A Study to Assess the Effectiveness of BOTOX (Botulinum Toxin Type A) Injections for the Change of Masseter Muscle Prominence in Adult Participants

Study Overview
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Brief Summary
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The masseter muscle is one of the muscles in the lower face used for chewing. Prominence of the masseter muscle can appear as a widened and square lower face shape, which is an aesthetic concern for individuals who prefer a narrower and more ovoid lower face shape. Treatments are available for masseter muscle prominice (MMP), but researchers are looking for new non-surgical treatments. This study will assess adverse events and effectiveness of BOTOX in adult participants with MMP. BOTOX is being investigated for the treatment of MMP. Participants are placed in 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is 1 in 4 chance that participants will be assigned to placebo. Around 248 adult participants with MMP will be enrolled in the study at approximately 30 sites in Europe. Participants will receive either BOTOX or Placebo administered as 6 intramuscular injections to the masseter on Day 1. Participants who are eligible for retreatment will be given BOTOX on Day 180 and will be followed for up to 6 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.

Official Title
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BOTOX® (Botulinum Toxin Type A) for the Reduction of Masseter Muscle Prominence: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

Conditions
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Masseter Muscle Prominence

Intervention / Treatment
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* Drug: BOTOX
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index < 30 kg/m^2 using the calculation: BMI = weight (kg)/height (m)^2, rounded to the nearest whole number. Participants meets the following criteria: Bilateral Grade 4 or Grade 5 MMP (identical grades for left and right side of the face), as determined at screening and at the Day 1 visit by the investigator using the MMPS. Bilateral Grade 4 or Grade 5 MMP (identical grades for left and right sides of the face), as determined at the Day 1 visit by the participant using the MMPS-P. MMP grades, as assessed by investigator and participant, do not need to be identical but have to be a minimum of Grade 4 with bilateral symmetry at Day 1. Participants who responded A lot or Extremely bothered by the appearance of their MMP as measured by the Bother Impact Assessment for Masseter Muscle Prominence (BIA-MMP) and attain a total score of ≥ 15 on the Lower Facial Shape Questionnaire - Impact Assessment (LFSQ-IA), determined at the Day 1 visit. Exclusion Criteria: Has current intraoral infection, including infection of the mouth or gums, or facial skin infection requiring medical treatment in the opinion of the investigator. Has weakness of the masseter, pterygoid, or temporalis muscles due to trauma, facial nerve injury, or other condition that could interfere with normal chewing and jaw clenching, as determined by the investigator. Excess lower facial fat, jowling, loose or lax skin in lower face, or parotid gland prominence that could interfere with MMPS or MMPS-P grading, as determined by the investigator. Has medical condition that may put the participant at increased medical risk with exposure to BOTOX, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other condition that might interfere with neuromuscular function. History of dental or surgical procedure for lower facial shaping or masseter muscle reduction. History of any soft tissue fillers in the jawline. Has prior exposure to botulinum toxin of any serotype to any part of the body (not including masseter muscle) within the 3 months prior to Day 1. History of or current TMJD, or presence of signs/symptoms of possible TMJD in the opinion of the investigator.

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: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-Blind Period: Botox<br>Participants will receive 6 intramuscular injections of BOTOX to the masseter on Day 1. | Drug: BOTOX<br>* Intramuscular Injections<br>* Other names: Botulinum Toxin Type A;|
| Placebo Comparator: Double Blind Period: Placebo<br>Participants will receive 6 intramuscular injections of Placebo to the masseter on Day 1. | Drug: Placebo<br>* Intramuscular Injections<br>|
| Experimental: Open-Label Period: Botox<br>Participants who are eligible for retreatment will be given open-label BOTOX on Day 180 and will be followed for up to 6 months | Drug: BOTOX<br>* Intramuscular Injections<br>* Other names: Botulinum Toxin Type A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of 2-grade or more improvement from baseline on the Masseter Muscle Prominence Scale (MMPS) as assessed by the Investigator | The investigator assessed the severity of the participant's MMP using the MMPS 5-point scale where: 1=minimal (best), 2=mild, 3=moderate, 4=marked, and 5=very marked (worst). | Day 90 | 
| Achievement of 2-grade or more improvement from baseline on the Masseter Muscle Prominence Scale - Participant (MMPS-P) as assessed by the Participant | The participant assessed the severity of their MMP using the MMPS-P 5-point scale where: 1=not at all pronounced (best), 2=mildly pronounced, 3=moderately pronounced, 4=pronounced, and 5=very pronounced (worst). | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response of Very Satisfied or Satisfied on the Lower Facial Shape Questionnaire - Treatment Satisfaction Assessment (LFSQ-TXSAT) | The LFSQ-TXSAT measures the participant's satisfaction with the effect of treatment on the appearance of their lower face where 2=Very satisfied, 1=Satisfied, 0=Neither satisfied nor dissatisfied, -1=Dissatisfied, -2=Very dissatisfied. | Day 90 to Day 180 | 
| Response of Not at all bothered or A little bothered on the Bother Impact Assessment for Masseter Muscle Prominence (BIA-MMP) | The BIA-MMP is a single item evaluation of how bothered the participant is by the appearance of their lower face where 0=Not at all bothered, 1=A little bothered, 2=Somewhat bothered, 3=A lot bothered, 4=Extremely bothered. | Day 90 to Day 180 | 
| Change from baseline in lower facial volume (cm^3) | Lower facial volume is calculated from standardized images | Day 90 | 
| Change from baseline in lower facial width (mm) | Lower facial width is calculated from standardized images | Day 90 | 
| Change from baseline in Lower Facial Shape Questionnaire - Impact Assessment (LFSQ-IA) summary score | The LFSQ-IA is a 6-item assessment that measures psychosocial impact of the appearance of the lower face where 0= Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit and 4=Extremely. | Day 90 to Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Masseter Muscle Prominence, BOTOX, Botulinum Toxin Type A