement in FWS from baseline to be ≥ 2-grade improvement. Therefore, the primary endpoint is the proportion/percentage of participants who meet the dual assessment threshold of ≥2-grade improvement from baseline. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Responders for Investigator Assessments of Glabellar Lines (GL) Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS) | The Percentage of Responders for Investigator Assessments of Glabellar Lines (GL) Severity at Maximum Frown Using the Facial Wrinkle Scale (FWS), where a Responder was defined as Achieving a ≥2-grade Improvement from Baseline at Maximum Frown at Day 30 of double-blind period. The investigator evaluates the participant's GL severity using a 4-point scale (0 to 3) where 0=none and 3=severe | Day 30 | 
| The Duration of Glabellar Lines (GL) Treatment in Participants Who Achieved a Rating of ≥ 2-grade Improvement From Baseline in GL Severity at Maximum Frown at Day 30 According to Investigator Assessments Using the Facial Wrinkle Scale (FWS) | The investigator evaluates the participant's GL severity using a 4-grade scale (0 to 3) where 0=none and 3 = severe. The outcome is measured as median time to loss of treatment effect (i.e., return to moderate or severe GL severity at maximum frown 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 Glabellar Lines (GL) | 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 Glabellar Lines (GL) Severity at Rest Using the Facial Wrinkle Scale (FWS). | The outcome was measured among participants who Were rated at least mild at rest at baseline, where a Responder was defined as achieving a ≥1-grade improvement from Baseline at Day 30 of double-blind period. The investigator evaluates the participant's GL severity using a 4-point scale (0 to 3) where 0=none and 3=severe. | 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. The safety analyses were conducted in the Safety population. Unless otherwise noted, safety results refer to TEAEs. | The time frame for AEs is from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit). | 
| Mean Change From Baseline in Vital Signs - Systolic Blood Pressure (BP) | Change from baseline at study exit. | Baseline to Study exit (Day 360 or early exit) | 
| Mean Change From Baseline in Vital Signs - Diastolic Blood Pressure (BP) | Change from baseline at study exit. | Baseline to Study exit (Day 360 or early exit) | 
| Mean Change From Baseline in Vital Signs - Pulse Rate | Change from baseline at study exit. | Baseline to Study exit (Day 360 or early exit) | 
| Mean Change From Baseline in Vital Signs - Respiratory Rate | Change from baseline at study exit. | Baseline to Study exit (Day 360 or early exit) | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - Heart Rate | Change from baseline at study exit. | Baseline to Study Exit (Day 360 or early exit) | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - PR Interval | Change from baseline at study exit. | Baseline to Study Exit (Day 360 or early exit) | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QRS Duration | Change from baseline at study exit. | Baseline to Study Exit (Day 360 or early exit) | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QT Interval | Change from baseline at study exit. | Baseline to Study Exit (Day 360 or early exit) | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcB Interval | Change from baseline at study exit. | Baseline to Study Exit (Day 360 or early exit) | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcF Interval | Change from baseline at study exit. | Baseline to Study Exit (Day 360 or early exit) | 
| Mean Change From Baseline in Electrocardiogram (ECG) Parameters - RR Interval | Change from baseline at study exit. | Baseline to Study Exit (Day 360 or early exit) | 
| 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. | Up to Study Exit (Day 360 or early exit) |